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The various studies have examined the relationship between FTO gene expression and macronutrients levels. In order to obtain better viewpoint from this interactions, all of existing studies were reviewed systematically. All published papers have been obtained and reviewed using standard and sensitive keywords from databases such as CINAHL, Embase, PubMed, PsycInfo, and the Cochrane, from 1990 to 2016. The results indicated that all of 6 studies that met the inclusion criteria (from a total of 428 published article) found FTO gene expression changes at short-term follow-ups. Four of six studies found an increased FTO gene expression after calorie restriction, while two of them indicated decreased FTO gene expression. The effect of protein, carbohydrate and fat were separately assessed and suggested by all of six studies. In Conclusion, The level of FTO gene expression in hypothalamus is related to macronutrients levels. Future research should evaluate the long-term impact of dietary interventions.
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Review Article
Macronutrients and the FTO gene expression in hypothalamus; a
systematic review of experimental studies
Saeid Doaei
a
, Naser Kalantari
b
, Nastaran Keshavarz Mohammadi
c
,
Ghasem Azizi Tabesh
d
, Maryam Gholamalizadeh
e,
*
a
Students Research Committee, National Nutrition and Food Technology Research Institute, Faculty of Nutrition Sciences and Food Technology, Shahid
Beheshti University of Medical Sciences, Tehran, Iran
b
Department of Community Nutrition, Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
c
Department of Public Health, Faculty of Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
d
Department of Human Genetics, Faculty of Human Genetics, Tehran University of Medical Sciences, Tehran, Iran
e
Students Research Committee, Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
ARTICLE INFO
Article history:
Received 28 May 2016
Accepted 17 January 2017
Available online 24 January 2017
Keywords:
Obesity
Gene expression
FTO
Macronutrients
ABSTRACT
The various studies have examined the relationship between FTO gene expression and macronutrients
levels. In order to obtain better viewpoint from this interactions, all of existing studies were reviewed
systematically. All published papers have been obtained and reviewed using standard and sensitive
keywords from databases such as CINAHL, Embase, PubMed, PsycInfo, and the Cochrane, from 1990 to
2016. The results indicated that all of 6 studies that met the inclusion criteria (from a total of 428
published article) found FTO gene expression changes at short-term follow-ups. Four of six studies found
an increased FTO gene expression after calorie restriction, while two of them indicated decreased FTO
gene expression. The effect of protein, carbohydrate and fat were separately assessed and suggested by all
of six studies. In Conclusion, The level of FTO gene expression in hypothalamus is related to
macronutrients levels. Future research should evaluate the long-term impact of dietary interventions.
© 2017 Published by Elsevier B.V. on behalf of Cardiological Society of India. This is an open access article
under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Contents
1. Introduction . . .................................................................................................... 278
2. Methodology . .................................................................................................... 278
2.1. Data sources ................................................................................................ 278
2.2. Data extraction . . . ........................................................................................... 278
2.3. Outcome variables ........................................................................................... 278
2.4. Intervention components ...................................................................................... 279
2.5. Assessment of methodological rigor ............................................................................. 279
3. Results . . ........................................................................................................ 279
3.1. Components of effective interventions . . ......................................................................... 279
3.2. Effect of calorie restriction . . . .................................................................................. 279
3.3. Effect of increased dietary fat .................................................................................. 279
3.4. Effect of amino acids . . ....................................................................................... 279
3.5. Effect of carbohydrates . ....................................................................................... 279
4. Discussion ........................................................................................................ 280
Disclosure ........................................................................................................ 280
References . . . .................................................................................................... 280
* Corresponding author.
E-mail address: mgholamalizadeh84@yahoo.com (M. Gholamalizadeh).
http://dx.doi.org/10.1016/j.ihj.2017.01.014
0019-4832/© 2017 Published by Elsevier B.V. on behalf of CardiologicalSociety of India. This is an open access article under the CC BY-NC-ND license (http://creativecommons.
org/licenses/by-nc-nd/4.0/).
