The reduction of the metabolyc syndrome in Navarra-Spain (RESMENA-S) study: A multidisciplinary strategy based on chrononutrition and nutritional education, together with dietetic and psychological control
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Abstract
The high prevalence of metabolic syndrome (MS) in Spain requires additional efforts for prevention and treatment.
The study RESMENA-S aims to improve clinical criteria and biomarkers associated with MS though an integral therapy approach.
The study is a randomized prospective parallel design in which is expected to participate a total of 100 individuals. The RESMENA-S group (n = 50) is a personalized weight loss (30% energy restriction) diet, with a macronutrient distribution (carbohydrate / fat / protein) of 40/30/30, high meal frequency (7 / day), low glycemic index/load and high antioxidant capacity as well as a high adherence to the Mediterranean diet. The control group (n = 50) is assigned to a diet with the same energy restriction and based on the American Heart Association pattern. Both experimental groups are under dietary and psychological control during 8 weeks. Likewise, for an additional period of 16 weeks of self-control, is expected that volunteers will follow the same pattern but with no dietary advice.
Anthropometrical data and body composition determinations as well as blood and urine samples are being collected at the beginning and end of each phase. This project is registered at www.clinicaltrials.gov with the number NCT01087086 and count with the Research Ethics Committee of the University of Navarra approval (065/2009).
Intervention trials to promote the adoption of dietary patterns and healthy lifestyle are of great importance to identify the outcomes and nutritional mechanisms that might explain the link between obesity, metabolic syndrome and associated complications.
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... The current study enrolled 66 participants of the RESMENA-S study, which was designed as a randomized, controlled intervention trial to compare the effects of two hypocaloric dietary strategies (American Heart Association and RESMENA) on metabolic syndrome features after a 6-month follow-up. Subjects were assigned (using the "random between 1 and 2" function in the Microsoft Office Excel 2003 software (Microsoft Iberica, Spain) to follow one of the two energy-restricted diets described elsewhere [26]. Both diets have been found to produce similar weight loss and metabolic outcomes, so both dietary groups were merged for the current analyses as statistically designed in other investigations of the RESMENA study [27]. ...
... Both diets have been found to produce similar weight loss and metabolic outcomes, so both dietary groups were merged for the current analyses as statistically designed in other investigations of the RESMENA study [27]. Physical activity was evaluated by a 24 h questionnaire at the beginning and at the end of the study [26]. ...
... A 48-h weighed food record was completed at the beginning and at the end of the study, which was used to evaluate the volunteer's adherence to the prescribed diet. The energy and nutrient content of these questionnaires were determined with the DIAL software (Alce Ingenieria, Madrid, Spain), as described elsewhere [26]. Anthropometric determinations were measured in fasting conditions and following standardized procedures previously reported [28]. ...
Introduction
Previous studies have hypothesized Fibroblast growth factor 21 (FGF-21) as a potential biomarker of the inflammation associated to liver diseases, which is also receiving high attention for its potential application concerning the management of obesity and co-morbidities. This study aimed to analyze the response of FGF-21 after a weight loss intervention and the relationships with other putative inflammatory liver biomarkers.
Material and methods
Sixty-six obese participants from the RESMENA study were evaluated at baseline and after following a 6-months energy restriction treatment. Anthropometrical, body composition by DXA, routine laboratory measurements, which included transaminases and gamma-glutamyl transferase (GGT) were analyzed by standardized methods. Moreover, FGF-21, M30-fragment (M30) and plasminogen activator inhibitor-1 (PAI-I) were analyzed as recognized liver inflammatory related biomarkers with specific ELISA Kits.
Results
Most measurements related with hepatic damage, inflammation and adiposity status improved at the end of the 6-months nutritional intervention. In addition, ΔFGF-21 shifts evidenced statistical relationships with changes in ΔM30, ΔGGT and ΔPAI. The reduction of M30 showed significant associations with changes in transaminases. Furthermore, PAI-I changes were related with ΔM30 and ΔGGT regardless of weight loss. A linear regression model was set up to assess the influence of ΔPAI-I and ΔM30 on the variability of ΔFGF-21 (23.8%) adjusted by weight loss.
Conclusions
These results evidenced interactions of some liver inflammatory mediators, specifically M30 and PAI-I with FGF-21. Thus, more investigation about FGF-21 is required given that this protein could be a biomarker of the obesity-inflammation-liver process.
... The therapeutic strategy mostly promoted to prevent and treat obesity is a combination of diet, lifestyle changes, and exercise. Many studies show how a healthy diet can help lower excess body fat and have a positive impact on individuals suffering from obesity and MetS [5]. In this context, caloric restriction has a positive impact on body weight [6]. ...
... A randomized subsample of 24 participants age 35 to 65 y with central obesity (waist circumference >94 cm in men and >80 cm in women) who were diagnosed with MetS (based on guidelines established by the International Diabetes Federation [5]) were selected from two dietary groups: Control group (based on AHA diet) and RESMENA group (based on the MD). The RESMENA study is a randomized, prospective, parallel design study [5] registered at www.clinicaltrials.gov ...
... A randomized subsample of 24 participants age 35 to 65 y with central obesity (waist circumference >94 cm in men and >80 cm in women) who were diagnosed with MetS (based on guidelines established by the International Diabetes Federation [5]) were selected from two dietary groups: Control group (based on AHA diet) and RESMENA group (based on the MD). The RESMENA study is a randomized, prospective, parallel design study [5] registered at www.clinicaltrials.gov (NCT01087086). ...
Objective
This study aims to analyze the expression pattern of microRNAs (miRNAs) in white blood cells (WBC) in response to two different energy-restricted diets in metabolic syndrome (MS) patients from the RESMENA study.
Methods
A subsample of 24 individuals with MS features from the randomized prospective parallel designed RESMENA study was selected for this analysis. The RESMENA study consisted of two dietary strategies with a 30% energy restriction: RESMENA group, with high meal frequency and high adherence to Mediterranean diet, and Control group, based on the recommendations from the American Heart Association. Anthropometric and biochemical parameters and miRNA expression in WBC by miRNA-seq, were measured before and after 8 weeks of intervention.
Results
A total of 49 miRNAs were differentially expressed after 8 weeks of dietary intervention, 35 from AHA and 14 from RESMENA diet. MiR-410, miR-637, miR-214, and miR-190 evidenced the most significant expression changes due to the weight loss intervention (p<0,01). MiR-2115, miR-587 and miR-96 showed differential expression between the two dietary strategies after 8 weeks of intervention. The expression of several miRNAs was significantly associated with anthropometric and biochemical parameters: miR-410 levels positively correlated with circulating leptin and BMI, while miR-587 expression was associated with VCAM-1.
Conclusion
Different dietary patterns induce specific changes in miRNA expression in WBC. The associations of specific miRNAs with biochemical and anthropometric parameters suggest that these miRNAs might be directly or indirectly involved in the effects of weight loss diets with different food and macronutrient composition and participate in the regulation of metabolic diseases.
... A few national and international centers associated with nutritional education aiming to change dietary patterns have provided a strategic, nutritional and therapeutic intervention according to individuals' diseases and needs. These centers also include lectures and discussion groups to improve patients' clinical and metabolic profiles [7][8][9] . In this context, counseling strategies provided by telephone or internet have been gaining importance in recent years due to their easy access to health information 10,11 . ...
... This may have occurred as a result of the disease diagnostic criterion since the laboratory presentation of dyslipidemia comprises four Table 5. PROCARDIO patient portrait according baseline data for sex, age and adiposity indicators. (33,8) 138,7 (79,2-207,4) Ã 68,7 (26,3) 98,0 (46, 4) 75,7 (22,4) 115 (15,3) 19,0 Ã (15,0-24,0) 18,5 (15,8) 24,0 (15,9-33,0) Ã 19,5 (14,5) 24,0 (17,0-32,0) Ã Ã p < 0,05. † p < 0,001. ...
... This may have occurred as a result of the disease diagnostic criterion since the laboratory presentation of dyslipidemia comprises four Table 5. PROCARDIO patient portrait according baseline data for sex, age and adiposity indicators. (33,8) 138,7 (79,2-207,4) Ã 68,7 (26,3) 98,0 (46, 4) 75,7 (22,4) 115 (15,3) 19,0 Ã (15,0-24,0) 18,5 (15,8) 24,0 (15,9-33,0) Ã 19,5 (14,5) 24,0 (17,0-32,0) Ã Ã p < 0,05. † p < 0,001. ...
Background: Strategies of promotion, prevention and health care of individuals with cardiometabolic risk are necessary to control cardiovascular diseases.
Objective: To describe a study design and present partial results of nutritional counseling in the Cardiovascular Health Care Program (PROCARDIO).
Methods: PROCARDIO is a nutritional intervention program for students and workers or dependents of the Brazilian university academic community who are at risk of or have a cardiovascular disease (Brazilian Registry of Clinical Trials n° RBR-5n4y2g). Patients are submitted to nutritional clinical assessments involving anthropometry, biochemical analysis, sociodemographic and clinical, lifestyle and dietary data. Patients are provided with nutritional counseling, dietetic workshops and educational materials. In addition, nutritional following-ups are performed monthly.
Results: The sample consisted of 296 patients (171 F/125 M, 27-56 years). The prevalence of individuals with excess body weight, dyslipidemia, diabetes and hypertension in the sample were 74.7% (n = 222), 79.1% (n = 235), 18.2% (n = 54) and 25.3% (n = 75), respectively. After three months of nutritional counseling, PROCARDIO users had decreased body fat, waist circumference, fasting blood glucose, total cholesterol and LDL-C (p < 0.05). Specifically, patients with diabetes exhibited reduced glycated hemoglobin concentrations (p < 0.05); those with dyslipidemia showed a reduction in total cholesterol, LDL-C and LDL/HDL (p < 0.05) concentrations; and those with excess body weight reduced waist circumference, waist-to-hip ratio, body fat, uric acid and total cholesterol/HDL-C ratios (p < 0.05).
Conclusion: PROCARDIO patients concluded with a clinical-metabolic improvement regardless of chronic diseases after receiving nutritional counseling, thus highlighting the importance of individual actions and strategies to be based on personalized nutrition for achieving proposed therapeutic targets.
... Anthropometric measurements including weight, height and waist circumference were collected by trained nutritionists using conventional methods [11,12]. Percentage of body fat was obtained by bioelectrical impedance using the BC-418 Segmental Body Composition Analyzer according to manufacturer instructions (Tanita, Tokyo, Japan). ...
... A 4-month nutritional intervention was conducted involving two hypo-energetic diets (30% of energy restriction), which had different macronutrient distribution based on a low-fat (LF) or a moderately high-protein (MHP) dietary program considering previous trials [11,12]. The target macronutrient of the two diets was: LF diet provided 60% of total energy intake from carbohydrates, 18% from proteins, and 22% from lipids; MHP diet supplied 40% of total energy intake from carbohydrates, 30% from proteins, and 30% from lipids. ...
... Participants were randomly assigned to one of the two dietary regimens, and received detailed information from trained nutritionists regarding feeding schedules, portion sizes, and cooking methods. The adherence to the diet was monitored using a 3-dayweighed food record (including 2 weekdays and 1 weekday), which was applied at the 8th week and at the end of the intervention period (16th week) as described elsewhere [11]. Also, during the 4 months of nutritional intervention, nutritionists conducted motivational telephone calls with each participant in order to increase the adherence to the dietary advice based on previous trials [11,12]. ...
Background and aims:
A precise nutrigenetic management of hypercholesterolemia involves the understanding of the interactions between the individual's genotype and dietary intake. The aim of this study was to analyze the response to two dietary energy-restricted interventions on cholesterol changes in carriers of two ADRB2 polymorphisms.
Methods and results:
A 4-month nutritional intervention was conducted involving two different hypo-energetic diets based on low-fat (LF) and moderately high-protein (MHP) dietary patterns. A total of 107 unrelated overweight/obese individuals were genotyped for two ADRB2 non-synonymous polymorphisms: Arg16Gly (rs1042713) and Gln27Glu (rs1042714). Genotyping was performed by next-generation sequencing and haplotypes were phenotypically screened. Anthropometric measurements and the biochemical profile were assessed by conventional methods. Both diets induced cholesterol decreases at the end of both nutritional interventions. Interestingly, phenotypical differences were observed according to the Arg16Gly polymorphism. Within the MHP group, Gly16Gly homozygotes had lower reductions in total cholesterol (-6.5 mg/dL vs. -24.2 mg/dL, p = 0.009), LDL-c levels (-1.4 mg/dL vs. -16.5 mg/dL, p = 0.005), and non-HDL-c (-4.5 mg/dL vs. -21.5 mg/dL, p = 0.008) than Arg16 allele carriers. Conversely, within the LF group, Gly16Gly homozygotes underwent similar falls in total cholesterol (-18.5 mg/dL vs. -18.7 mg/dL, ns), LDL-c levels (-9.7 mg/dL vs. -13.1 mg/dL, ns), and non-HDL-c (-15.3 mg/dL vs. -15.7 mg/dL, ns) than Arg16 allele carriers. The Gln27Glu polymorphism and the Gly16/Glu27 haplotype showed similar, but not greater effects.
Conclusions:
An energy-restricted LF diet could be more beneficial than a MHP diet to reduce serum cholesterol, LDL-c, and non-HDL-c among Gly16Gly genotype carriers. CLINICALTRIALS.GOV: Identifier: NCT02737267.
... A 48-h weighed food record was collected at the beginning and at the end of the study, and was used to assess the volunteer's adherence to the prescribed diet. The energy and nutrient content of these questionnaires were determined using the DIAL software (Alce Ingenieria, Madrid, Spain), as described elsewhere [10]. This is a validated program in Spain, designed with Spanish foods, and provides information regarding grams of insoluble and soluble fiber obtained from the diet, as well as the total fiber supplied by different food groups (fiber from fruits, vegetables, or cereals, separately). ...
... The fatty liver index (FLI) is an algorithm derived from serum TG, BMI, WC, and GGT levels [12][13][14][15], and was validated in a large group of subjects with or without suspected liver disease with A 48-h weighed food record was collected at the beginning and at the end of the study, and was used to assess the volunteer's adherence to the prescribed diet. The energy and nutrient content of these questionnaires were determined using the DIAL software (Alce Ingenieria, Madrid, Spain), as described elsewhere [10]. This is a validated program in Spain, designed with Spanish foods, and provides information regarding grams of insoluble and soluble fiber obtained from the diet, as well as the total fiber supplied by different food groups (fiber from fruits, vegetables, or cereals, separately). ...
