[Show abstract][Hide abstract] ABSTRACT: The fact that gastric surgery is at the moment the most effective treatment to fight against obesity highlights the relevance of gastric derived proteins as potential targets to treat this pathology. Taking advantage of a previously established gastric explant model for endocrine studies, the proteomic analysis of gastric secretome was performed. To validate this gastric explant system for proteomic analysis, the identification of ghrelin, a classical gastric derived peptide, was performed by MS. In addition, the differential analysis of gastric secretomes under differential nutritional status (control feeding vs fasting vs re-feeding) was performed. The MS identified proteins are showed in the present manuscript. The data supplied in this article is related to the research article entitled “Comparative secretome analysis of rat stomach under different nutritional status”
[Show abstract][Hide abstract] ABSTRACT: Context: Low testosterone (T) has been associated with incident metabolic syndrome (MetS), but it remains unclear if this association is independent of sex hormone binding globulin (SHBG). Estradiol (E2) may also be associated with MetS, but few studies have investigated this. Objective: To study the association between baseline sex steroids and the development of incident MetS and to investigate the influence of SHBG, BMI and insulin resistance on this risk. Methods: 3369 community-dwelling men aged 40-79 years were recruited for participation in EMAS. MetS was defined by the updated NCEP ATP III criteria. Testosterone and E2 levels were measured by liquid and gas chromatography/mass spectrometry respectively. Logistic regression was used to assess the association between sex steroids and incident MetS. Results: 1651 men without MetS at baseline were identified. During follow-up 289 men developed incident MetS, while 1362 men did not develop MetS. Men with lower baseline total T levels were at higher risk for developing MetS (Odds ratio (OR)=1.72, p<0.001), even after adjustment for SHBG (OR=1.43, p=0.001), BMI (OR=1.44, p<0.001) or HOMA-IR (OR=1.64, p<0.001). E2 was not associated with development of MetS (OR=1.04; p=0.56). However, a lower E2/T ratio was associated with a lower risk of incident MetS (OR=0.38; p<0.001), even after adjustment for SHBG (OR=0.48; p<0.001), BMI (OR=0.60; p=0.001) or HOMA-IR (OR=0.41; p<0.001). Conclusions: In men, lower T levels, but not E2, are linked with an increased risk of developing MetS, independent of SHBG, BMI or insulin resistance. A lower E2/T ratio may be protective against developing MetS.
The Journal of clinical endocrinology and metabolism. 01/2015;
[Show abstract][Hide abstract] ABSTRACT: Objective: A number of factors can influence the reported outcomes of transsphenoidal surgery (TSS) for Cushing's disease - including different remission and recurrence criteria, for which there is no consensus. Therefore, a comparative analysis of the best treatment options and patient management strategies is difficult. In this review, we investigated the clinical outcomes of initial TSS in patients with Cushing's disease based on definitions of and assessments for remission and recurrence. Methods: We systematically searched PubMed and identified 44 studies with clear definitions of remission and recurrence. When data were available, additional analyses by time of remission, tumour size, duration of follow-up, surgical experience, year of study publication, and adverse events related to surgery were performed. Results: Of the 44 articles selected, only one reported endoscopic TSS. Data from a total of 6,400 patients who received microscopic TSS were extracted and analysed. A variety of definitions of remission and recurrence of Cushing's disease after initial microscopic TSS was used, giving broad ranges of remission (42.0-96.6%; median, 77.9%) and recurrence (3.1-47.4%; median, 11.5%). Better remission and recurrence outcomes were achieved for micro- versus macroadenomas; however, no correlations were found with other parameters, other than improved safety with longer surgical experience. Conclusions: The variety of methodologies used in clinical evaluation of TSS for Cushing's disease strongly support the call for standardization and optimization of studies to inform clinical practice and maximize patient outcomes. Clinically significant rates of failure of initial TSS highlight the need for effective second-line treatments.