Indian Heart Journal 69 (2017) 277281
Contents lists available at ScienceDirect
Indian Heart Journal
journal homepage: www.elsevier.com/locate/ihj
1. Introduction
Obesity is a major public health challenge worldwide in 21
century.
1
Obesity has important role in a large number of diseases,
including coronary heart disease, type 2 diabetes, cancer,
hypertension, dyslipidemia and stroke.
25
The prevalence rates
of overweight and Obesity are worriedly increasing in the
worldwide. More than 12% of the adult population are obese.
6
Obese adolescents were reached from 5% to 21% from 1980 to
2012.
7
The role of various factors in the formation and progression of
obesity has been shown. Genetics, life style and environmental
factors are the most important factors that have been associated
with obesity.
8
Numerous studies have reported that unhealthy
lifestyle including low physical activity and poor nutrition are the
main cause of obesity
913
and, therefore, suggested lifestyle
changes as strategies to prevent and combat obesity.
1419
On the
other hand it has also been noticed that even with lifestyle
changes, the success rate in reducing obesity is not always
satisfactory.
20
Here the role of genetics in obesity is highlighted as
an explanation to this dilemma. The results of recent studies in the
eld of nutritional genomics create uncertainties in understanding
the role and importance of lifestyle in occurring obesity and/or
decrease imagined role of the lifestyle in obesity.
Severalstudies have exploredthe interactions betweengenomics
and diet and its relationship with hyperlipidemia and
hypertension.
2125
Recentstudies in the eld of nutritional genomics
have demonstrated that geneticbackground plays an important role
not only in probability of occurring obesity but also in people's
response to the lifestyle intervention.
2634
Several genes have been
studied in relationto obesity, whichone of the most important genes
is FTO (Fat mass and obesity-associated protein).
FTO gene expression is associated with regulation of foodintake
and energy balance.
3541
Also recent studies have tried to explore
the interaction of dietary components with FTO gene expression in
hypothalamus. As there is no systematic review on these studies,
this study aims to ll this gap and contribute to better
understanding of the interaction of dietary components and FTO
gene expression.
2. Methodology
2.1. Data sources
This systematic review was conducted and reported in
accordance with the Preferred Reporting Items for Systematic
Reviews and Meta-Analyses guidelines that have been used for
other gene expression-related systematic reviews.
42
The search
covered all available research from January 1990 to January 2016 in
CINAHL, Embase, PubMed, PsycINFO, and the Cochrane Library. The
bibliographies of included articles were hand-searched, and
promising titles were reviewed in order to locate articles not
catalogued in the major databases. In cases that reviewer was
unable to determine whether an article pertained to the study by
title, the abstract was reviewed. The search terms used were (Body
Mass Index OR Body Weight OR Obesity OR Overweight OR obese
OR FTO gene OR FTO gene expression OR hypothalamus OR diet OR
dietary component OR calorie OR calorie restriction OR protein OR
carbohydrate OR fat OR macronutrient.
This systematic review compares randomized controlled trials
studies that utilized dietary interventions including dietary
macronutrients modications as interventions to change the level
of FTO gene expression. This review involves assessing dietary
interventions delivered through changes in macronutrients levels
to inuence on FTO gene expression. Inclusion criteria consisted of:
randomized trials or trials without randomization or a control
group; a primary outcome including FTO gene expression; trials
that tested dietary interventions (through diet modication) and
subjects included rats and mice. Papers were excluded if the
articles were published in a language other than English.
2.2. Data extraction
The studies focused primarily on changes in calorie,
3639
fat,
37,40
amino acid (Leucine),
36,41
and carbohydrate (Sucrose)
intake or administration.
37,39
2.3. Outcome variables
The initial search generated a total of 428 papers from all the
search databases. To obtain rigorous scientic evidence, only
randomized controlled trials studies were selected for this
systematic review in terms of key outcomes and interventions
used. One reviewer screened the study title and abstract as the rst
screening stage and narrowed the articles to 334 papers. Two
reviewers then reviewed the abstract and narrowed the search
from 334 articles to 85 articles by eliminating duplicate papers
based on the same research. Articles that were nonintervention
studies, such as review papers, and cross-sectional studies were
also excluded. The primary outcome was change of FTO gene
expression with the use of macronutrients. Studies that did not
target FTO gene expression and were not macronutrients-based
Table 1
Methodological rigor of included studies.