... Anthropometric measurements were assessed in fasting conditions following standardized procedures, as previously reported [9]. Body weight, waist circumference (WC), and body composition as assessed by dual-energy X-ray absorptiometry (Lunar Prodigy, software version 6.0, Madison, WI, USA) were examined at baseline and at the end of the intervention using validated protocols [10]. Body mass index (BMI) was calculated as body weight divided by squared height (kg/m 2 ). ...
The prevalence of non-alcoholic-fatty-liver-disease (NAFLD) is associated with obesity, diabetes, and metabolic syndrome (MS). This study aimed to evaluate the influence of two energy-restricted diets on non-invasive markers and scores of liver damage in obese individuals with features of MS after six months of follow-up and to assess the role of fiber content in metabolic outcomes. Seventy obese individuals from the RESMENA (Reduction of Metabolic Syndrome in Navarra) study were evaluated at baseline and after six months of energy-restricted nutritional intervention (American Heart Association (AHA) and RESMENA dietary groups). Dietary records, anthropometrical data, body composition by dual energy X-ray absorptiometry (DXA), and routine laboratory measurements were analyzed by standardized methods. Regarding liver status, cytokeratin-18 fragments and several non-invasive scores of fatty liver were also assessed. The RESMENA strategy was a good and complementary alternative to AHA for the treatment of obesity-related comorbidities. Participants with higher insoluble fiber consumption (≥7.5 g/day) showed improvements in fatty liver index (FLI), hepatic steatosis index (HIS), and NAFLD liver fat score (NAFLD_LFS), while gamma-glutamyl transferase (GGT) and transaminases evidenced significant improvements as a result of fruit fiber consumption (≥8.8 g/day). Remarkably, a regression model evidenced a relationship between liver status and fiber from fruits. These results support the design of dietary patterns based on the consumption of insoluble fiber and fiber from fruits in the context of energy restriction for the management of obese patients suffering fatty liver disease.
... Al aplicar los criterios de inclusión y el rango de la fecha de publicación del 2005 al 2015, quedaron 34 artículos potenciales, de los cuales se analizó el título y resumen de cada uno y se eliminaron 24 que no cumplían con los criterios, por lo que quedaron 10 estudios para el análisis y evaluación en esta revisión (Fig. 1). Estos estudios se realizaron en diferentes países: dos en España [17,22], dos en Italia [24][25], uno en México [18], uno en Finlandia [23], uno en Cuba [21], uno en Brasil [19] y dos en EE UU [20,26]. ...
... El grupo control se caracterizó por un contenido de macronutrientes de 55/30/15 (carbohidratos/lípidos/proteína) distribuidos en 3 a 5 comidas al día. Demostrando con sus resultados que el patrón de dieta mediterránea, así como la reducción energética ocasionan disminución en los valores de presión arterial y obesidad lo cual impacta en la remisión del síndrome metabólico [22]. En el estudio de Parikka et al. (2008), el objetivo fue evaluar los efectos de la intervención en el estilo de vida sobre el síndrome metabólico y sus componentes a través de la orientación de actividad física y el aumento en la ingesta de fibra. ...
... En esta revisión sistemática se analizaron diez estudios prospectivos que mostraron, que tanto la ingesta hipocalórica como la actividad física son eficaces en la disminución de la incidencia y factores del síndrome metabólico. Esto se ve reflejado en dos de los estudios a base de dieta [22,24], dos a base de actividad física [18,20] y seis muestran que una combinación de ambos resulta mayormente beneficioso [17,19,21,23,25,26], como también lo demuestran otros estudios tal es el caso de Grosso et al. [27] y Blackford et al. [28], donde se realizaron intervenciones en individuos con síndrome metabólico y demostraron que la adherencia a una dieta estilo mediterránea y la intervención en el estilo de vida disminuyen el riesgo de desarrollar síndrome metabólico. Así mismo, estudios como el de Babio et al. [29] asocian que la dieta mediterránea disminuye algunos componentes del síndrome metabólico por lo cual se asume que disminuye las posibilidades de desarrollar este síndrome. ...
The purpose of this article was to conduct a systematic review of prospective studies on lifestyle interventions
on patients with metabolic syndrome diagnosed with The National Cholesterol Adult Treatment Panel III, The International Diabetic Federation and The World Heath Organization criteria. We reviewed English and Spanish articles published in databases from 2005 to 2015. In this systematic review 10 studies were analyzed and we found that nutritional intervention
with physical activity had a major benefit to reduce the metabolic syndrome parameters. The major findings of this study demonstrate that this intervention in lifestyle significantly contribute to the reduction of metabolic syndrome and its components, which individually represent themselves as a problem of public health
... Forty white individuals (20 men and 20 women) with a body mass index (BMI) of 35.41 AE 4.42 kg/m 2 , aged 48 AE 10 y, and diagnosed with MetS according to the International Diabetes Federation cutoffs [9] were enrolled in this study. The inclusion and exclusion criteria have been previously reported [10], but it should be pointed out that individuals with presence of psychiatric disturbances, eating disorders, chronic diseases related to the metabolism of nutrients, major body weight changes in the previous 3 mo, and difficulties in changing food habits were excluded. Volunteers were recruited through local newspaper advertisements and the database of Department of Nutrition, Food Science and Physiology, Center for Nutrition Research, University of Navarra, Pamplona, Spain. ...
... Volunteers were recruited through local newspaper advertisements and the database of Department of Nutrition, Food Science and Physiology, Center for Nutrition Research, University of Navarra, Pamplona, Spain. Calculations were based on findings of previous studies [10,11]. The study protocol was performed in accordance with the ethical guidelines of the Declaration of Helsinki, and was approved by the Research Ethics Committee of the University of Navarra (ref. ...
... The research is based on a subsample of the RESMENA-S study [10], a controlled intervention study that aimed to reduce MetS features based on energy restriction over 6 mo [10,11] and with components of the Mediterranean diet to specifically combat MetS features. The complete project is registered at www.clinicaltrials.gov ...
Objectives:
The aim of this study was to evaluate the influence of a dietary strategy for weight loss (the RESMENA [reduction of metabolic syndrome in Navarra, Spain] diet) on the expression of inflammation-related microRNAS (miRNAs) and genes in white blood cells (WBC) from individuals with metabolic syndrome (MetS).
Methods:
The clinical, anthropometric, and biochemical characteristics of 40 individuals with MetS (20 men and 20 women; age: 48.84 ± 10.02 y; body mass index: 35.41 ± 4.42 kg/m(2)) were evaluated before and after an 8-wk hypocaloric diet based on the Mediterranean dietary pattern. Nutrient intake was assessed with a food frequency questionnaire and 48-h weighed food records. Total RNA was isolated from WBC and the expression of some inflammation-related miRNAs and mRNAs (IL-6, TNF-α, ICAM-1, IL-18, SERPINE1, VCAM-1, GAPDH) was assessed by quantitative polymerase chain reaction.
Results:
The RESMENA nutritional intervention improved most anthropometric and biochemical features. The expression of miR-155-3p was decreased in WBC, whereas Let-7b was strongly upregulated as a consequence of the dietary treatment. However, they were not correlated with the expression of the proinflammatory genes in the same cells. The changes in the expression of let-7b, miR-125b, miR-130a, miR-132-3p, and miR-422b were significantly associated with changes in diet quality when assessed by the Healthy Eating Index. Moreover, low consumption of lipids and saturated fat (g/d) were associated with higher expression of let-7b after the nutritional intervention.
Conclusions:
The Mediterranean-based nutritional intervention was able to induce changes in the expression of let-7b and miR-155-3p in WBC from patients with MetS after 8 wk. Moreover, the quality of the diet has an important effect on the miRNAs expression changes. These results should be highlighted because these miRNAs have been associated with inflammatory gene regulation and important human diseases.
... Convencional therapy includes lifestyle changes (hypocaloric diets and physical activity promotion), which are the first options for a successful short-term weight loss [4]. The reduction of the metabolic syndrome in Navarra-Spain (RESMENA) diet has shown beneficial anti-inflammatory and/or antioxidant effects for obesity, diabetes, and dyslipidemia [5,6]. However, for severe obese individuals, the convencional therapy may not achieve great long-term benefits [4,7]. ...
... This study was conducted in three groups of women of 35-65 years old: 1. control group (n=9), normal weight individuals (BMI from 18.5 to 24.9 kg/m 2 ) of a hospital of Brazil; 2. energy restriction group (ER, n=22), obese patients (BMI> 35 kg/m 2 ) from a subsample of the RESMENA project, a randomized control trial conducted in Spanish individuals [5,31]; and 3. bariatric surgery group (BS, n=14), obese patients (BMI>35 kg/m 2 ) underwent a hypocaloric dietary treatment followed by bariatric surgery (performed by Roux-en-Y gastric bypass) in a hospital of Brazil. The participants who did not follow the energy-restricted dietary protocol, who presented modifications in the standard surgical technique, and pregnant and lactating women were excluded from the study. ...
... The first 2 months consisted of a controlled intervention period and were followed by a 4-month self-control phase. The diet was designed to achieve a daily caloric restriction of 30 % of the subject's total energy baseline needs and contained 40-55 % of energy as carbohydrates, 30 % as lipids, and 15-30 % as proteins [5,32]. The dietary records analyzed using the DIAL software (Alce Ingenieria, Madrid, Spain) showed a high adherence to the dietary strategy at the end of the study, as described previosly [33]. ...
Weight loss can be influenced by genetic factors and epigenetic mechanisms that participate in the regulation of body weight. This study aimed to investigate whether the weight loss induced by two different obesity treatments (energy restriction or bariatric surgery) may affect global DNA methylation (LINE-1) and hydroxymethylation profile, as well as the methylation patterns in inflammatory genes.
This study encompassed women from three differents groups: 1. control group (n = 9), normal weight individuals; 2. energy restriction group (n = 22), obese patients following an energy-restricted Mediterranean-based dietary treatment (RESMENA); and 3. bariatric surgery group (n = 14), obese patients underwent a hypocaloric diet followed by bariatric surgery. Anthropometric measurements and 12-h fasting blood samples were collected before the interventions and after 6 months. Lipid and glucose biomarkers, global hydroxymethylation (by ELISA), LINE-1, SERPINE-1, and IL-6 (by MS-HRM) methylation levels were assessed in all participants.
Baseline LINE-1 methylation was associated with serum glucose levels whereas baseline hydroxymethylation was associated with BMI, waist circumference, total cholesterol, and triglycerides. LINE-1 and SERPINE-1 methylation levels did not change after weight loss, whereas IL-6 methylation increased after energy restriction and decreased in the bariatric surgery group. An association between SERPINE-1 methylation and weight loss responses was found.
Global DNA methylation and hydroxymethylation might be biomarkers for obesity and associated comorbidities. Depending on the obesity treatment (diet or surgery), the DNA methylation patterns behave differently. Baseline SERPINE-1 methylation may be a predictor of weight loss values after bariatric surgery.
... This cross-sectional study randomly enrolled 47 adults from the RESMENA-S (MEtabolic Syndrome REduction in NAvarra-Spain) trial [22]. Subjects presented obesity determined by a BMI higher than 30 kg/m 2 as well as metabolic syndrome features [22]. ...
... This cross-sectional study randomly enrolled 47 adults from the RESMENA-S (MEtabolic Syndrome REduction in NAvarra-Spain) trial [22]. Subjects presented obesity determined by a BMI higher than 30 kg/m 2 as well as metabolic syndrome features [22]. The protocol of the study was previously approved by the Research Ethics Committee of the University of Navarra (065/2009) and in accordance with the ethical principles of the 2008 Declaration of Helsinki. ...
Folate deficiency has been putatively implicated in the onset of diverse metabolic abnormalities, including insulin resistance, by altering epigenetic processes on key regulatory genes. The calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) is involved in the regulation of critical metabolic processes such as adiposity and glucose homeostasis. This study hypothesized associations between low folate intakes and lower methylation levels of the CAMKK2 gene, with the presence of metabolic alterations in subjects with obesity. A cross-sectional ancillary study was conducted in obese subjects (n = 47) from the RESMENA study (Spain). Fat mass was measured by dual-energy x-ray absorptiometry. Dietary intake and metabolic profile were assessed by validated methods. DNA methylation and gene expression in peripheral white blood cells were analyzed by microarray approaches. A total of 51 cytosine-phosphate-guanine sites were associated with folate intake (false discovery rate values < 0.0001), including one located in the 5′ untranslated region of the CAMKK2 gene (Illumina ID, cg16942632), which was selected and separately analyzed. Subjects with total folate intake lower than 300 μg/d showed more fat mass (especially trunk fat), as well as statistically higher levels of glucose, insulin, homeostatic model assessment–insulin resistance (HOMA-IR) index, cortisol, and plasminogen activator inhibitor-1 than those consuming at least or more than 300 μg/d. Of note, folate deficiency was related to lower CAMKK2 methylation. Interestingly, CAMKK2 methylation negatively correlated with the HOMA-IR index. Furthermore, CAMKK2 expression directly correlated with HOMA-IR values. In summary, this study suggests associations between low folate intakes, lower CAMKK2 gene methylation, and insulin resistance in obese individuals.
... general (p<0.001) and mental health (p=0.027), and vitality (p=0.008); with decrement in body weight and WC even sustaining after intervention. Another ongoing trial in Spain is being carried out to lessen the incidence of MetS, which is apparently on the rise [86]. The reduction of the metabolic syndrome in Navarra-Spain (RESMENA-S) study is a randomized prospective parallel design (n=50) encompassing personalized weight loss (30% energy restriction) diet, with a macronutrient distribution (carbohydrate/fat/protein) of 40/30/30, high meal frequency (7/day), low glycemic index/load and high antioxidant capacity as well as a high adherence to the MeD aimed to lower the incidence of the syndrome [86]. ...
... Another ongoing trial in Spain is being carried out to lessen the incidence of MetS, which is apparently on the rise [86]. The reduction of the metabolic syndrome in Navarra-Spain (RESMENA-S) study is a randomized prospective parallel design (n=50) encompassing personalized weight loss (30% energy restriction) diet, with a macronutrient distribution (carbohydrate/fat/protein) of 40/30/30, high meal frequency (7/day), low glycemic index/load and high antioxidant capacity as well as a high adherence to the MeD aimed to lower the incidence of the syndrome [86]. Considering effectiveness of specific food items in MetS reduction, consumption of boiled artichoke meal had no beneficial effect in patients (n=19) with MetS in a RCT which was undertaken to ascertain if artichoke could be beneficial in lowering the post -prandial glucose levels and insulin levels in MetS patients [87]. ...