European journal of endocrinology / European Federation of Endocrine Societies. 01/2015;
[Show abstract][Hide abstract] ABSTRACT: Obesity is a major public health threat for many industrialised countries. Bariatric surgery is the most effective treatment against obesity, suggesting that gut derived signals are crucial for energy balance regulation. Several descriptive studies have proven the presence of gastric endogenous systems that modulate energy homeostasis; however, these systems and the interactions between them are still not well known. In the present study, we show for the first time the comparative 2-DE gastric secretome analysis under different nutritional status. We have identified 38 differently secreted proteins by comparing stomach secretomes from tissue explant cultures of rats under feeding, fasting and re-feeding conditions. Among the proteins identified, glyceraldehyde-3-phosphate dehydrogenase was found to be more abundant in gastric secretome and plasma after re-feeding, and downregulated in obesity. Additionally, two calponin-1 species were decreased in feeding state, and other were modulated by nutritional and metabolic conditions. These and other secreted proteins identified in this work may be considered as potential gastrokines implicated in food intake regulation.
Journal of Proteomics 01/2015; · 3.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Lipodystrophies are a group of diseases mainly characterized by a loss of adipose tissue and frequently associated with insulin resistance, hypertriglyceridemia, and hepatic steatosis. In uncommon lipodystrophies, these complications frequently are difficult to control with conventional therapeutic approaches. This retrospective study addressed the effectiveness of recombinant methionyl leptin (metreleptin) for improving glucose metabolism, lipid profile, and hepatic steatosis in patients with genetic lipodystrophic syndromes. We studied nine patients (five females and four males) with genetic lipodystrophies [seven with Berardinelli-Seip syndrome, one with atypical progeroid syndrome, and one with type 2 familial partial lipodystrophy (FPLD)]. Six patients were children under age 9 years, and all patients had baseline triglycerides levels >2.26 mmol/L and hepatic steatosis; six had poorly controlled diabetes mellitus. Metreleptin was self-administered subcutaneously daily at a final dose that ranged between 0.05 and 0.24 mg/(kg day) [median: 0.08 mg/(kg day)] according to the body weight. The duration of treatment ranged from 9 months to 5 years, 9 months (median: 3 years). Plasma glucose, hemoglobin A1c (Hb A1c), lipid profile, plasma insulin and leptin, and hepatic enzymes were evaluated at baseline and at least every 6 months. Except for the patient with FPLD, metreleptin replacement significantly improved metabolic control (Hb A1c: from 10.4 to 7.1 %, p < 0.05). Plasma triglycerides were reduced 76 % on average, and hepatic enzymes decreased more than 65 %. This study extends knowledge about metreleptin replacement in genetic lipodystrophies, bearing out its effectiveness for long periods of time.
[Show abstract][Hide abstract] ABSTRACT: Objective
Meal duration may influence cardiometabolic health. The aim of this study was to explore postprandial effects of meal duration on human metabolism and appetite.DesignPostprandial comparisons following a standard meal eaten slowly over 40-minutes (‘D40’) and the same meal eaten quickly over 10-minutes (‘D10’) on a different day. Each participant therefore acted as their own control, thereby limiting confounding factors.PatientsObese pre-menopausal Caucasian women (n=10) with confirmed normoglycaemia were recruited from an Obesity clinic at UHCW, Coventry UK. Subjects underwent whole-body calorimetry (8-hours) on two separate days.MeasurementsFollowing standard lunch (D40 vs D10), 4-hour postprandial analysis included thermic effect of food (TEF) and bloods taken at pre-defined times (including baseline fasting). Analytes included lipid-profile, adiponectin, insulin, glucose, ghrelin, leptin, endotoxin, gut and pancreatic hormones. Appetite was measured using visual-analogue scales and ad libitum food intake at subsequent meal. Paired-sample t-tests (including area under the curve [AUC]) were used to compare D40 and D10 trials.ResultsPostprandial TEF (over 240-minutes) was significantly greater for D40 than D10 (mean [SEM]: 80.9Kcal [3.8] versus 29.9Kcal [3.4]; 10.6% versus 3.9% respectively, P=0.006; AUC 71.7Kcal.hr versus 22.4Kcal.hr respectively, P=0.02). Postprandial plasma NEFA was significantly lower and adiponectin levels were significantly higher for D40 than D10 (AUC [SEM]: NEFA 627μmol.hr/l  vs 769μmol.hr/l  respectively, P=0.02; adiponectin 33.4μg.hr/ml [3.9] vs 27.3μg.hr/ml [3.8] respectively, P=0.04). Other postprandial analytes and appetite measures were equivalent.Conclusions
In obese women, eating slowly associates with enhanced TEF, elevated serum adiponectin and suppressed NEFA.This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: The results of using HbA1C-based criteria for diagnosis of type 2 diabetes and prediabetes have been reported to differ from those obtained using fasting plasma glucose (FPG) or an oral glucose tolerance test (OGTT). We aimed to determine whether these discrepancies might be due to the influence of the glycation gap.