Reference Randomization Blinding Inclusion/exclusion
criteria clearly
described
Adequate sample
sizecalculationsshown
Adequate
control
group*
Standard
measures
described
Comparison of baseline
parameters of completers
versusnoncompleters
80%
retention
rate**
MR
score
Gutierrez-
Aguilar
et al.
41
001 1 111 16
Olszewski
et al.
37
001 1 111 16
Boender
et al.
38
001 1 111 16
Johansson
et al.
42
101 1 111 17
Fredriksson
et al.
39
101 1 111 17
Poritsano
et al.
40
101 1 111 17
Notes: *Control group was reective of study group in number, age and sex; **80% of participants completed the intervention.
Abbreviations: MR: methodological rigor.
278 S. Doaei et al. / Indian Heart Journal 69 (2017) 277281
were excluded. Based on the inclusion criteria, two reviewers
examined the full papers and identied 6 studies that met the
inclusion criteria (see Table 1).
2.4. Intervention components
Detailed examination of the following components of effective
interventions was conducted: macronutrient intake or adminis-
tration, method used for intake/administration changes, subjects,
and duration of the intervention. The effectiveness of the
intervention was determined by reviewing the results of the
study and reporting the study ndings.
2.5. Assessment of methodological rigor
Methodological rigor assessment was adapted to include
articles from those in use by the Cochrane Effective Practice and
Organization of Care Review Group and recent systematic
reviews.
42
The eight criteria were scored objectively using
published data and reect potential bias (see Table 1). Studies
were rated independently by two reviewers. Each item was rated
as yes(1), no(0), or not applicable. A total methodological
quality score (ranging from 0 to 8) was calculated by summing up
all yesitems. Studies were rated as having good methodological
quality if they met at least 75% of the criteria (six of eight items).
3. Results
3.1. Components of effective interventions
Two protein-based interventions, two fat-based interventions
and two carbohydrate-based interventions were included in this
systematic review. All of 6 studies indicated the effectiveness of
macronutrients on FTO gene expression.
3.2. Effect of calorie restriction
Four of six studies found that macronutrients intake decreased
FTO gene expression (36, 37, 38 and 40) and two study reported
that 48-h food deprivation had reduced FTO gene expression (39
and 41).
3.3. Effect of increased dietary fat
Two of the six studies that examined the impact of increased
dietary fat found reduced FTO gene expression after interven-
tion.
38,41
For instance, a study by Gutierrez-Aguilar et al.
40
on
tailored high fat diet interventions for Wistar male rats found a
signicant decrease in FTO gene expression at 6 weeks post
intervention. Although, Boender et al. reported a non-signicant
reduction of FTO expression after 8-day high-fat diet.
37
3.4. Effect of amino acids
Two studies assessed the impact of amino acid (ie, Leucine) on
gene expression outcome.
36,41
Olszewski et al. found that
anorexigenic Leucine had reduced FTO gene expression in
organotypic cultures of the hypothalamus at 48 h post interven-
tion.
36
While Johansson et al. found that Leucine intake had
increased FTO gene expression at 48 h post intervention.
41
3.5. Effect of carbohydrates
Two studies assessed the impact of carbohydrate administra-
tion on gene expression outcome. Poritsano et al.
39
found that
increased glucose administration had increased FTO gene expres-
sion at 48 h post intervention. While Boender et al.
37
reported that
increased sucrose intake had insignicantly reduced FTO gene
expression at 8 days post intervention. Also, Olszewski et al. found
Table 2
Summary of Study description.
Reference Study design Sample
characteristic
Intervention/control/
components
Intervention
duration
Results
Dietary fat
Gutierrez-
Aguilar
et al.