The emergence of modernization coupled with sedentary lifestyle has resulted in the shift from the prevalence of diseases only due to under nutrition, to those caused by over nutrition. The augmentation of non-communicable diseases, thus, imposes double burden of disease, impeding the health of a nation. This upsurge has led to increase in prevalence and incidence of Metabolic syndrome which is a cluster of inter-related factors characterized by high fasting blood glucose, increased level of triglycerides, low levels of high density cholesterol, elevated blood pressure and abdominal obesity. The best way to combat this syndrome is to reduce the atherosclerotic risk, which can be carried out by modification in the diet and lifestyle – the first line of treatment of the syndrome. Thus, the present review was undertaken to understand the already existing as well as the current scenario specifically regarding the dietary and lifestyle interventions being carried out to overcome Metabolic syndrome. Of the randomized control trials reviewed, all except one reported improvement in Metabolic syndrome following intervention in diet and/or lifestyle modification either in certain components or overall syndrome within a period of 2 weeks–1 year. These interventions to alter diet and lifestyle focus on weight reduction, promotion of regular physical activity, reduction of substance abuse, effectiveness of specific food items along with regulation of genes and various inflammatory markers. They have the potential to succeed only if they are executed early, and thus, offer enough evidence to develop appropriate public policies. However, the issue that is of utmost significance is of sustainability and compliance, which eventually decides the long-term success or failure of an intervention.http://dx.doi.org/10.7175/rhc.v4i4.667
... The current analysis was conducted within a subsample of 48 obese adults (48 ± 10 years old; BMI 36.2 ± 3.8 kg/m 2 ; 46.8% female) that participated in the RESMENA (Metabolic Syndrome Reduction in Navarra) project which is a randomized controlled trial [62], and 25 subjects from the OBEPALIP study [63], which consisted on healthy women with an age range between 21 and 45 years old and a BMI between 27.5 and 36.40 kg/m 2 . The metabolic syndrome was diagnosed following the ATP III criteria [64]. ...
... Anthropometric measurements (body weight, height and waist circumference) were conducted according to validated protocols, as previously described [62,63]. In order to evaluate HRO, the pooled population was assigned to two groups according to BMI classification and risk of obesity-related health problems [65]: "Low HRO" (Overweight (BMI: 25.0-29.9 ...
The aim of this study was to evaluate whether genome-wide levels of DNA methylation are associated with age and the health risks of obesity (HRO); defined according to BMI categories as "Low HRO" (overweight and class 1 obesity) versus "High HRO" (class 2 and class 3 obesity). Anthropometric measurements were assessed in a subsample of 48 volunteers from the Metabolic Syndrome Reduction in Navarra (RESMENA) study and 24 women from another independent study, Effects of Lipoic Acid and Eicosapentaenoic Acid in Human Obesity (OBEPALIP study). In the pooled population; the methylation levels of 55 CpG sites were significantly associated with age after Benjamini-Hochberg correction. In addition, DNA methylation of three CpG sites located in ELOVL2; HOXC4 and PI4KB were further negatively associated with their mRNA levels. Although no differentially methylated CpG sites were identified in relation to HRO after multiple testing correction; several nominally significant CpG sites were identified in genes related to insulin signaling; energy and lipid metabolism. Moreover, statistically significant associations between BMI or mRNA levels and two HRO-related CpG sites located in GPR133 and ITGB5 are reported. As a conclusion, these findings from two Spanish cohorts add knowledge about the important role of DNA methylation in the age-related regulation of gene expression. In addition; a relevant influence of age on DNA methylation in white blood cells was found, as well as, on a trend level, novel associations between DNA methylation and obesity.
... Mediterranean diet high meal frequency group (MD-HMF): participants followed a Mediterranean diet that had previously been shown to decrease fat mass and total weight and improve oxidative status in subjects with metabolic syndrome [16,17]. This diet is characterized by a macronutrient distribution of 40 to 45% carbohydrates (50 to 70% of carbohydrates should be low-glycaemic and high-fiber), 30 to 35% fat, and 25% protein. ...
... Mediterranean diet high meal frequency group (MD-HMF): participants followed a Mediterranean diet that had previously been shown to decrease fat mass and total weight and improve oxidative status in subjects with metabolic syndrome [16,17]. This diet is characterized by a macronutrient distribution of 40 to 45% carbohydrates (50 to 70% of carbohydrates should be low-glycaemic and high-fiber), 30 to 35% fat, and 25% protein. ...
Non-alcoholic fatty liver disease (NAFLD) shows liver fat depots without alcohol consumption. NAFLD does not have specific drug therapies, with a healthy lifestyle and weight loss being the main approaches to prevent and treat NAFLD. The aim was to assess the antioxidant and pro-inflammatory state in patients with NAFLD after 12-month-lifestyle intervention depending on the change in adherence to a Mediterranean diet (AMD). Antioxidant and inflammatory biomarkers were measured in 67 adults (aged 40-60 years old) diagnosed with NAFLD. Anthropo-metric parameters and dietary intake were measured by a validated semi-quantitative 143-item food frequency questionnaire. The nutritional intervention improved anthropometric and biochemical parameters after a 12-month follow-up. However, decreases in alanine aminotransferase (ALT) and C reactive protein (CRP) were higher in participants with high AMD, which also showed higher improvement in physical fitness (Chester step test) and intrahepatic fat contents. The intervention reduced plasma levels of malondialdehyde, myeloperoxidase, zonulin, and omentin, and increased resolvin D1 (RvD1), whereas the decrease in leptin, ectodysplasin-A (EDA), cytokeratin-18 (CK-18), interleukin-1ra (IL-1ra) and endotoxin was only significant in participants with higher AMD. The current study showed that a one-year nutritional intervention improved main NAFLD features such as body mass index, IFC, liver enzymes, and prooxidant and proinflammatory status. There was also a decrease in the concentration of plasmatic endotoxin, suggesting an improvement in intestinal permeability. These health benefits were more evident in participants that improved AMD to a greater extent. The trial was registered at ClinicalTrials.gov with registry number NCT04442620.
... Mediterranean diet high meal frequency (MD-HMF) group: This group was instructed to follow a Mediterranean diet characterized by a distribution of macronutrients of 40-45% carbohydrates (50-70% of carbohydrates should be low glycemic and rich in fiber), 30-35% fat, and 25% protein. This dietary pattern was previously observed to decrease fat mass and overall weight and improve the oxidative status in subjects with metabolic syndrome [32,33]. Total daily caloric intake was distributed over seven meals, with the highest calorie meals eaten early during the morning. ...
Non-alcoholic fatty liver disease (NAFLD) is a disorder characterized by the excessive accumulation of lipids in the liver parenchyma. To date, there is no effective pharmacological treatment against NAFLD. Objective: To assess the relationship between the improvement of the intrahepatic fat content (IFC) in patients with NAFLD and metabolic syndrome and biomarkers of oxidative stress and inflammation after 6 months of lifestyle intervention. Patients diagnosed with NAFLD (n = 60 adults; 40–60 years old) residing in the Balearic Islands, Spain, were distributed in tertiles attending the improvement of IFC calculated by magnetic resonance imaging (MRI). Anthropometrics, blood pressure, maximal oxygen uptake, and pro/antioxidant and inflammatory biomarkers were determined in plasma before and after the lifestyle intervention. The improvement in IFC levels was higher in tertile 3 with respect to tertiles 2 and 1. The greatest improvement in IFC is related to cardiorespiratory fitness and adherence to the Mediterranean diet (ADM). Higher reductions in weight, body mass index (BMI), and alanine aminotransferase (ALT) were observed in tertile 3 with respect to tertile 1 after 6 months of intervention. The improvement in catalase, irisin, and cytokeratin 18 plasma levels were higher in tertile 3, whereas no differences were observed in superoxide dismutase activity. Malondialdehyde and protein carbonyl levels, as biomarkers of oxidative damage, remained unchanged in all groups. The present data show that the reduction of IFC is associated with an improvement in pro/antioxidant and pro-inflammatory status and a better cardiorespiratory fitness in NAFLD patients.
... Patients allocated this treatment were advised to consume 7 meals a day, gradually reducing the caloric content at each main meal, with the highest calorie meals to be consumed early during the day (breakfast, lunch, dinner and two snacks in the morning and two snacks in the afternoon). Moreover, this diet was previously observed to reduce fat mass and overall weight and improve general oxidative stress in patients with metabolic syndrome [15], providing high Total Antioxidant Capacity (TAC), and focused on the chronological distribution of meals, as factors such as meal frequency and distribution could aid in reducing the feeling of hunger, thus improving compliance to an energy-restricted dietary regime [16]. Additionally, with the previous group, subjects were instructed to accumulate a minimum of 10,000 steps a day also recorded by a personal pedometer [17]. ...
Background:
Adults with fatty liver present unusual glycaemia and lipid metabolism; as a result, non-alcoholic fatty liver disease (NAFLD) is now considered as part of the metabolic syndrome (MetS).
Objective:
To assess the 6- and 12-month effects of customized hypocaloric dietary and enhanced physical activity intervention on intrahepatic fat contents and progression of NAFLD, in patients with MetS.
Design:
Cross-sectional study in 155 participants (40-60 years old) from Balearic Islands and Navarra (Spain) with a diagnosis of NAFLD and MetS, and BMI (body mass index) between 27 and 40 kg/m2; patients were randomized in a 1:1:1 ratio to either Conventional Diet, Mediterranean diet (MD)-high meal frequency, and MD-physical activity groups.
Methods:
Dietary intake was assessed using a validated food frequency questionnaire. Adherence to Mediterranean diet, anthropometrics, physical activity, and biochemical parameters (fasting glucose, glycated hemoglobin, bilirubin, aspartate aminotransferase, alanine aminotransferase-ALT-, gamma-glutamyl transferase, uric acid, urea, creatinine, albumin, total cholesterol, high-density lipoprotein cholesterol-HDL-cholesterol-, and triglycerides) were also assessed.
Results:
Subjects with NAFLD and MetS had reduced intrahepatic fat contents, and liver stiffness, despite the intervention the participants went through. All participants ameliorated BMI, insulin, Hb1Ac, diastolic blood pressure, HDL-cholesterol, and ALT, and improved consumption of total energy, fish, and legumes. Participants in the MD-HMF group improved waist circumference.
Conclusions:
Customized hypocaloric dietary and enhanced physical activity interventions may be useful to ameliorate NAFLD.
... Body composition analysis, showing the proportion of fat and non-fat mass in the body, was assessed by dualenergy X-ray absorptiometry (Hologic QDR Discovery DXA (with inner-core™ visceral fat assessment)) in accordance with validated protocols [18]. VAT was calculated automatically using dual-energy X-ray absorptiometry in both grams and cm 3 . ...
AimTo explore the association of visceral adipose tissue (VAT) area and non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM).Methods
This was a cross-sectional study comprising 100 patients with T2DM and 100 non-T2DM individuals, matched for age, sex, and body mass index (BMI). Transient elastography was used to assess hepatic steatosis and liver stiffness measurements (LSM). Controlled attenuation parameter (CAP) was used to quantify hepatic steatosis. To distinguish grades of hepatic steatosis, cutoff values were as follows: S1 ≥ 302, S2 ≥ 331, and S3 ≥ 337 dB/m. Moreover, VAT area was measured by dual-energy X-ray absorptiometry in accordance with validated protocols.ResultsCAP score was significantly higher in participants with T2DM (294.61 ± 3.82 vs. 269.86 ± 3.86 dB/ m; P < 0.001). Furthermore, 42% of participants with T2DM had hepatic steatosis (S > S1: 302 dB/m), while this figure was 26% in non-T2DM group (P < 0.003). The mean liver stiffness measurement was also significantly higher in patients with T2DM (5.53 vs. 4.79 kPa; P < 0.001). VAT area was greater in patients with T2DM compared to non-T2DM individuals: 163.79 ± 47.98 cm2 versus 147.49 ± 39.09 cm2, P = 0.009. However, total and truncal fat mass were not different between the two groups. Age, BMI, waist circumference, ALT, CAP, and LSM were significantly associated with VAT area. BMI and VAT area were the important determinants of steatosis in both groups of participants with and without T2DM. Moreover, the VAT area was associated with the severity of hepatic steatosis and liver stiffness, independent of anthropometric measures of obesity.ConclusionVAT area is a major determinant of the severity of hepatic steatosis and liver stiffness in patient with T2DM.
... Anthropometric measurements such as height (cm) and body weight (kg) were collected in the fasting state by trained nutritionists following validated procedures [19]. Body mass index (BMI) was calculated as the ratio between weight and squared height (kg/m 2 ), and, according to the WHO (World Health Organization) standards, the volunteers were classified as normal weight when BMI was 18.5-24.9 ...
The MD (Mediterranean diet) is recognized as one of the healthiest diets worldwide and is associated with the prevention of cardiovascular and metabolic diseases. Dietary habits are considered one of the strongest modulators of gut microbiota, which seem to play a significant role in health status of the host. The purpose of the present study was to evaluate interactive associations between gut microbiota composition and habitual dietary intake in 360 Spanish adults from the Obekit cohort (normal weight, overweight, and obese participants). Dietary intake and adherence to the MD tests were administered and fecal samples were collected from each participant. Fecal 16S rRNA (ribosomal Ribonucleic Acid) gene sequencing was performed and checked against the dietary habits. MetagenomeSeq was the statistical tool applied to analyze data at the species taxonomic level. Results from this study identified several beneficial bacteria that were more abundant in the individuals with higher adherence to the MD. Bifidobacterium animalis was the species with the strongest association with the MD. Some SCFA (Short Chain Fatty Acids) -producing bacteria were also associated with MD. In conclusion, this study showed that MD, fiber, legumes, vegetable, fruit, and nut intake are associated with an increase in butyrate-producing taxa such as Roseburia faecis, Ruminococcus bromii, and Oscillospira (Flavonifractor) plautii.
... (2) The Mediterranean Diet-high meal frequency (MD-HMF) group, which was instructed to adhere to a Mediterranean Diet based on a distribution of macronutrients of 30%-35% fat (mainly mono-and poly-unsaturated fatty acids from extra virgin olive oil, nuts, and omega-3 containing foods), 25% protein (mainly from vegetable sources), and 40%-45% carbohydrates (50%-70% of the total carbohydrate intake should low on glycaemic index and rich in fiber). This diet was previously observed to reduce fat mass and overall weight and improve general oxidative stress in patients with the metabolic syndrome [16], providing high Total Antioxidant Capacity (TAC), and focused on the chronological distribution of meals, as factors, such as meal frequency and distribution could aid in reducing the feeling of hunger, thus improving compliance to an energy restricted dietary regime [17]. The total daily caloric intake of this diet was distributed over seven meals, with the highest calorie meals to be consumed early during the day. ...