[Show abstract][Hide abstract] ABSTRACT: Background: Social and lifestyle influences on age-related changes in body morphology are complex because lifestyle and physiological response to social stress can affect body fat differently. Objective: We examined the associations of socioeconomic status (SES) and lifestyle factors with body mass index (BMI) and waist circumference (WC) in middle-aged and elderly European men. Design and setting: Cross-sectional study of 3,319 men aged 40-79 recruited from eight European centres. Outcomes: We estimated relative risk ratios (RRRs) of overweight/obesity associated with unfavourable SES and lifestyles. Results: The prevalence of BMI30kg/m2 or WC102cm rose linearly with age, except in the 8th decade when high BMI, but not high WC, declined. Among men aged 40-59y, compared to non-smokers or most active men, centre and BMI adjusted RRRs for having a WC between 94-101.9cm increased by 1.6-fold in current smokers, and 2.7-fold in least active men, maximal at 2.8-fold in least active men who smoked. Similar patterns but greater RRRs were observed for men with WC≥102cm, notably 8.4-fold greater in least active men who smoked. Compared to men in employment, those who were not in employment had increased risk of having a high WC by 1.4-fold in the 40-65y group and by 1.3-fold in the 40-75y group. These relationships were weaker among elderly men. Conclusion: Unfavourable SES and lifestyles associate with increased risk of obesity, especially in middle-aged men. The combination of inactivity and smoking was the strongest predictor of high WC, providing a focus for health promotion and prevention at an early age.
European Journal of Endocrinology 10/2014; · 3.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Endocannabinoids and temperament traits have been linked to both physical activity and body mass index (BMI) however no study has explored how these factors interact in females. The aims of this cross-sectional study were to 1) examine differences among distinct BMI groups on daytime physical activity and time spent in moderate-vigorous physical activity (MVPA), temperament traits and plasma endocannabinoid concentrations; and 2) explore the association and interaction between MVPA, temperament, endocannabinoids and BMI.
PLoS ONE 08/2014; 9(8):e104534. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background Androgens acting via the androgen receptor (AR) stimulate production of prostate specific antigen (PSA), which is a clinical marker of prostate cancer (PCa). Since genetic variants in the AR may have a significant impact on the risk of being diagnosed with PCa, the aim was to investigate if AR-variants were associated with the risk of having PSA above clinically used cut-off thresholds of 3 or 4 ng/mL in men without PCa. Methods Men without PCa history (n=1744) were selected from the European Male Ageing Study (EMAS) cohort of 40-80 year old men from 8 different European centers. Using linear and logistic regression models, with age and center as covariates, we investigated whether AR-variants (CAG repeat-length and/or SNP genotype) were associated with having serum PSA concentrations above 3 or 4 ng/mL, which often are set as cut-off concentrations for further investigation of PCa. Results Carriers of the SNP rs1204038 A-allele (16% of the men) were more likely to have PSA>3 and 4 ng/mL (OR; 95%CI 1.65; 1.13-2.40 and 1.87; 1.18-2.96, respectively) than G-allele carriers. They also had shorter CAG-repeats (median 20 vs. 23, p<0.0005), but CAG repeat length per se did not affect the PSA concentrations. Conclusion The A-allele of the SNP rs1204038 gives a 65% higher risk of having PSA above 3 ng/mL than the G-allele in men without PCa, and thereby an increased risk of being referred for further examination on suspicion of PCa. Impact Serum PSA as a clinical marker could be improved by adjustment for AR-genotype.