40
Experimental 30 rats
(15 animals per
group)
Group 1) High fat diet
Group 2) normal diet
6 weeks FTO gene expression was reduced in the high fat group
Boender
et al.
37
Experimental 24 rats
(12 rats per
group)
Group 1) High fat and
high sucrose diet
Group 2) restricted
feeding
Group 3) Normal diet
8 days FTO gene expression was increased in restricted feeding group
Amino acids
Olszewski
et al.
36
Experimental 14 mice
(7 animals per
group)
Group 3) 48-h
supplemented with
leucine
Group 4) Control
48-h FTO gene expression was reduced in Leucine added group
Johansson
et al.
41
Experimental 16 mice
(8 mice per
group)
Group 1) leucine-spiked
water
Group 2) Water alone
48-h FTO gene expression was increased in the intervention group
Calorie restriction
Olszewski
et al.36
Experimental 16 mice
(8 animals per
group)
Group 1) High calorie
diet
Group 2) 16-h fasting
16-h FTO gene expression was increased in 48-h fasting group
Fredriksson
et al.
38
Experimental 24 rats
(eight animals
per group)
Group 1) Low calorie diet
Group 2) Food-deprived
Group 2) Normal diet
48-h Expression of the FTO gene is up-regulated during starvation
Glucose
Poritsano
et al.
39
Experimental 610 mice per
group
Group 1) Low calorie diet
And Glucose
administration
Group 2) Normal diet
Group 3) Low calorie diet
48-h FTO gene expression was reduced after low calorie diet and increased after
Glucose administration in the intervention group
S. Doaei et al. / Indian Heart Journal 69 (2017) 277281 279
no changes in hypothalamic FTO expression after a 48-h palatable
sucrose feeding (Table 2).
36
4. Discussion
The present systematic review investigates the potential impact
of dietary components (such as protein, carbohydrate and fat) on
FTO gene expression. Based on this review of 6 intervention
studies, there is some evidence that suggest the possibility that
macronutrients affect hypothalamic FTO expression. Also most of
studies (4 of 6 studies) indicated that higher macronutrients levels
can decrease FTO gene expression (36, 37, 38 and 40) and two
studies reported decrease FTO gene (39 and 41).
There is no clear evidence about the reason of existing
contradiction between short-term and long-term effects of
macronutrients on FTO gene expression. But it may depends on
the wide range of FTO gene roles in hypothalamus.
4350
The recent
studies reported that FTO has a role in macronutrients
metabolism.
4345
For instance, a study by Gulati et al.
45
found
an important role of FTO in matching cellular amino acids levels
with mammalian target of rapamycin complex 1 (mTORC1)
signaling. On the other hand, many studies found that FTO gene
polymorphisms had a critical role in FTO gene expression level and
its effects on obesity.
46,47
Although other studies reported that FTO
gene polymorphisms werent linked with FTO gene expres-
sion.
48,49
The literature currently available is also insufcient to
examine the impact of wide range of polymorphisms on FTO gene
expression.
This review suggests that both the level of calorie and the level
of each macronutrients have a potential to change FTO gene
expression level. Because of the variation in duration of interven-
tion (48-h to 6 weeks), it is not clear what length of intervention is
most effective. Only one study included long-term follow-up data
(more than 48-h intervention),
40
and there is no enough evidence
on the optimal FTO gene expression with regard to healthy weight
management.
The present review emphasize on the possibility that changes in
macronutrients levels affect hypothalamic FTO expression and
thereby affect regulation of appetite and body weight. We need
further investigation of the relationship between macronutrients
and hypothalamic FTO expression in future research.
These type of studies may contribute to determining ways in
which nutrition specialists and researchers can make more
informed decisions about which types of macronutrients and diet
are most suitable in achieving sustainable weight reduction via
impact the level of FTO gene expression. Although it was not found
any clear evidence of an exacteffect of dietary interventions on FTO
gene expression, the use of dietary modications have the
potential to assist researchers in dealing with the obesity epidemic.