To assess the efficacy of three lifestyle interventions on the reduction of liver fat content and metabolic syndrome (MetS), and whether such reductions would influence renal outcomes, we conducted a randomized controlled trial on 128 participants with MetS and non-alcoholic fatty liver disease (NAFLD), as well as available data on estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatine ratio (UACR). Patients were randomized in 1:1:1 ratio to either Conventional Diet, Mediterranean diet (MD)–high meal frequency, and MD–physical activity groups. Each intervention aimed at reducing caloric intake by 25%–30% of baseline intake and increase energy expenditure by 400 kcal/70 kg. Patients attended regular visits and were followed-up for 6 months. Increased albuminuria was present in 13.3% of patients, while 32.8% showed hyperfiltration. UACR reduction was associated with higher levels of UACR at baseline but not with changes in liver fat. eGFR decreased in patients presenting hyperfiltration at baseline and was associated with reduction in liver fat and insulin resistance, as well as with increase in energy expenditure (R2 = 0.248, p = 0.006). No significant differences were observed between the three treatment groups. In patients with NAFLD and MetS, energy expenditure significantly reduced hepatic fat accumulation and insulin resistance, which reduced glomerular hyperfiltration. Increased albuminuria was reduced, but it was not associated with reduced liver fat.
... Anthropometric measurements (body weight, height, and waist circumference), body composition (DXA, Lunar iDXA, encore 14.5, Madison, WI, USA), and blood pressure (Intelli Sense. M6, OMRON Healthcare, Hoofddorp, The Netherlands) were determined in fasting state following standardized procedures [22]. BMI was calculated as weight (kg) divided by the square of height (m). ...
The identification of affordable noninvasive biomarkers for the diagnosis and characterization of nonalcoholic fatty liver disease (NAFLD) is a major challenge for the research community. This study aimed to explore the usefulness of ferritin as a proxy biomarker of NAFLD condition, alone or in combination with other routine biochemical parameters. Subjects with overweight/obesity and ultrasound-confirmed liver steatosis (n = 112) from the Fatty Liver in Obesity (FLiO) study were assessed. The hepatic evaluation considered magnetic resonance imaging, ultrasonography, and credited routine blood liver biomarkers. Anthropometry and body composition, dietary intake (by means of a validated 137-item food frequency questionnaire), and specific biochemical markers were also determined. Serum ferritin levels were analyzed using a chemiluminescent microparticle immunoassay kit. Lower serum ferritin concentrations were associated with general better liver health and nutritional status. The evaluation of ferritin as a surrogate of liver damage by means of quantile regression analyses showed a positive association with alanine aminotransferase (ALT) (β = 19.21; p ≤ 0.001), liver fat content (β = 8.70; p = 0.008), and hepatic iron (β = 3.76; p ≤ 0.001), after adjusting for potential confounders. In receiver operating characteristic (ROC) analyses, the panel combination of blood ferritin, glucose, and ALT showed the best prediction for liver fat mass (area under the curve (AUC) 0.82). A combination of ferritin and ALT showed the higher predictive ability for estimating liver iron content (AUC 0.73). This investigation demonstrated the association of serum ferritin with liver health as well as with glucose and lipid metabolism markers in subjects with NAFLD. Current findings led to the identification of ferritin as a potential noninvasive predictive biomarker of NAFLD, whose surrogate value increased when combined with other routine biochemical measurements (glucose/ALT).
... Anthropometric measurements (body weight, height and waist circumference), body composition (DXA, Lunar iDXA, encore 14.5, Madison, WI, USA), and blood pressure (Intelli Sense. M6, OMRON Healthcare, Hoofddorp, The Netherlands) were determined in fasting conditions under previously described standardized procedures [27]. The body mass index (BMI) was calculated as the body weight divided by the squared height (kg/m 2 ). ...
PurposeIdentification of dietary factors involved in the development and progression of nonalcoholic fatty liver disease (NAFLD) is relevant to the current epidemics of the disease. Dietary amino acids appear to play a key role in the onset and progression of NAFLD. The aim of this study was to analyze potential associations between specific dietary amino acids and variables related to glucose metabolism and hepatic status in adults with overweight/obesity and NAFLD.Methods
One hundred and twelve individuals from the Fatty Liver in Obesity (FLiO) study were evaluated. Liver assessment was carried out by ultrasonography, magnetic resonance imaging and analysis of biochemical parameters. Dietary amino acid intake (aromatic amino acids (AAA); branched-chain amino acids (BCAA); sulfur amino acids (SAA)) was estimated by means of a validated 137-item food frequency questionnaire.ResultsHigher consumption of these amino acids was associated with worse hepatic health. Multiple adjusted regression models confirmed that dietary AAA, BCAA and SAA were positively associated with liver fat content. AAA and BCAA were positively associated with liver iron concentration. Regarding ferritin levels, a positive association was found with BCAA. Dietary intake of these amino acids was positively correlated with glucose metabolism (glycated hemoglobin, triglyceride and glucose index) although the significance disappeared when potential confounders were included in the model.Conclusion
These findings suggest that the consumption of specific dietary amino acids might negatively impact on liver status and, to a lesser extent on glucose metabolism in subjects with overweight/obesity and NAFLD. A control of specific dietary amino acid composition should be considered in the management of NAFLD and associated insulin resistance. NCT03183193; June 2017.
... The BMI was calculated as body weight divided by squared height (kg/m 2 ). The body composition was analyzed by dual-energy X-ray absorptiometry (DXA) according to the instructions of the manufacturer (Lunar iDXA, encore 14.5, Madison, WI, USA) [27]. ...
Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver disease worldwide. Some genetic variants might be involved in the progression of this disease. The study hypothesized that individuals with the rs7359397 T allele have a higher risk of developing severe stages of NAFLD compared with non-carriers where dietary intake according to genotypes could have a key role on the pathogenesis of the disease. SH2B1 genetic variant was genotyped in 110 overweight/obese subjects with NAFLD. Imaging techniques, lipidomic analysis and blood liver biomarkers were performed. Body composition, general biochemical and dietary variables were also determined. The SH2B1 risk genotype was associated with higher HOMA-IR p = 0.001; and Fatty Liver Index (FLI) p = 0.032. Higher protein consumption (p = 0.028), less mono-unsaturated fatty acid and fiber intake (p = 0.045 and p = 0.049, respectively), was also referred to in risk allele genotype. Lipidomic analysis showed that T allele carriers presented a higher frequency of non-alcoholic steatohepatitis (NASH) (69.1% vs. 44.4%; p = 0.006). In the genotype risk group, adjusted logistic regression models indicated a higher risk of developing an advanced stage of NAFLD measured by FLI (OR 2.91) and ultrasonography (OR 4.15). Multinomial logistic regression models showed that risk allele carriers had higher liver fat accumulation risk (RRR 3.93) and an increased risk of NASH (RRR 7.88). Consequently, subjects carrying the T allele were associated with a higher risk of developing a severe stage of NAFLD. These results support the importance of considering genetic predisposition in combination with a healthy dietary pattern in the personalized evaluation and management of NAFLD.
... The macronutrient distribution of 50 % total caloric value (TCV) was from carbohydrates, 30% from lipids, 20% from proteins and a healthy fatty acids 30%. Subjects consumption of cholesterol was less than 300 mg/day and focused on low glycemic index and glycemic load (GL) carbohydrate meals [11,12]. ...
Background
Polycystic ovary syndrome (PCOS) is a common reproductive endocrine co-morbidity of obesity. Ghrelin is a peptide which regulates food intake and body weight. The aim of this study was to measure ghrelin levels in obesity and PCOS and to evaluate the impact of weight loss on plasma ghrelin level, metabolic, and phenotypic features of PCOS. This prospective comparative study enrolled obese women without PCOS ( N = 60) and obese PCOS women ( n = 50) and 85 control groups. Body compositions including fat mass (FM) and fat-free mass (FFM) were measured by dual-energy X-ray absorptiometry (DEXA). Plasma ghrelin concentrations were measured using enzyme-linked immunosorbent assay (ELISA).
Results
Our results revealed that plasma ghrelin levels were lower in PCOS patients compared to obese (9.49 ± 5.59 ng/ml) and controls (48.21 ± 21.09 ng/ml). Moreover, it was negatively correlated to anthropometric measures, glycemic, lipid profile, and the phenotype characteristics of PCOS. Interestingly, after 12 weeks of following the Mediterranean diet (MD)-based weight loss program, ghrelin levels were increased in both obese groups.
Conclusion
Successful weight loss leads to increase ghrelin levels in both obese and PCOS groups.
... This study was performed in 523 adult participants from cohorts composing the Methyl Epigenome Network Association (MENA) project such as DiOGenes-UNAV with n = 58 [17], OBEPALIP with n = 29 [18], Food4Me-UNAV with n = 42 [19], GEDYMET with n = 57 [20], ICTUS with n = 7 [21], NUGENOB-UNAV with n = 42 [22], PREDIMED-UNAV with n = 129 [23], RESMENA with n = 47 [24], OBEKIT with n = 100 [25], and NormoP with n = 12 [26], whose providers are gratefully acknowledged. Study design, characteristics, and exclusion and inclusion criteria of each of these cohorts have been previously described. ...
Epigenetic signatures such as DNA methylation may be associated with specific obesity traits in different tissues. The onset and development of some obesity-related complications are often linked to visceral fat accumulation. The aim of this study was to explore DNA methylation levels in peripheral white blood cells to identify epigenetic methylation marks associated with waist circumference (WC). DNA methylation levels were assessed using Infinium Human Methylation 450K and MethylationEPIC beadchip (Illumina) to search for putative associations with WC values of 473 participants from the Methyl Epigenome Network Association (MENA) project. Statistical analysis and Ingenuity Pathway Analysis (IPA) were employed for assessing the relationship between methylation and WC. A total of 669 CpGs were statistically associated with WC (FDR < 0.05, slope ≥ |0.1|). From these CpGs, 375 CpGs evidenced a differential methylation pattern between females with WC ≤ 88 and > 88 cm, and 95 CpGs between males with WC ≤ 102 and > 102 cm. These differentially methylated CpGs are located in genes related to inflammation and obesity according to IPA. Receiver operating characteristic (ROC) curves of the top four significant differentially methylated CpGs separated by sex discriminated individuals with presence or absence of abdominal fat. ROC curves of all the CpGs from females and one CpG from males were validated in an independent sample (n = 161). These methylation results add further insights about the relationships between obesity, adiposity-associated comorbidities, and DNA methylation where inflammation processes may be involved.
... Another factor that could have an important role is the macronutrient composition of the weight-loss diet. Both diets remained within the recommendations for adults proposed by the U.S. Institute of Medicine, and our previous studies [37][38][39]. Nowadays, there is consistent epidemiological evidence about an inverse relationship between a healthy dietary pattern, characterized by a high intake of fruits, vegetables, whole-grains, olive oil, fish, and a lower risk of depression [40,41]. On the other hand, unhealthy diets have been proven to be associated with depression and anxiety [42]. ...
Current evidence proposes diet quality as a modifiable risk factor for mental or emotional impairments. However, additional studies are required to investigate the effect of dietary patterns and weight loss on improving psychological symptoms. The aim of this investigation was to evaluate the effect of energy-restriction, prescribed to overweight and obese participants, on anxiety and depression symptoms, as well as the potential predictive value of some baseline psychological features on weight loss. Overweight and obese participants (n = 305) were randomly assigned for 16 weeks to two hypocaloric diets with different macronutrient distribution: a moderately high-protein (MHP) diet and a low-fat (LF) diet. Anthropometrical, clinical, psychological, and lifestyle characteristics were assessed at baseline and at the end of the intervention. The nutritional intervention evidenced that weight loss has a beneficial effect on trait anxiety score in women (β = 0.24, p = 0.03), depression score in all population (β = 0.15, p = 0.02), particularly in women (β = 0.22, p = 0.03) and in subjects who followed the LF diet (β = 0.22, p = 0.04). Moreover, weight loss could be predicted by anxiety status at baseline, mainly in women and in those who were prescribed a LF diet. This trial suggests that weight loss triggers an improvement in psychological traits, and that anxiety symptoms could predict those volunteers that benefit most from a balanced calorie-restricted intervention, which will contribute to individualized precision nutrition.
... A nutriepigenomic analysis was conducted in an adult population from the Methyl Epigenome Network Association (MENA) project (n = 474), which is constituted by previous clinical trials [27][28][29][30][31][32][33][34]. The study protocol, data confidentiality, and research procedures were in accordance with the ethical principles on human experimentation stipulated in the 2013 Declaration of Helsinki by the World Medical Association [35]. ...
Background
Olfaction is an important sense influencing food preferences, appetite, and eating behaviors. This hypothesis-driven study aimed to assess associations between olfactory pathway gene methylation signatures, obesity features, and dietary intakes.
Methods
A nutriepigenomic analysis was conducted in 474 adults from the Methyl Epigenome Network Association (MENA) project. Anthropometric measurements, clinical data, and serum metabolic profiles of the study population were obtained from structured databases of the MENA cohorts. Habitual dietary intake was assessed using a validated semiquantitative food frequency questionnaire. DNA methylation was measured in circulating white blood cells by microarray (Infinium Human Methylation 450 K BeadChips). FDR values (p < 0.0001) were used to select those CpGs that showed the best correlation with body mass index (BMI) and waist circumference (WC). Pathway analyses involving the characterization of genes involved in the olfactory transduction system were performed using KEGG and pathDIP reference databases.
Results
Overall, 15 CpG sites at olfactory pathway genes were associated with BMI (p < 0.0001) and WC (p < 0.0001) after adjustments for potential confounding factors. Together, methylation levels at the15 CpG sites accounted for 22% and 20% of the variability in BMI and WC (r² = 0.219, p < 0.001, and r² = 0.204, p < 0.001, respectively). These genes encompassed olfactory receptors (OR4D2, OR51A7, OR2T34, and OR2Y1) and several downstream signaling molecules (SLC8A1, ANO2, PDE2A, CALML3, GNG7, CALML6, PRKG1, and CAMK2D), which significantly regulated odor detection and signal transduction processes within the complete olfactory cascade, as revealed by pathway enrichment analyses (p = 1.94 × 10–10). Moreover, OR4D2 and OR2Y1 gene methylation patterns strongly correlated with daily intakes of total energy (p < 0.0001), carbohydrates (p < 0.0001), protein (p < 0.0001), and fat (p < 0.0001).
Conclusions
The results of this study suggest novel relationships between olfactory pathway gene methylation signatures, obesity indices, and dietary intakes.