[Show abstract][Hide abstract] ABSTRACT: Background: Both low total testosterone (T) and sex hormone binding globulin (SHBG) have been associated with an increased risk for metabolic syndrome (MetS) in men. However, serum concentrations of T are strongly linked to SHBG levels, and both are decreased in MetS. Whether the risk for MetS associated with low T is independent of SHBG, remains unclear. Furthermore, T is aromatised to estradiol (E2). The potential impact of variations in E2 on the risk for MetS has not been investigated.
Objective: To study the longitudinal association of T and E2 and the risk for MetS in a large European cohort of healthy middle aged and elderly men and to assess if this risk is independent of SHBG.
Methods: The European Male Ageing Study (EMAS) included 2736 community-dwelling men from 8 European countries, aged 40-79 years at baseline, followed-up for 4.3 years (range 2.95-5.7 years). MetS was defined using the ATP III criteria. Serum total T and E2 levels were measured by respectively liquid and gas chromatography/mass spectrometry. The association between baseline SHBG and sex steroids and the development of incident MetS at follow-up was assessed using logistic regression with adjustments made for age, study centre, smoking status, physical activity and general health. Results were expressed as standardised odds ratios (OR) with 95% confidence intervals (CI).
Results: In the EMAS cohort, 282 men developed MetS between baseline and follow up, while 1387 men did not satisfy criteria for MetS at either time point. Men with a higher level of SHBG or total T had a significantly lower risk of developing MetS (OR 0.59 (CI 0.49-0.70, p˂0.001) and 0.58 (CI 0.50-0.68, p˂0.001), respectively). Calculated free T showed similar findings to total T. E2 was not associated with incident MetS (OR 0.99, CI 0.86-1.13, p=0.867). However, the T/E2 ratio was strongly inversely associated with incident MetS (OR 0.55, CI 0.46-0.66, p˂0.001). The inverse association between MetS and SHBG became non-significant if T was added to the model (OR 0.80, CI 0.64-1.01, p=0.064), while the association with T persisted after addition of SHBG (OR 0.67, CI 0.55-0.83). The association between E2 and incident MetS remained non-significant after adjustment for SHBG (OR 1.14, CI 0.99-1.32, p=0.074), but became significant after adjustment for T (OR 1.40, CI 1.20-1.64, p˂0.001). The T/E2 ratio remained strongly inversely associated with incident MetS even after SHBG was added to the model (OR 0.62, CI 0.51-0.75, p˂0.001).
Conclusions: In men, low T, independently of SHBG and E2, predicts the development of MetS. A higher T/E2 ratio, reflecting lower aromatisation of T into E2, is linked with a reduced risk for MetS.
[Show abstract][Hide abstract] ABSTRACT: The global prevalence of obesity has significantly increased in most industrialized countries. Anti-obesity drugs are scarce, and indications to change their life style are impractical. Therefore, to identify diets able to produce significantly and maintained weight loss is mandatory. The present work evaluated the efficacy of a very low-calorie-ketogenic (VLCK) diet in obesity. A group of obese patients were randomized into two groups: the VLCK diet group and a standard low-calorie diet (LC group). The follow-up period was 12 months. Both groups received external support, counseling, to perform physical activity and adhered to the diet. The VLCK diet induced a 30-45 days of mild ketosis and significant effects on body weight within 15 days. At 2 months, the weight reductions in the VLCK diet and LC diet groups were 13.6 ± 3.9 and 4.8 ± 2.7 kg, respectively (p < 0.0001). At the end of the study, at 12 months, the weight reductions were 19.9 ± 12.3 and 7.0 ± 5.6 kg, respectively (p < 0.0001), and more than 88 % of patients in the VLCK diet group lost more of 10 % of their initial weight. Lean mass was practically unaffected. The VLCK diet was well tolerated and the side effects were moderate and transitory. In a group of obese patients, the VLCK diet was significantly more effective than a standard LC diet. At one year follow-up in the group with VLCK diet, most of the patients loss more than 10 % of their initial weight and lean mass was well preserved.
[Show abstract][Hide abstract] ABSTRACT: FNDC5/irisin protein has been recently postulated as beneficial in the treatment of
obesity and diabetes because it is induced by exercise and is able to increase energy
expenditure. However, recent reports have shown that WAT also secretes irisin, and
that circulating irisin is elevated in obese subjects. The aim of this study was to
evaluate the circulating levels of irisin in conditions of extreme BMI, such as anorexia
and obesity, and the correlations of irisin with basal metabolism and daily activity.