Future research should include mediating factors associated with
the impact of dietary intervention on FTO gene expression, and
should also include more long-term follow-up. In addition,
assessment of FTO gene expression related health outcomes, such
as obesity and Diabetes should be included in future research.
Disclosure
The authors report no conicts of interest in this work.
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S. Doaei et al. / Indian Heart Journal 69 (2017) 277281 281
... Interestingly, SNPs of intron 1 of FTO have also been suggested to affect the expression of adjacent genes such as Iroquois homeobox 3 (IRX3), Iroquois homeobox 5 (IRX5), and RPGR-Interacting Protein 1-Like (RPGRIP1L) [22][23][24]. Another possible FTO role in obesity is the regulation of macronutrient intake due to the involvement of FTO expressed in the hypothalamus [25][26][27]. Although the overall impact of FTO gene polymorphisms on BMI and body composition was established, the impact and role of specific SNPs are less clear [12,28]. ...
Article
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Background: Variants in fat mass and the obesity-associated protein (FTO) gene have long been recognized as the most significant genetic predictors of body fat mass and obesity. Nevertheless, despite the overall evidence, there are conflicting reports regarding the correlation between different polymorphisms of the FTO gene and body mass index (BMI). Additionally, it is unclear whether FTO influences metabolic syndrome (MetS) through mechanisms other than BMI’s impact. In this work, we aimed to analyze the impact of the following FTO polymorphisms on the BMI as well as MetS components in a population of young adult men. Methods: The patient group consisted of 279 Polish young adult men aged 28.92 (4.28) recruited for the MAGNETIC trial. The single-nucleotide polymorphisms (SNPs), located in the first intron of the FTO gene, were genotyped, and the results were used to identify “protective” and “risk” haplotypes and diplotypes based on the literature data. Laboratory, as well as anthropometric measurements regarding MetS, were performed. Measured MetS components included those used in the definition in accordance with the current guidelines. Data regarding dietary patterns were also collected, and principal components of the dietary patterns were identified. Results: No statistically significant correlations were identified between the analyzed FTO diplotypes and BMI (p = 0.53) or other MetS components (waist circumference p = 0.55; triglycerides p = 0.72; HDL cholesterol p = 0.33; blood glucose p = 0.20; systolic blood pressure p = 0.06; diastolic blood pressure p = 0.21). Stratification by the level of physical activity or adherence to the dietary patterns also did not result in any statistically significant result. Conclusions: Some studies have shown that FTO SNPs such as rs1421085, rs1121980, rs8050136, rs9939609, and rs9930506 have an impact on the BMI or other MetS components; nevertheless, this was not replicated in this study of Polish young adult males.
... Recent studies examined the interactions between obesity, CRC, and obesity-related genetic factors such as fat mass and obesity-associated protein (FTO) genes [3,14]. The FTO gene is noticeably expressed in the hypothalamus and is associated with the regulation of food intake and energy balance [15]. FTO inhibitors such as Meclofenamic acid (MA), FB23-2, and R2 hydroxyglutarate (R2HG) have been recently investigated as anticancer drugs in many types of cancer [16]. ...
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Background Colorectal cancer (CRC) is one of the most common cancers in the world. Some dietary factors such as fat intake have been identified as the risk factors for CRC. This study aimed to investigate the effect of fat mass and obesity-associated (FTO) gene rs9939609 polymorphism on the association between CRC and different types of dietary fats. Methods This case-control study was performed on 135 CRC cases and 294 healthy controls in Tehran, Iran. Data on demographic factors, anthropometric measurements, physical activity, the intake of different types of dietary fats, and FTO gene rs9939609 polymorphism was collected from all participants. The association between cancer and dietary fat intake in individuals with different FTO genotypes was assessed using different models of logistic regression. Results Oleic acid intake was higher in the case group compared to the control group in both people with TT (7.2±3.46 vs. 5.83±3.06 g/d, P =0.02) and AA/AT genotypes (8.7±6.23 vs. 5.57 ±3.2 g/d, P <0.001). Among carriers of AA/AT genotypes of FTO rs9939609 polymorphism, a positive association was found between CRC and higher intakes of oleic acid (OR=1.12, CI95% 1.03–1.21, P =0.01) and cholesterol (OR=1.01, CI95% 1.00–1.02; P =0.01) after adjusting for age, sex, physical activity, alcohol use, smoking, calorie intake, and body mass index. Conclusion Higher intakes of cholesterol and oleic acid were associated with a higher risk of CRC in FTO-risk allele carriers. The association of CRC and dietary fat may be influenced by the FTO genotype. Further longitudinal studies are warranted to confirm these findings.