... Anthropometric measurements such us body weight and waist circumference (WC), were determined in fasting conditions following previously described standardized procedures (12). Body composition was assessed by dual-energy x-ray absorptiometry (Lunar Prodigy, software version 6.0, Madison, WI) at baseline in accordance with validated protocols (13). Body mass Index (BMI) was calculated as body weight divided by height squared (kg/m 2 ) following accepted cut-off criteria (11). ...
Introduction: Non-alcoholic fatty liver disease (NAFLD) may progress to steatohepatitis, cirrhosis and complicated hepatocellular carcinoma with defined differential symptoms and manifestations.
Objective: To evaluate the fatty liver status by several validated approaches and to compare imaging techniques, lipidomic and routine blood markers with magnetic resonance imaging in adults subjects with non-alcoholic fatty liver disease.
Materials and methods: A total of 127 overweight/obese with NAFLD, were parallelly assessed by Magnetic Resonance Imaging (MRI), ultrasonography, transient elastography and a validated metabolomic designed test to diagnose NAFLD in this cross-sectional study. Body composition (DXA), hepatic related biochemical measurements as well as the Fatty Liver Index (FLI) were evaluated. This study was registered as FLiO: Fatty Liver in Obesity study; NCT03183193.
Results: The subjects with more severe liver disease were found to have worse metabolic parameters. Positive associations between MRI with inflammatory and insulin biomarkers were found. A linear regression model including ALT, RBP4 and HOMA-IR was able to explain 40.9% of the variability in fat content by MRI. In ROC analyses a combination panel formed of ALT, HOMA-IR and RBP4 followed by ultrasonography, ALT and metabolomic test showed the major predictive ability (77.3%, 74.6%, 74.3% and 71.1%, respectively) for liver fat content.
Conclusions: A panel combination including routine blood markers linked to insulin resistance showed highest associations with MRI considered as a gold standard for determining liver fat content. This combination of tests can facilitate the diagnosis of early stages of non-alcoholic liver disease thereby avoiding other invasive and expensive methods.
... Anthropometric measurements (body weight, waist circumference) were determined in fasting conditions following previously described standardized procedures [34]. The BMI was calculated as body weight divided by squared height (kg/m 2 ). ...
Background: Dietary total antioxidant capacity (TAC), glycemic index (GI), and glycemic load (GL) are accepted indicators of diet quality, which have an effect on diet–disease relationships. The aim of this study was to evaluate potential associations of dietary TAC, GI, and GL with variables related to nutritive status and insulin resistance (IR) risk in cardiometabolic subjects. Methods: A total of 112 overweight or obese adults (age: 50.8 ± 9 years old) were included in the trial. Dietary intake was assessed by a validated 137-item food frequency questionnaire (FFQ), which was also used to calculate the dietary TAC, GI, and GL. Anthropometrics, blood pressure, body composition by dual-energy X-ray absorptiometry (DXA), glycemic and lipid profiles, C-reactive protein (CRP), as well as fatty liver quantification by magnetic resonance imaging (MRI) were assessed. Results: Subjects with higher values of TAC had significantly lower circulating insulin concentration and homeostatic model assessment of insulin resistance (HOMA-IR). Participants with higher values of HOMA-IR showed significantly higher GI and GL. Correlation analyses showed relevant inverse associations of GI and GL with TAC. A regression model evidenced a relationship of HOMA-IR with TAC, GI, and GL. Conclusion: This data reinforces the concept that dietary TAC, GI, and GL are potential markers of diet quality, which have an impact on the susceptible population with a cardiometabolic risk profile.
... A general population of 474 adults within the Methyl Epigenome Network Association (MENA) project was included, which is constituted from previous clinical trials evaluating relationships between diet, obesity, and related comorbidities, as well as genetic profiles (18)(19)(20)(21)(22)(23)(24)(25). All these studies have received ethical approval to perform such analyses. ...
Obesity and type 2 diabetes mellitus are independent risk factors for the onset and progression of hepatocellular carcinoma (HCC). This study aimed to analyze the association of DNA methylation signatures at HCC pathway genes with obesity and related metabolic disturbances. A population of 474 adults within the Methyl Epigenome Network Association (MENA) project was included. DNA methylation levels were measured in white blood cells by microarray. The identification and discrimination of HCC pathway genes were performed using KEGG and PathDIP databases. Anthropometry measurements, the blood metabolic profile, and clinical data were analyzed. The methylation patterns of 20 CpG sites at HCC pathway genes strongly correlated with BMI (FDR <0.0001). These genes encompassed GADD45A, MTOR, FRAT2, E2F3, WNT7B, FRAT1, LRP5, DPF3, GSTA2, APC, MYC, WNT10B, ARID1B, AKT1, GSTA1, WNT5A, CDK4, GAB1, TCF7, which statistically contributed to the regulation of the HCC pathway (P = 2.10e-07). The main biological process where these genes were implicated included uncontrolled cell proliferation, DNA damage, increased survival, and altered oncogenic expression. Interestingly, 9 out of 20 BMI-associated CpGs also correlated with waist circumference and HOMA-IR index. In conclusion, pathway analysis revealed potential associations of DNA methylation signatures at HCC pathway genes with adiposity and insulin resistance phenotypes.
... The current study was conducted in a subsample of the RESMENA (Metabolic Syndrome Reduction in Navarra) nutritional intervention trial. In this study, 96 adults with metabolic syndrome underwent two energy-restricted dietary patterns (AHA diet as reference diet, and RESMENA diet as intervention diet) during 8 weeks, both with an energy restriction of -30% of the studied requirements [12]. As no differences were found neither in anthropometric or biochemical variables between groups after the intervention, both dietary groups were merged for further analyses to increase the statistical power of the study, classifying subjects in "high-responders" (HR) when weight loss was !8%, and "low responders" (LR) when weight loss was 8%, as previously published [4]. ...
Background
Non-coding RNAs (i.e., miRNAs) play a role in the development of obesity and related comorbidities and the regulation of body weight.
Objective
To identify candidate miRNA biomarkers throughout omics approaches in order to predict the response to specific weight-loss dietary treatments.
Design
Genomic DNA and cDNA isolated from white blood cells of a subset from the RESMENA nutritional intervention study (Low-responders (LR) vs High-responders (HR)) was hybridized in Infinium Human Methylation450 BeadChip and in Illumina Human HT-12 v4 gene expression BeadChips arrays respectively. A bioinformatic prediction of putative target sites of selected miRNAs was performed by applying miRBase algorithms. HEK-293T cells were co-transfected with expression vectors containing the 3’-UTR of candidate genes to validate the binding of miRNAs to its target sites.
Results
134 miRNAs were differentially methylated between HR and LR in the methylation array, whereas 44 miRNAs were differentially expressed between both groups in the expression array. Specifically, miR-1237, miR-1976, miR-642, miR-636, miR-612 and miR-193B were simultaneously hypomethylated and overexpressed in HR. miR-612 and miR-1976 showed greatest differences in methylation and expression levels, respectively. The bioinformatic prediction revealed that TP53 was a putative target gene of miR-612 and CD40 of miR-1976. Moreover, TP53 was downregulated in the expression array when comparing HR vs LR expression levels adjusted by sex, diet, age and baseline weight, and CD40 showed a statistical trend. Furthermore, gene expression levels of TP53 and CD40 in white blood cells, when measured by qPCR, were also downregulated in HR. Finally, miR-612 and miR-1976 potently repressed TP53 and CD40 respectively by targeting its 3’-UTR regions.
Conclusion
miR-612 and miR-1976 levels could be prospective biomarkers of response to specific weight-loss diets and might regulate the gene expression of TP53 and CD40.
... In another trial carried out with patients presenting features of the metabolic syndrome, within the RESMENA study ( Zulet et al. 2011;de la Iglesia et al. 2014), it was observed that protein quality may have an important impact in overweight/obesity, but also in related diseases ( Lopez-Legarrea et al. 2014). In this context, consuming vegetable protein sources under energy restriction was specifically associated to a reduction of inflammatory markers, which allowed to hypothesise that obesity could also be tackled through this anti-inflammatory process. ...
The objective was to evaluate differences in macronutrient intake and to investigate the possible association between consumption of vegetable protein and the risk of overweight/obesity, within the Food4Me randomised, online intervention. Differences in macronutrient consumption among the participating countries grouped by EU Regions (Western Europe, British Isles, Eastern Europe and Southern Europe) were assessed. Relation of protein intake, within isoenergetic exchange patterns, from vegetable or animal sources with risk of overweight/obesity was assessed through the multivariate nutrient density model and a multivariate-adjusted logistic regression. A total of 2413 subjects who completed the Food4Me screening were included, with self-reported data on age, weight, height, physical activity and dietary intake. As success rates on reducing overweight/obesity are very low, form a public health perspective, the elaboration of policies for increasing intakes of vegetable protein and reducing animal protein and sugars, may be a method of combating overweight/obesity at a population level.
... Anthropometric measurements, such as body weight and waist circumference (WC), were determined in fasting conditions following previously described standardized procedures [20]. Visceral Adipose Tissue (VAT) and body composition were assessed by dual-energy x-ray absorptiometry (Lunar Prodigy, software version 6.0, Madison, WI) at baseline and after 6 months with the subjects in their underwear in accordance with validated protocols [21]. BMI was calculated as body weight divided by squared height (kg/m 2 ). ...
Background:
Obesity and comorbidities such as non-alcoholic fatty liver disease (NAFLD) are major public health burdens. Alterations in lipid metabolism are involved in hepatic diseases. The objective of this study was to assess the influence of weight loss on lysophospholipid (LP) metabolism and liver status in obese subjects as well as to provide new evidence regarding the interaction of LP metabolism as a key factor in the onset and management of obesity-related diseases such as liver damage.
Methods:
Thirty-three subjects from the RESMENA (Reduction of Metabolic Syndrome in Navarra, NCT01087086) study were selected based on their Fatty Liver Index (FLI). Plasma lipid species (lysophosphatidilcholine: LPC, lysophosphatidilethanolamines: LPE and lysophosphatidylinositols: LPI specifically) were determined by LC-MS, while waist circumference (WC) and other non-invasive liver markers such as, FLI and BAAT scores as well as dietary records, anthropometrical measurements, body composition by DXA and other metabolic determinants were analyzed before and after a six-month hypocaloric nutritional intervention.
Results:
Computed Z-scores of total LP (LPC, LPE, and LPI) were significantly decreased after 6-months of following a hypocaloric diet. Specifically, LPC14:0, LPC15:0, LPC16:1, LPC18:4, LPC20:4, showed clear relationships with weight loss. Changes in FLI score, WC and BAAT score revealed associations with general changes in LPC score. Interestingly the BAAT score was statistically associated with the LPC score after adjustment for weight loss.
Conclusion:
The lipidomic LPC profile analysis revealed a generalized decrease in circulating lysophospholipids after weight loss. The involvement of particular LP in liver metabolism and obesity merit further attention, as some of these specific non-invasive liver markers were reduced independently of weight loss.
Trial registration:
NCT01087086. Registered 15 March 2010, retrospectively registry.
... A transversal nutriepigenomic analysis was conducted in a general adult population within the Methyl Epigenome Network Association (MENA) project (n = 473). The MENA cohort is constituted by pre- vious clinical trials analyzing genome-environmental interactions concerning weight management and associated metabolic outcomes ( Abete et al., 2015;Huerta, Navas-Carretero, Prieto-Hontoria, Martínez, & Moreno-Aliaga, 2015;Larsen et al., 2010;MartínezGonzález et al., 2014;Petersen et al., 2006;San-Cristobal et al., 2015;Santos et al., 2016;Zulet et al., 2011). Each study received ethical approval from appropriate local Human Research Ethics ...
Introduction
Dopamine (DA) is a neurotransmitter that regulates the rewarding and motivational processes underlying food intake and eating behaviors. This study hypothesized associations of DNA methylation signatures at genes modulating DA signaling with obesity features, metabolic profiles, and dietary intake.
Methods
An adult population within the Methyl Epigenome Network Association project was included (n = 473). DNA methylation levels in white blood cells were measured by microarray (450K). Differentially methylated genes were mapped within the dopaminergic synapse pathway using the KEGG reference database (map04728). Subsequently, network enrichment analyses were run in the pathDIP portal. Associations of methylation patterns with anthropometric markers of general (BMI) and abdominal obesity (waist circumference), the blood metabolic profile, and daily dietary intakes were screened.
Results
After applying a correction for multiple comparisons, 12 CpG sites were strongly associated (p < 0.0001) with BMI: cg03489495 (ITPR3), cg22851378 (PPP2R2D), cg04021127 (PPP2R2D), cg22441882 (SLC18A1), cg03045635 (DRD5), cg23341970 (ITPR2), cg13051970 (DDC), cg08943004 (SLC6A3), cg20557710 (CACNA1C), cg24085522 (GNAL), cg16846691 (ITPR2), and cg09691393 (SLC6A3). Moreover, average methylation levels of these genes differed according to the presence or absence of abdominal obesity. Pathway analyses revealed a statistically significant contribution of the aforementioned genes to dopaminergic synapse transmission (p = 4.78E−08). Furthermore, SLC18A1 and SLC6A3 gene methylation signatures correlated with total energy (p < 0.001) and carbohydrate (p < 0.001) intakes.
Conclusions
The results of this investigation reveal that methylation status on DA signaling genes may underlie epigenetic mechanisms contributing to carbohydrate and calorie consumption and fat deposition.
... A population of 474 adults belonging to the Methyl Epigenome Network Association (MENA) project was included. The MENA cohort is constituted from eight previous clinical trials (Larsen et al. 2010;Zulet et al. 2011;Petersen et al. 2006;San-Cristobal et al. 2015;Martínez-González et al. 2014;Huerta et al. 2015;Santos et al. 2016;Abete et al. 2015). The study variables analyzed in this investigation were obtained at baseline from structured databases of the different MENA project cohorts. ...