Materials and methods: The study involved 145 female patients, including 96
patients with extreme BMIs [30 anorexic (AN) and 66 obese (OB) patients] and 49
healthy normal weight control patients (NW) to assess the circulating irisin levels.
Biochemical, anthropometric and body composition measurements, daily physical
activity and resting energy expenditure (REE) were analysed in the subjects.
Results: The plasma irisin levels were significantly elevated in the OB patients
compared with the AN and NW patients. Irisin also correlated positively with body
weight, BMI and fat mass. The OB patients exhibited the highest REE and higher
daily physical activity compared with the AN patients but lower activity compared with
the NW patients. The irisin levels were inversely correlated with daily physical activity
and directly correlated with REE. Fat mass contributed to most of the variability of the
irisin plasma levels independently of the other studied parameters.
Conclusions: Irisin plasma levels are influenced by energy expenditure
independently of daily physical activity but fat mass is the main contributing factor
International Journal of Endocrinology 02/2014; 2014. · 1.52 Impact Factor
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[Show abstract][Hide abstract] ABSTRACT: In March 2013, the Acromegaly Consensus Group met to revise and update guidelines for the medical treatment of acromegaly. The meeting comprised experts skilled in the medical management of acromegaly. The group considered treatment goals covering biochemical, clinical and tumour volume outcomes, and the place in guidelines of somatostatin receptor ligands, growth hormone receptor antagonists and dopamine agonists, and alternative modalities for treatment including combination therapy and novel treatments. This document represents the conclusions of the workshop consensus.
[Show abstract][Hide abstract] ABSTRACT: Objectives: Eating styles have been studied in both obesity (OB) and eating disorders (ED), but they have not been examined in these two weight conditions together. The present study explores differences in eating styles in an Anorexia Nervosa (AN) and OB sample, compared to healthy controls (HC), and it analyses their relationship with Body Mass Index (BMI) and personality traits. Method: The total sample consisted of 291 female participants (66 AN, 79 OB and 146 HC). Evaluation: Assessment measures included the Dutch Eating Behaviour Questionnaire -DEBQ- and the Temperament and Character Inventory–revised -TCI-R-. Results: The MANCOVA test showed significant differences among the three groups for all eating styles, with emotional eating being more typical in the OB group and restrained eating more typical in the AN group. Partial correlation analyses showed relationships between emotional and external eating and BMI, as well as relationships with different temperament and character traits. The stepwise discriminant function analysis showed that the DEBQ correctly classified 65.6% of the sample into the three weight categories; when combined with the TCI-R, correct classification increased to 72.6%. Conclusions: Weight conditions showed different eating behaviour patterns. Temperament and character traits were related to eating behaviours. DEBQ and TCI-R were able to discriminate between groups. Differences in eating styles in the weight groups can have implications for understanding the development and maintenance of OB and ED.
[Show abstract][Hide abstract] ABSTRACT: Cushing's disease is a rare chronic disease caused by a pituitary adenoma, which leads to excess secretion of adrenocorticotropic hormone (ACTH). The over-production of ACTH leads to hyperstimulation of the adrenal glands and a chronic excess of cortisol, resulting in the signs and symptoms of a severe clinical state (Cushing's syndrome) that leads to significant morbidity, negative impacts on the patient's quality of life, and, if untreated, increased mortality. The management of patients with Cushing's disease is complicated by the heterogeneity of the condition, with signs and symptoms that overlap with those of other diseases, and high subclinical incidence rates. Controversies surrounding the tests used for screening and identifying patients with Cushing's disease add to the challenge of patient management. Surgical intervention to remove the adenoma is the first-line treatment for patients with Cushing's disease, but medical therapies are useful in patients who relapse or are unsuitable for surgery. The recent introduction of pasireotide, the first pituitary-directed medical therapy, expands the number of treatment options available for patients with Cushing's disease. This state-of-the-art review aims to provide an overview of the most recent scientific research and clinical information regarding Cushing's disease. Continuing research into improving the diagnosis and treatment of Cushing's disease will help to optimize patient management.