... Some studies suggested that the level of calories and the level of macronutrients intake have the potential to change the FTO gene expression level. For instance, one study indicated that increasing glucose administration increased FTO gene expression at 48 h post-intervention [52]. High levels of blood glucose and insulin apply some of their effects through the steady activation of the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway that is involved in cell survival, and eventually, increase the risk of cancer. ...
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Background Dietary components can influence the effects of genetic background in breast cancer (BC). This review study aimed to investigate the effect of dietary components on the expression level of BC-related genes. Methods In this narrative review, Embase, PubMed, PsycInfo, and the Cochrane databases were used to collect the related papers with interactions of BC, genetics, and dietary intake. Appropriate keywords such as BC, gene expression, mutation, nutrient, and diet (alone and together) were applied for data collection. Results The association of BC with some genes including the BC1 gene ( BRCA1 ), the human epidermal growth factor receptor 2 ( HER2 ), and the fat mass and obesity-associated ( FTO ) gene can be affected by dietary components. Moderate B12 supplementation may be protective against BC in people with the inherited mutation of BRCA . The olive oil may have a protective effect against BC through several mechanisms such as suppressing HER-2 expression. Furthermore, high glycemic index foods may increase the risk of BC by the activation of the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway and the up-regulation of FTO gene expression. Conclusion There are interactions between BC, BC-related genes, and dietary intake. Dietary components such as macronutrients, micronutrients, and phytochemicals may regulate the expression level of BC-related genes. Further longitudinal studies are needed to confirm the associations between BC-related genes and diet and to discover the underlying mechanisms.
... The FTO gene is linked to the presence of macronutrients in the body. Doaei et al. (2017) concluded that the FTO gene expression in the hypothalamus is proportional to macronutrient levels. Future research is necessary to evaluate the long-term effects of dietary interventions in this instance. ...
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A new research field is emerging that combines nutrition and genetics at the molecular level, namely nutrigenomics. Several aspects of nutrigenomics are examined in this review, with a particular focus on psychological disorders. The origin of this field in the 20th century and its modern developments have been investigated. Various studies have reported the impact of genetic factors and diet on various chronic disorders, elucidating how the deficiency of several macronutrients results in significant ailments, including diabetes, cancer, cardiovascular disorders, and others. Furthermore, the application of nutrigenomics to diet and its impact on the global disease rate and quality of life have been discussed. The relationship between diet and gene expression can facilitate the classification of diet-gene interactions and the diagnosis of polymorphisms and anomalies. Numerous databases and research tools for the study of nutrigenomics are essential to the medical application of this field. The nutrition-gene interrelationships can be utilized to study brain development, impairment, and diseases, which could be a significant medical breakthrough. It has also been observed that psychological conditions are exacerbated by the interaction between gut microbes and the prevalence of malnutrition. This article focuses on the impact of nutrition on genes involved in various psychological disorders and the potential application of nutrigenomics as a revolutionary treatment method.
... For example, it is suggested that FTO gene levels in the liver are involved in lipid deposition that may lead to NAFLD [48]. Its expression is related to the type and amount of macronutrients [49]. Interestingly, the gene-diet interaction can affect the success of lifestyle interventions in the prevention and treatment of NAFLD. ...