The circadian clock regulates the daily rhythms of several physiological and behavioral processes. Disruptions in clock genes have been associated with obesity and related comorbidities. This study aimed to analyze the association of DNA methylation signatures at circadian rhythm pathway genes with body mass index (BMI), metabolic profiles and dietary intakes. DNA methylation profiling was determined by microarray in white blood cells from 474 adults from the Methyl Epigenome Network Association (MENA) project. Kyoto Encyclopedia of Genes and Genomes database was used to identify the genes integrating the circadian rhythm pathway. Network enrichment analyses were performed with the PathDIP platform. Associations between circadian methylation patterns with anthropometric measurements, the metabolic profile, clinical data and dietary intakes were analyzed. DNA methylation patterns of nine CpG sites at six circadian rhythm pathway genes were strongly correlated with BMI (false discovery rates <0.0001). These CpGs encompassed cg09578018 (RORA), cg20406576 (PRKAG2), cg10059324 (PER3), cg01180628 (BHLHE40), cg23871860 (FBXL3), cg16964728 (RORA), cg14129040 (CREB1), cg07012178 (PRKAG2) and cg24061580 (PRKAG2). Interestingly, network enrichment analyses revealed that the six BMI-associated genes statistically contributed to the regulation of the circadian rhythm pathway (p = 1.9E-10). In addition, methylation signatures at cg09578018 (RORA), cg24061580 (PRKAG2), cg01180628 (BHLHE40) and cg10059324 (PER3) also correlated with insulin resistance (p < 0.0001) and mean arterial blood pressure (p < 0.0001). Furthermore, relevant correlations (p < 0.05) between methylation at cg09578018 (RORA) and cg01180628 (BHLHE40) with total energy and carbohydrate intakes were found. This investigation revealed potential associations of DNA methylation profiles at circadian genes with obesity, metabolic disturbances and carbohydrate intake, with potential impact on weight homeostasis.
... An epigenomic analysis within the Methyl Epigenome Network Association (MENA) project was conducted involving 474 adults from previous study cohorts [16][17][18][19][20][21][22][23]. All procedures of this study were in accordance with the ethical principles of the Helsinki Declaration including the codification of the subject's data in order to guarantee anonymity and appropriate ethical requirements to carry out the research. ...
A sustained activation of the unfolded protein response and the subsequent endoplasmic reticulum (ER) stress has been involved in the onset and severity of several metabolic diseases. The aim of this study was to analyze the association of DNA methylation signatures at ER stress genes with adiposity traits and related metabolic disorders. An epigenomic analysis within the Methyl Epigenome Network Association (MENA) project was conducted in an adult population (n=474). DNA methylation status in peripheral white blood cells was analyzed by a microarray approach. KEGG database was used to the characterization and discrimination of genes involved in the "protein processing in endoplasmic reticulum pathway". Anthropometric measurements and plasma metabolic profiles were analyzed. A total of 15 CpG sites at genes participating in ER pathway were strongly correlated with BMI after adjusted linear regression analyses (p<0.0001). These included cg08188400 (MAP2K7), cg20541779 (CASP12), cg24776411 (EIF2AK1), cg14190817 (HSPA5), cg21376454 (ERN1), cg06666486 (EIF2AK1), cg03211481 (DNAJC1), cg18357645 (OS9), cg05801879 (MBTPS1), cg20964082 (ERO1LB), cg17300868 (NFE2L2), cg03384128 (EIF2AK4), cg02712587 (EIF2AK4), cg04972384 (SELS), cg02240686 (EIF2AK2). Noteworthy, most of them were implicated in ER stress (p=2.9E-09). However, only methylation levels at cg20964082 (ERO1LB), cg17300868 (NFE2L2), cg05801879 (MBTPS1), and cg03384128 (EIF2AK4) also correlated with total fat mass. Interestingly, significant associations between methylation patterns at cg20964082 (ERO1LB) and cg17300868 (NFE2L2) and insulin and HOMA-IR index were found, whereas cg05801879 (MBTPS1) and cg03384128 (EIF2AK4) were correlated with triglyceride levels. This study suggests associations of methylation signatures at ER stress genes with adiposity and insulin resistance, as revealed by discriminative pathway analyses.
... A nutriepigenomic analysis within the Methyl Epigenome Network Association (MENA) project was conducted in 474 adults from previous cohorts (Abete et al., 2015;Huerta, Navas-Carretero, Prieto-Hontoria, Martínez, & Moreno-Aliaga, 2015;Larsen et al., 2010;Martínez-Gonz alez et al., 2014;Petersen et al., 2006;San-Cristobal et al., 2015;Santos et al., 2016;Zulet et al., 2011) which constitutes the MENA project. The study protocol was in accordance with the ethical principles of the Helsinki Declaration. ...
Individual differences in taste perception may influence appetite, dietary intakes, and subsequently, disease risk. Correlations of DNA methylation patterns at taste transducing genes with BMI and dietary intakes were studied. A nutriepigenomic analysis within the Methyl Epigenome Network Association (MENA) project was conducted in 474 adults. DNA methylation in peripheral white blood cells was analyzed by a microarray approach. KEGG pathway analyses were performed concerning the characterization and discrimination of genes involved in the taste transduction pathway. Adjusted FDR values (p < 0.0001) were used to select those CpGs that showed best correlation with BMI. A total of 29 CpGs at taste transducing genes met the FDR criteria. However, only 12 CpGs remained statistically significant after linear regression analyses adjusted for age and sex. These included cg15743657 (TAS1R2), cg02743674 (TRPM5), cg01790523 (SCN9A), cg15947487 (CALHM1), cg11658986 (ADCY6), cg04149773 (ADCY6), cg02841941 (P2RY1), cg02315111 (P2RX2), cg08273233 (HTR1E), cg14523238 (GABBR2), cg12315353 (GABBR1) and cg05579652 (CACNA1C). Interestingly, most of them were implicated in the sweet taste signaling pathway, except CACNA1C (sour taste). In addition, TAS1R2 methylation at cg15743657 was strongly correlated with total energy (p < 0.0001) and carbohydrate intakes (p < 0.0001). This study suggests that methylation in genes related to sweet taste could be an epigenetic mechanism associated with obesity.
... Rather than measuring longevity directly, CR studies in humans typically measure biomarkers correlated with longevity, including those indicated above for animals. CR plans are typically implemented for a period of 6-12 months [68][69][70][71][72][73][74][75][76][77][78][79][80]but some studies have extended the timeframe beyond this point [26,[81][82][83][84] . The majority of published work has included healthy, middle aged, men and women with normal body mass. ...
Although weight loss is often the impetus for beginning a dietary program, multiple physiological benefits are typically observed when someone embarks on a dietary regimen involving reduced caloric intake. Many of these changes, such as a reduction in blood pressure, an improvement in blood lipids and insulin sensitivity, and a reduction in inflammation and oxidative stress, can be viewed as favorable in terms of cardio-metabolic health. The positive changes are not only realized if individuals follow a hypo-caloric diet. In fact, simply altering the timing of the overall caloric intake over the period of the day or week can result in profound benefits. Alternatively, manipulating the macronutrient composition of the diet can be met with favorable outcomes,
in particular when the dietary plan includes high quantities of nutrient dense, fiber-rich foods. This brief review discusses four different dietary approaches that have been shown to be effective alternatives to the traditional dietary plans most commonly followed. The plans discussed include caloric restriction, alternate day fasting, intermittent fasting, and dietary restriction. Findings from both animal and human studies are discussed, as appropriate.
... In particular, genetic polymorphisms in relevant genes have been related with each one of the traditional biomarkers previously mentioned. In addition, the underlying mechanisms by which the MedDiet exercises its beneficial effects on CVD are not well known (Table 1) [42][43][44][45][46][47][48]. It is thought that omics integration in the studies analyzing nutrition and CVD will provide new clues regarding these mechanisms [49]. ...
Intervention with Mediterranean diet (MedDiet) has provided a high level of evidence in primary prevention of cardiovascular events. Besides enhancing protection from classical risk factors, an improvement has also been described in a number of non-classical ones. Benefits have been reported on biomarkers of oxidation, inflammation, cellular adhesion, adipokine production, and pro-thrombotic state. Although the benefits of the MedDiet have been attributed to its richness in antioxidants, the mechanisms by which it exercises its beneficial effects are not well known. It is thought that the integration of omics including genomics, transcriptomics, epigenomics, and metabolomics, into studies analyzing nutrition and cardiovascular diseases will provide new clues regarding these mechanisms. However, omics integration is still in its infancy. Currently, some single-omics analyses have provided valuable data, mostly in the field of genomics. Thus, several gene-diet interactions in determining both intermediate (plasma lipids, etc.) and final cardiovascular phenotypes (stroke, myocardial infarction, etc.) have been reported. However, few studies have analyzed changes in gene expression and, moreover very few have focused on epigenomic or metabolomic biomarkers related to the MedDiet. Nevertheless, these preliminary results can help to better understand the inter-individual differences in cardiovascular risk and dietary response for further applications in personalized nutrition.
... Hence, metabolomics can answer questions such as how a high-saturated fat diet can affect lipid profile, or how the intake of fiber affects glycemia. Recent dietary intervention studies using metabolic profiles have evaluated the consequences of consuming cocoa [96] , coffee [97] and fiber [98] , and of different dietary patterns [99] . Study of metabolites is only possible with advances in techniques that separate and identify small molecules [100] . ...
Diversity in the genetic profile between individuals and specific ethnic groups affects nutrient requirements, metabolism and response to nutritional and dietary interventions. Indeed, individuals respond differently to lifestyle interventions (diet, physical activity, smoking, etc.). The sequencing of the human genome and subsequent increased knowledge regarding human genetic variation is contributing to the emergence of personalized nutrition. These advances in genetic science are raising numerous questions regarding the mode that precision nutrition can contribute solutions to emerging problems in public health, by reducing the risk and prevalence of nutrition-related diseases. Current views on personalized nutrition encompass omics technologies (nutrigenomics, transcriptomics, epigenomics, foodomics, metabolomics, metagenomics, etc.), functional food development and challenges related to legal and ethical aspects, application in clinical practice, and population scope, in terms of guidelines and epidemiological factors. In this context, precision nutrition can be considered as occurring at three levels: (1) conventional nutrition based on general guidelines for population groups by age, gender and social determinants; (2) individualized nutrition that adds phenotypic information about the person's current nutritional status (e.g. anthropometry, biochemical and metabolic analysis, physical activity, among others), and (3) genotype-directed nutrition based on rare or common gene variation. Research and appropriate translation into medical practice and dietary recommendations must be based on a solid foundation of knowledge derived from studies on nutrigenetics and nutrigenomics. A scientific society, such as the International Society of Nutrigenetics/Nutrigenomics (ISNN), internationally devoted to the study of nutrigenetics/nutrigenomics, can indeed serve the commendable roles of (1) promoting science and favoring scientific communication and (2) permanently working as a 'clearing house' to prevent disqualifying logical jumps, correct or stop unwarranted claims, and prevent the creation of unwarranted expectations in patients and in the general public. In this statement, we are focusing on the scientific aspects of disciplines covering nutrigenetics and nutrigenomics issues. Genetic screening and the ethical, legal, social and economic aspects will be dealt with in subsequent statements of the Society.
Several clinical studies have attributed the Mediterranean diet (MedDiet) to desirable metabolic health outcomes, but literature is saturated with studies conducted in Mediterranean regions questioning the diets applicability in non-Mediterranean countries. This review aimed to determine the effectiveness of MedDiet compared to a low-fat diet (LF-Diet) on metabolic components in those with or at risk of developing Metabolic Syndrome (MetS) in non-Mediterranean countries. We searched Medline, Embase and Global Health for randomized controlled trials published until October 2022 and a clinical trial register for ongoing studies. We identified 13 published trials (n = 1921) and 2 ongoing trials that met inclusion criteria. Random effects meta-analysis, yielded a statistically significant reduction in total cholesterol (MD -7.97, 95%CI -14.82 to −1.11) and systolic blood pressure (MD -2.04 mg/dl, 95%CI -3.68 to −0.39). Small non-significant pooled mean difference (MD) was observed for seven other MetS risk factors (body weight, waist circumference, diastolic blood pressure, blood glucose, triglycerides, LDL and HDL-cholesterol). Further inquiry is required to enhance certainty in estimates before health care providers can make an informed decision about possible dietary changes in MetS management and comorbidity prevention.
Obesity is a complex, multifactorial, lifestyle-related disorder which affects nearly one-third of the global population. In more than one way, obesity classifies as a potential indicator or contributing factor of various clinical conditions, subsequently leading to poor health outcomes and compromised quality of life (QoL). The high prevalence and reporting rate of obesity is irrespective of geographical difference, ethnicity and gender, however, they most often serve as predisposing risk factors for obesity. Additionally, environmental changes, availability & affordability of low nutrition, yet palatable food, hormonal disbalance and variation at the genetic level, prominently exacerbates the condition of obesity and its related effects. Clinically, obesity, may either lead to other pathophysiological conditions as well, such as liver dysfunction, polycystic ovarian syndrome, hypertension, coronary artery diseases and psychological impairment or vice-versa. Henceforth, to cope with the challenges of obesity and related conditions, a healthy lifestyle, personal care & social well-being is of prime importance. Additionally, a customized strategy to address the economic expenditure and newer therapeutic perspectives should be implemented to control the widespread damage of human population by this condition. The present review focuses on providing a brief knowledge about nutritional, biochemical, genetic and psychological aspects of obesity and its epidemiology.
The distribution of adipose tissue is influenced by gender and by age, shifting from subcutaneous to visceral depots with longevity, increasing the development of several aging-related diseases and manifestations such as obesity, metabolic syndrome, and insulin resistance. Epigenetics might have an important role in aging processes. The aim of this research was to investigate the interactions between aging and epigenetic processes and the role of visceral adipose tissue, insulin resistance, and dyslipidaemia. Two different study samples of 366 and 269 adult participants were analyzed. Anthropometric, biochemical (including the triglycerides-glucose (TyG) index), and blood pressure measurements were assessed following standardized methods. Body composition measurements by Dual-energy X-ray absorptiometry (DXA) were also performed for the second sample. Methylation data were assessed by Infinium Human Methylation BeadChip (Illumina) in peripheral white blood cells. Epigenetic age acceleration was calculated using the methods DNAmAge (AgeAcc) and GrimAge (AgeAccGrim). Age acceleration (AgeAccGrim) showed better correlations than AgeAcc with most of the measured variables (waist circumference, glucose, HOMA-IR, HDL-cholesterol, triglycerides, and TyG index) for the first sample. In the second sample, all the previous correlations were confirmed, except for HOMA-IR. In addition, many of the anthropometrical measurements assessed by DXA and C-reactive protein (CRP) were also statistically associated with AgeAccGrim. Associations separated by sex showed statistically significant correlations between AgeAccGrim and HDL-cholesterol or CRP in women, whereas, in men, the association was with visceral adipose tissue mass DXA, triglycerides and TyG index. Linear regression models (model 1 included visceral adipose tissue mass DXA and TyG index and model 2 included HDL-cholesterol and CRP) showed a significant association for men concerning visceral adipose tissue mass DXA and TyG index, while HDL-cholesterol and CRP were associated in women. Moreover, structural equation modeling showed that the TyG index was mediating the majority of the visceral adipose tissue mass action on age acceleration. Collectively, these findings showed that there are different mechanisms affecting epigenetic age acceleration depending on sex. The identified relationships between epigenetic age acceleration and disease markers will contribute to the understanding of the development of age-related diseases.
Background:
Obesity is a major contributor to preventable disease and death across the globe. Obesity is complex. Although its risk factors are myriad and compounding, there is an urgent need for a deeper understanding of the way risk factors interact with each other. Leptin is a peptide regulates food intake and body weight. However, the notion of leptin as an anti-obesity hormone was called into question because obesity is typically associated with high leptin levels and not leptin deficiency thus, we aimed to measure leptin levels in obese female in correlation to anthropometric measures and to evaluate the impact of weight loss on its level and metabolic parameters.
Subject and methods:
case-control study enrolled 40 control groups, 50 obese women. We measured anthropometric measures BMI, Waist/hip ratio (WHR). Fat mass index (FMI%) and free fat mass index (FFMI%) were assessed by dual energy X-Ray absorptiometry (DEXA) The serum levels of leptin were measured by ELISA.
Results:
Our results revealed that serum leptin levels were higher in obese women compared to controls. Moreover, it was positively correlated to anthropometric measures, glycemic and lipid profile. Linear regression analysis revealed that BMI was the main independent studied parameters associated with serum leptin level among other clinical and laboratory biomarkers. Interestingly, after 12 weeks of following the Mediterranean diet (MD)-based weight loss program, serum leptin levels were decreased. Logistic regression analysis was performed to detect the main predictors' biomarkers associated with weight loss among obese women. We found that serum leptin and FMI% were an independent predictor of response with odds ratios of 1.69 and 1.64 respectively (P < 0.001), Receiver operating characteristic analyses revealed that the AUC of serum leptin in discriminating obese women from lean ones was 0.893 (95% CI = 0.815-0.917) with sensitivity = 90%, specificity = 96%, and the cutoff values was 36.32 ng/ml.
Conclusion:
Serum leptin could be a valuable diagnostic marker of obesity and its comorbidities. Moreover, significant weight loss leads to decrease serum leptin levels and improvement of glycemic and lipid profiles.
Insulin resistance (IR) is a hallmark of type 2 diabetes, metabolic syndrome and cardiometabolic risk. An epigenetic phenomena such as DNA methylation might be involved in the onset and development of systemic IR. The aim of this study was to explore the genetic DNA methylation levels in peripheral white blood cells with the objective of identifying epigenetic signatures associated with IR measured by the Homeostatic Model Assessment of IR (HOMA-IR) following an epigenome-wide association study approach. DNA methylation levels were assessed using Infinium Methylation Assay (Illumina), and were associated with HOMA-IR values of participants from the Methyl Epigenome Network Association (MENA) project, finding statistical associations for at least 798 CpGs. A stringent statistical analysis revealed that 478 of them showed a differential methylation pattern between individuals with HOMA-IR ≤ 3 and > 3. ROC curves of top four CpGs out of 478 allowed differentiating individuals between both groups (AUC≈0.88). This study demonstrated the association between DNA methylation in some specific CpGs and HOMA-IR values that will help to the understanding and in the development of new strategies for personalized approaches to predict and prevent IR-associated diseases.
Purpose:
The interindividual variable response to weight-loss treatments requires the search for new predictive biomarkers for improving the success of weight-loss programs. The aim of this study is to identify novel genes that distinguish individual responses to a weight-loss dietary treatment by using the integrative analysis of mRNA expression and DNA methylation arrays.
Methods:
Subjects from Metabolic Syndrome Reduction in Navarra (RESMENA) project were classified as low (LR) or high (HR) responders depending on their weight loss. Transcriptomic (n = 24) and epigenomic (n = 47) patterns were determined by array-based genome-wide technologies in human white blood cells at the baseline of the treatment period. CD44 expression was validated by qRT-PCR and methylation degree of CpGs of the gene was validated by MassARRAY® EpiTYPER™ in a subsample of 47 subjects. CD44 protein levels were measured by ELISA in human plasma.
Results:
Different expression and DNA methylation profiles were identified in LR in comparison to HR. The integrative analysis of both array data identified four genes: CD44, ITPR1, MTSS1 and FBXW5 that were differently methylated and expressed between groups. CD44 showed higher expression and lower DNA methylation levels in LR than in HR. Although differences in CD44 protein levels between LR and HR were not statistically significant, a positive association was observed between CD44 mRNA expression and protein levels.
Conclusions:
In summary, the combination of a genome-wide methylation and expression array dataset can be a useful strategy to identify novel genes that might be considered as predictors of the dietary response. CD44 gene transcription and methylation may be a possible candidate biomarker for weight-loss prediction.
Body weight and fat content as well as enery metabolism depends on several factors such as food intake, nutrient-associated turnover, thermogenesis, and physical activity. These elements underlie complex interrelated feedback mechanisms, which are affected by personal genetic traits. A number of investigations have evidenced that not all calorie may count equal and that some specific biofactors occurring in foods may affect energy efficiency and fat deposition. Thus, the role of protein and specific amino acids, the glycemic load of different carbohydrates and foods, the type of fats, as well as the involvement of some food components with bioactive functions affecting the energy equation are being ascertained, since they can influence body composition and adiposity. Indeed, moderately high protein intake, carbohydrate with low glycemic index, n-3 fatty acids, calcium, and some thermogenic substances and antioxidants have been found to possibly contribute to reduce the body fat content. Many of these findings have been supported not only through epidemiological studies, but also by animal and cell investigations as well as through controlled nutritional interventions in humans. A better understanding of the putative involved mechanisms concerning the effects of individual fatty acids such as conjugated linoleic acid, eicosapentaenoic acid, and docosahexaenoic acid in body composition maintenance, as well as the identification of new bioactive compounds affecting lipid turnover and energy metabolism will open the way for a better control and management of fat deposition in different stages of the life cycle, since some of them are able to control relevant metabolic pathways at the molecular level, which will contribute to precision nutrition.
The impact of the normal whole diet in different countries and of special types of diet on the biomarkers of the metabolic syndrome (MetS) is reviewed. Diet type, specification, risk of MetS and studied biomarkers, as far as could be traced, are included. Critical points in published studies are mentioned. Description of the traditional dietary patterns for the various countries is not always well-defined and numbers of persons in the studied population are sometimes quite limited, which hamper drawing definite conclusions. Since a Nordic diet, a dietary approach to stop hypertension (DASH), and especially a Mediterranean diet are quite promising, due to its health claims, the food pattern is studied more in detail and a large spectrum of vegetarian diets are included as well. Most of the time lipid profile and high sensitive C-reactive protein (hsCRP) are the studied biomarkers in response to diet intake.
Through anepigenomics approach, the possible association between baseline levels in DNA methylation and a better weight loss response after a multidisciplinary intervention program were analyzedin obese population from RESMENA-S study. Three DNA regions that are differentially methylated (RGS6, A2BP1 and RASGRF1 genes) showed differential methylation levels at baseline between high and low responders to the multidisciplinary weight loss intervention. Moreover, these genes were implicated in the same metabolic pathway and have been previously significantly associated with obesity.
Purpose
– This paper aims to examine the effects of professional job experience on the lifestyle and dietary habits of participants who have studied food science and nutrition and acquired a dietitian license. The dietary habits of students of departments of food science and nutrition have been reported. However, no study has compared the dietary habits of graduates with and without actual clinical experience.
Design/methodology/approach
– In total, 206 participants who graduated from the department of food science and nutrition of a university located in Tokyo between 1975 and 1984 completed a questionnaire on food and nutrient intake and lifestyle habits in 2011.
Findings
– Total fat and SFA intake adjusted for energy intake or frequency of snack and fast food intake differed among participants with and without experience as dietitians, indicating that dietitian experience influenced the dietary habits of participants for approximately 30 years after graduation. Nutritional knowledge and skills acquired during attendance at a dietitian school are effective in maintaining favorable behavior for a long time. However, nutritional knowledge and skills were enhanced by later professional experience.
Originality/value
– The refining effect of clinical experience appears to contribute to the maintenance of daily dietary habits and health. Professional experience can contribute to the prevention of lifestyle-related diseases not only personally but also for other people in terms of public health nutrition or nutritional education.
The increase in the prevalence of obesity has coincided with an increase in portion sizes of foods both inside and outside the home, suggesting that larger portions may play a role in the obesity epidemic. Although it will be difficult to establish a causal relationship between increasing portion size and obesity, data indicate that portion size does influence energy intake. Several well-controlled, laboratory-based studies have shown that providing older children and adults with larger food portions can lead to significant increases in energy intake. This effect has been demonstrated for snacks and a variety of single meals and shown to persist over a 2-d period. Despite increases in intake, individuals presented with large portions generally do not report or respond to increased levels of fullness, suggesting that hunger and satiety signals are ignored or overridden. One strategy to address the effect of portion size is decreasing the energy density (kilojoules per gram; kilocalories per gram) of foods. Several studies have demonstrated that eating low-energy-dense foods (such as fruits, vegetables, and soups) maintains satiety while reducing energy intake. In a clinical trial, advising individuals to eat portions of low-energy-dense foods was a more successful weight loss strategy than fat reduction coupled with restriction of portion sizes. Eating satisfying portions of low-energy-dense foods can help to enhance satiety and control hunger while restricting energy intake for weight management.
BACKGROUND: Metabolic Syndrome (MS) is defined as a set of cardiovascular risk factors related to visceral obesity and insulin resistance that lead to an increase in general mortality, especially cardiovascular. The inflammatory markers are considered emergent risk factors and can be potentially used in the clinical stratification of cardiovascular diseases, establishing prognostic values. OBJECTIVE: This study aims at evaluating which components of the MS present an increase of IL-6 and hs-CRP, identifying the marker that better expresses the degree of inflammation and which isolate component presents a higher degree of interference on the studied inflammatory markers, in order to identify other important risk factors when determining arterial inflammation. METHODS: A total of 87 hypertensive, diabetic and dyslipidemic patients were selected, aged 26 to 85 years, who met the necessary criteria for the positive diagnosis of MS. The patients were assessed through 24-hour ambulatory blood pressure monitoring (ABPM) and underwent hs-CRP and IL-6 measurements, among other metabolic variables. RESULTS: The patients that presented CRP > 0.3mg/dl showed a significant correlation (p102/88 cm in 83.7%, glycemia > 110mg/dl in 88% and BMI > 30kg/m²in60.5% of the studied individuals. CONCLUSION: We concluded that the CRP was the inflammatory marker with the highest expression regarding the studied variables, with smoking, albuminuria, previous personal history of cardiopathy, BMI, abdominal perimeter and hyperglycemia being the ones with the highest statistical significance. Interleukin-6 did not present a correlation with any of the studied variables.
Context
Prolonged calorie restriction increases life span in rodents. Whether prolonged calorie restriction affects biomarkers of longevity or markers of oxidative stress, or reduces metabolic rate beyond that expected from reduced metabolic mass, has not been investigated in humans.Objective
To examine the effects of 6 months of calorie restriction, with or without exercise, in overweight, nonobese (body mass index, 25 to <30) men and women.Design, Setting, and Participants
Randomized controlled trial of healthy, sedentary men and women (N = 48) conducted between March 2002 and August 2004 at a research center in Baton Rouge, La.Intervention
Participants were randomized to 1 of 4 groups for 6 months: control (weight maintenance diet); calorie restriction (25% calorie restriction of baseline energy requirements); calorie restriction with exercise (12.5% calorie restriction plus 12.5% increase in energy expenditure by structured exercise); very low-calorie diet (890 kcal/d until 15% weight reduction, followed by a weight maintenance diet).Main Outcome Measures
Body composition; dehydroepiandrosterone sulfate (DHEAS), glucose, and insulin levels; protein carbonyls; DNA damage; 24-hour energy expenditure; and core body temperature.Results
Mean (SEM) weight change at 6 months in the 4 groups was as follows: controls, −1.0% (1.1%); calorie restriction, −10.4% (0.9%); calorie restriction with exercise, −10.0% (0.8%); and very low-calorie diet, −13.9% (0.7%). At 6 months, fasting insulin levels were significantly reduced from baseline in the intervention groups (all P<.01), whereas DHEAS and glucose levels were unchanged. Core body temperature was reduced in the calorie restriction and calorie restriction with exercise groups (both P<.05). After adjustment for changes in body composition, sedentary 24-hour energy expenditure was unchanged in controls, but decreased in the calorie restriction (−135 kcal/d [42 kcal/d]), calorie restriction with exercise (−117 kcal/d [52 kcal/d]), and very low-calorie diet (−125 kcal/d [35 kcal/d]) groups (all P<.008). These “metabolic adaptations” (~ 6% more than expected based on loss of metabolic mass) were statistically different from controls (P<.05). Protein carbonyl concentrations were not changed from baseline to month 6 in any group, whereas DNA damage was also reduced from baseline in all intervention groups (P <.005).Conclusions
Our findings suggest that 2 biomarkers of longevity (fasting insulin level and body temperature) are decreased by prolonged calorie restriction in humans and support the theory that metabolic rate is reduced beyond the level expected from reduced metabolic body mass. Studies of longer duration are required to determine if calorie restriction attenuates the aging process in humans.Trial Registration
ClinicalTrials.gov Identifier: NCT00099151
Figures in this Article
Prolonged calorie restriction increases life span in rodents and other shorter-lived species.1 Whether this occurs in longer-lived species is unknown, although the effect of prolonged calorie restriction in nonhuman primates is under investigation. One hypothesis to explain the antiaging effects of calorie restriction is reduced energy expenditure with a consequent reduction in the production of reactive oxygen species (ROS).2- 3 However, other metabolic effects associated with calorie restriction, including alterations in insulin sensitivity and signaling, neuroendocrine function, stress response, or a combination of these, may retard aging.4
Total energy expenditure is made up of resting energy expenditure (50%-80% of energy), the thermic effect of feeding (~10%), and nonresting energy expenditure (10%-40%).5 Whether total energy expenditure is reduced beyond the level expected for a given reduction in the size of the metabolizing mass following calorie restriction is debated. Leibel et al6 showed that a 10% weight loss reduced sedentary 24-hour energy intake for weight maintenance between 15% and 20% in obese patients, suggesting that metabolic adaptation occurs in humans. However, the weight loss was achieved quickly with a liquid diet and, with the exception of several normal-weight patients in the study by Leibel et al, the effects of prolonged calorie restriction on energy expenditure in nonobese humans have not been assessed. In rhesus monkeys, resting energy expenditure adjusted for fat-free mass (FFM) and fat mass was lower after 11 years of calorie restriction.7 Similarly, total energy expenditure was lower in monkeys following 10 years of weight clamping.8 Studies in rodents have proven more controversial with reports of decreased, no change, or increased adjusted energy expenditure in calorie restriction vs ad libitum fed–animals.9- 13
One of the most widely accepted theories of aging is the oxidative stress theory, which hypothesizes that oxidative damage produced by ROS accumulates over time, leading to the development of disease such as cancer, aging, and ultimately death.14 Reactive oxygen species are byproducts of energy metabolism, with 0.2% to 2.0% of oxygen consumption (O2) resulting in ROS formation.15- 16 Reactive oxygen species attack lipids, proteins, and DNA, generating a number of products that affect normal cell functioning.17 Studies in rodents subjected to calorie restriction demonstrate a 30% decrease in 8-oxo-7,8-dihydroguanine (8-oxodG) in brain, skeletal muscle, and heart; similar reductions in carbonyl content in brain and muscle18- 22; and transcriptional patterns that suggest decreased oxidative stress in response to calorie restriction.23 Rhesus monkeys subjected to calorie restriction exhibit divergent responses in the expression of genes involved in oxidative stress.24
Core body temperature and levels of dehydroepiandrosterone sulfate (DHEAS) and insulin are proposed biomarkers of calorie restriction and longevity in rodents and monkeys.25 Data from the Baltimore Longitudinal Study of Aging support the association between longevity and temperature and insulin and DHEAS levels; men with plasma insulin concentration or oral temperature below the median, and DHEAS levels above the median, live longer.26 Furthermore, in a cross-sectional study that compared individuals following self-imposed nutritionally adequate calorie restriction for 6 years with normal-weight controls, Fontana et al27 found that participants in the calorie restriction group had lower levels of serum glucose, insulin, and markers of atherosclerosis.
The aims of this study were to establish whether prolonged calorie restriction by diet alone or in conjunction with exercise can be successfully implemented in nonobese individuals and to determine the effects of the interventions on established biomarkers of calorie restriction, sedentary energy expenditure, and oxidative damage to DNA and proteins.
Three daily portions of whole-grain foods could lower cardiovascular disease risk, but a comprehensive intervention trial was needed to confirm this recommendation.
We aimed to assess the effects of consumption of 3 daily portions of whole-grain foods (provided as only wheat or a mixture of wheat and oats) on markers of cardiovascular disease risk in relatively high-risk individuals.
This was a randomized controlled dietary trial in middle-aged healthy individuals. After a 4-wk run-in period with a refined diet, we randomly allocated volunteers to a control (refined diet), wheat, or wheat + oats group for 12 wk. The primary outcome was a reduction of cardiovascular disease risk factors by dietary intervention with whole grains, which included lipid and inflammatory marker concentrations, insulin sensitivity, and blood pressure.
We recruited a total of 233 volunteers; 24 volunteers withdrew, and 3 volunteers were excluded. Systolic blood pressure and pulse pressure were significantly reduced by 6 and 3 mm Hg, respectively, in the whole-grain foods groups compared with the control group. Systemic markers of cardiovascular disease risk remained unchanged apart from cholesterol concentrations, which decreased slightly but significantly in the refined group.
Daily consumption of 3 portions of whole-grain foods can significantly reduce cardiovascular disease risk in middle-aged people mainly through blood pressure-lowering mechanisms. The observed decrease in systolic blood pressure could decrease the incidence of coronary artery disease and stroke by ≥15% and 25%, respectively. This trial was registered at clinicaltrials.gov as ISRCTN27657880.
Diet is important in the prevention of CVD, and it has been suggested that a diet high in MUFA is more cardioprotective than a low-fat diet. We hypothesised that the thrombotic risk profile is improved most favourably by a high-MUFA diet compared with a low-fat diet. This was tested in a parallel randomised intervention trial on overweight individuals (aged 28·2 (sd 4·6) years) randomly assigned to a diet providing a moderate amount of fat (35-45 % of energy; >20 % of fat as MUFA) (MUFA diet; n 39), to a low-fat (LF; 20-30 % of energy) diet (n 43), or to a control diet (35 % of energy as fat; n 24) for 6 months after a weight loss of about 10 %. Protein constituted 10-20 % of energy in all three diets. All foods were provided free of charge from a purpose-built supermarket. Fasting blood samples were collected before and after intervention and analysed for factor VII coagulant activity (FVII:c), fibrinogen, prothrombin fragment 1+2 (F1+2), D-dimer and plasminogen activator inhibitor (PAI). The fibrinogen concentration was significantly lowered by the LF diet, but not by the MUFA diet. Changes in fibrinogen differed significantly between diet groups. BMI and PAI concentration increased and D-dimer concentrations were reduced irrespective of the diets. No changes were observed for FVII:c and F1+2. Our findings suggest that in overweight subjects after weight loss the thrombotic risk profile is improved most favourably by the LF diet compared with the MUFA diet based on the reduction in fibrinogen concentrations.
Several epidemiological and clinical studies have evaluated the effects of a Mediterranean diet (Med-Diet) on total cardiovascular mortality, and all concluded that adherence to the traditional Med-Diet is associated with reduced cardiovascular risk. However, the molecular mechanisms involved are not fully understood. Since atherosclerosis is nowadays considered a low-grade inflammatory disease, recent studies have explored the anti-inflammatory effects of a Med-Diet intervention on serum and cellular biomarkers related to atherosclerosis. In a pilot study of the PREvencion con DIeta MEDiterranea (PREDIMED) trial, we analysed the short-term effects of two Med-Diet interventions, one supplemented with virgin olive oil and another with nuts, on vascular risk factors in 772 subjects at high risk for CVD, and in a second study we evaluated the effects of these interventions on cellular and serum inflammatory biomarkers in 106 high-risk subjects. Compared to a low-fat diet, the Med-Diet produced favourable changes in all risk factors. Thus, participants in both Med-Diet groups reduced blood pressure, improved lipid profile and diminished insulin resistance compared to those allocated a low-fat diet. In addition, the Med-Diet supplemented with virgin olive oil or nuts showed an anti-inflammatory effect reducing serum C-reactive protein, IL-6 and endothelial and monocytary adhesion molecules and chemokines, whereas these parameters increased after the low-fat diet intervention. In conclusion, Med-Diets down-regulate cellular and circulating inflammatory biomarkers related to atherogenesis in subjects at high cardiovascular risk. These results support the recommendation of the Med-Diet as a useful tool against CVD.
Fruits and vegetables are important sources of fiber and nutrients with a recognized antioxidant capacity, which could have beneficial effects on the proinflammatory status as well as some metabolic syndrome and cardiovascular disease features. The current study assessed the potential relationships of fruit and vegetable consumption with the plasma concentrations and mRNA expression values of some proinflammatory markers in young adults.
One-hundred and twenty healthy subjects (50 men/70 women; 20.8 +/- 2.6 y; 22.3 +/- 2.8 kg/m2) were enrolled. Experimental determinations included anthropometry, blood pressure and lifestyle features as well as blood biochemical and inflammatory measurements. The mRNA was isolated from peripheral blood mononuclear cells (PBMC) and the gene expression concerning selected inflammatory markers was assessed by quantitative real-time PCR. Nutritional intakes were estimated by a validated semi-quantitative food-frequency questionnaire.
The highest tertile of energy-adjusted fruit and vegetable consumption (>660 g/d) was associated with lower plasma concentrations of C-reactive protein (CRP) and homocysteine and with lower ICAM1, IL1R1, IL6, TNFalpha and NFkappaB1 gene expression in PBMC (P for trend < 0.05), independently of gender, age, energy intake, physical activity, smoking, body mass index, systolic blood pressure and circulating non-esterified fatty acids. In addition, plasma CRP, homocysteine and TNFalpha concentrations and ICAM1, TNFalpha and NFkappaB1 gene expression in PBMC showed a descending trend as increased fiber intake (>19.5 g/d) from fruits and vegetables (P for trend < 0.05). Furthermore, the participants within the higher tertile (>11.8 mmol/d) of dietary total antioxidant capacity showed lower plasma CRP and mRNA values of ICAM1, IL1R1, IL6, TNFalpha and NFkappaB1 genes (P for trend < 0.05). The inverse association between fruit and vegetable consumption and study proinflammatory markers followed the same trend and remained statistically significant, after the inclusion of other foods/nutrients in the linear regression models.
A higher fruit and vegetable consumption was independently associated not only with reduced CRP and homocysteine concentrations but also with a lower mRNA expression in PBMC of some relevant proinflammatory markers in healthy young adults.
Weight loss and subsequent body weight maintenance are difficult for obese individuals despite the wide variety of dietary regimens and approaches. A substantial body of scientific evidence has shown that by simply varying the macronutrient distribution and composition of dietary factors, weight losses of varying amounts, longer-term body weight maintenance periods, better appetite regulation, and changes in features of the metabolic syndrome can be achieved. At present, renewed efforts are underway to increase the protein content of weight-loss diets, simultaneously restrict fat consumption to no more than 30%, favor polyunsaturated fat, have carbohydrates account for between 40 and 50% of total energy intake, and promote the consumption of low-glycemic foods. The present article reviews the scientific evidence for the effects of several dietary manipulations and sustainable strategies for weight loss and body weight stability as well as for treating specific features of the metabolic syndrome.
Obesity is the consequence of an imbalance between energy intake and expenditure, food intake being affected by multiple factors -psychological, social, work-related, etc. This revision discusses the role of diet in the behavioural treatment (BT) of obesity, which faces multiple approaches and focuses on patients' behaviour rather than their mere energy intake.
Recent literature has been revised that deals with the health benefits of Mediterranean diet in order to assess its suitability for obesity treatment based on BT.
BT helps patients to develop skills and techniques in order to adopt proper habits and attain their healthiest weight. Patients learn to establish realistic goals, both as regards weight and behaviour, and to evaluate their progress in modifying eating and exercising habits. The application of the Mediterranean diet in obesity treatment presents various advantages which are based on the principles of this diet -wide variety of food, high carbohydrate content, or high satiating capacity, which prevents specific hunger and ketogenesis-, and has been demonstrated to be effective in reducing body weight.
BT based on the Mediterranean diet is a useful tool for obesity treatment. The Mediterranean diet provides the patients with a diet established on widely recognised nutritional benefits, suitable to their social and daily life, and that can be easily followed in the long term, according to the objectives of BT. For these reasons, Mediterranean diet-based BT helps to prolong both the treatment and maintenance periods and therefore contributes to a more stable weight loss.
Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development.
It was hypothesized that specific dietary components are able to reduce low-grade inflammation as well as metabolic and oxidative stress.
Dietary products [resveratrol, green tea extract, alpha-tocopherol, vitamin C, n-3 (omega-3) polyunsaturated fatty acids, and tomato extract] selected for their evidence-based antiinflammatory properties were combined and given as supplements to 36 healthy overweight men with mildly elevated plasma C-reactive protein concentrations in a double-blind, placebo-controlled, crossover study with treatment periods of 5 wk. Inflammatory and oxidative stress defense markers were quantified in plasma and urine. Furthermore, 120 plasma proteins, 274 plasma metabolites (lipids, free fatty acids, and polar compounds), and the transcriptomes of peripheral blood mononuclear cells and adipose tissue were quantified.
Plasma adiponectin concentrations increased by 7%, whereas C-reactive protein (principal inflammation marker) was unchanged. However, a multitude of subtle changes were detected by an integrated analysis of the "omics" data, which indicated modulated inflammation of adipose tissue, improved endothelial function, affected oxidative stress, and increased liver fatty acid oxidation.
An intervention with selected dietary products affected inflammatory processes, oxidative stress, and metabolism in humans, as shown by large-scale profiling of genes, proteins, and metabolites in plasma, urine, and adipose tissue. This trial was registered at clinical trials.gov as NCT00655798.
Mass spectrometry (MS) techniques, because of their sensitivity and selectivity, have become methods of choice to characterize the human metabolome and MS-based metabolomics is increasingly used to characterize the complex metabolic effects of nutrients or foods. However progress is still hampered by many unsolved problems and most notably the lack of well established and standardized methods or procedures, and the difficulties still met in the identification of the metabolites influenced by a given nutritional intervention. The purpose of this paper is to review the main obstacles limiting progress and to make recommendations to overcome them. Propositions are made to improve the mode of collection and preparation of biological samples, the coverage and quality of mass spectrometry analyses, the extraction and exploitation of the raw data, the identification of the metabolites and the biological interpretation of the results.
The present report discusses targeted and non-targeted approaches to monitor single nutrients and global metabolite profiles in nutritional research. Non-targeted approaches such as metabolomics allow for the global description of metabolites in a biological sample and combine an analytical platform with multivariate data analysis to visualise patterns between sample groups. In nutritional research metabolomics has generated much interest as it has the potential to identify changes to metabolic pathways induced by diet or single nutrients, to explore relationships between diet and disease and to discover biomarkers of diet and disease. Although still in its infancy, a number of studies applying this technology have been performed; for example, the first study in 2003 investigated isoflavone metabolism in females, while the most recent study has demonstrated changes to various metabolic pathways during a glucose tolerance test. As a relatively new technology metabolomics is faced with a number of limitations and challenges including the standardisation of study design and methodology and the need for careful consideration of data analysis, interpretation and identification. Targeted approaches are used to monitor single or multiple nutrient and/or metabolite status to obtain information on concentration, absorption, distribution, metabolism and elimination. Such applications are currently widespread in nutritional research and one example, using stable isotopes to monitor nutrient status, is discussed in more detail. These applications represent innovative approaches in nutritional research to investigate the role of both single nutrients and diet in health and disease.
The psychological effects of dieting and weight loss have been an area of controversy in obesity. As part of a large multicenter study involving 1944 obese subjects seeking treatment at Italian medical centers, we investigated the effects of weight loss on psychological distress and binge eating in 500 subjects remaining in continuous treatment at different centers with slightly different strategies (78.8% females; age: M=46.2 years, SD=10.8; BMI: M=37.3 kg/m(2), SD=5.6). At baseline and after 12 months all subjects were evaluated by the Symptom CheckList-90 Global Severity Index (SCL-GSI) and by the Binge Eating Scale (BES). In both males and females, weight loss was associated with improved psychometric testing. Changes in SCL-GSI were associated with changes in BMI (beta=0.13; t=2.85; p<0.005), after adjustment for age, gender, initial BMI and center variability. Similarly, BES changes were associated with BMI change (beta=0.15; t=3.21; p<0.001). We conclude that in subjects compliant to follow-up a successful management of obesity, not directly addressing psychological distress, is associated with a significant improvement of both psychological distress and binge eating, linearly related to the amount of weight loss, independently of treatment procedures.