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Background: The type and amount of dietary fats play an important role in fat accumulation in the liver. Sesame oil (SO) is a good source of monounsaturated acids (MUFAs) and polyunsaturated fatty acids (PUFAs). Objective: This trial aimed at examining the effect of SO consumption on the levels of liver enzymes and the severity of fatty liver in women with nonalcoholic fatty liver disease (NAFLD) undergoing a weight loss diet. Methods: This randomized, double-blind, controlled trial was carried out on 60 women with NAFLD. Subjects were randomly assigned to the SO group (n = 30) and sunflower oil (SFO) group (n = 30), each person consuming 30 grams of oil per day for 12 weeks. All the participants received a hypocaloric diet (-500 kcal/day) during the study. Fatty liver grade and liver enzymes were assessed at pre- and postintervention phases. Results: 53 patients completed the study. Significant reductions in body weight, body mass index (BMI), waist circumference (WC), and fatty liver grade were observed in both groups (P < 0.05). Following SO, significant decreases in serum aspartate and alanine aminotransferases (AST and ALT) were observed. After adjusting for confounders, ALT, AST, and fatty liver grade of the SO group were significantly reduced compared to the SFO group (P < 0.05). However, the changes in serum alkaline phosphatase (ALP) were not significant (P > 0.05). Conclusions: The desired effects of weight loss were reinforced by the consumption of SO through improving fatty liver severity and serum ALT and AST levels in NAFLD patients. Moreover, low-calorie diets may lead to favorable outcomes for NAFLD patients through mitigation of obesity and fatty liver grade.
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Background FTO gene is associated with obesity, dietary intake, and the risk of colorectal cancer (CRC). In this study, patients with colorectal cancer were assessed for the interactions between FTO gene polymorphisms and dietary intake. Methods This case–control study was carried out on 450 participants aged 35–70 years including 150 patients with colorectal cancer and 300 healthy controls. Blood samples were collected in order to extract DNA and genotyping of FTO gene for rs9939609 polymorphism. A validated 168-item food frequency questionnaire (FFQ) and the Nutritionist-IV software were used to assess dietary intake. Results In the participants with the TT genotype of FTO rs9939609 polymorphism, CRC risk was significantly associated with higher intake of dietary fat (OR:1.87 CI95%:1.76–1.99, p = 0.04), vitamin B3 (OR:1.20 CI95%:1.08–1.65, p = 0.04), and vitamin C (OR:1.06 CI95%:1.03–1.15, p = 0.04) and lower intake of β-carotene (OR:0.98 CI95%:0.97–0.99, p = 0.03), vitamin E (OR:0.77 CI95%:0.62–0.95, p = 0.02), vitamin B1 (OR:0.15 CI95%:0.04–0.50, p < 0.01), and biotin (OR:0.72 CI95%:0.0.57–0.92, p = 0.01). No significant association was found between CRC and dietary intake in carriers of AA/AT genotypes after adjustments for the confounders. Conclusion CRC risk may be decreased by β-carotene, vitamins E, B1, and biotin only in those without the risk allele of the FTO gene. The association of CRC and diet may be influenced by FTO genotype. Further studies are warranted.
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In this review, we summarize the current state of knowledge on the fat mass and obesity-associated (FTO) gene and its role in obesity. The FTO encoded protein is involved in multiple molecular pathways contributing to obesity as well as other metabolic complexities. This review emphasizes the epigenetic influence on the FTO gene as a new approach in the treatment and management of obesity. Several known substances have a positive effect on reducing FTO expression, depending on the polymorphism of a single nucleotide (SNP) also changes gene expression. Implementing environmental changes could lead to reduced phenotypic manifestation of FTO expression. Treating obesity through FTO gene regulation will have to include various complex signal pathways in which FTO takes part. Identification of FTO gene polymorphisms may be useful for the development of individual obesity management strategies, including the recommendation of taking certain foods and supplements.
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Carcinogenesis is a complicated process and originates from genetic, epigenetic, and environmental factors. Recent studies have reported a potential critical role for the fat mass and obesity-associated (FTO) gene in carcinogenesis through different signaling pathways such as mRNA N6-methyladenosine (m6A) demethylation. The most common internal modification in mammalian mRNA is the m6A RNA methylation that has significant biological functioning through regulation of cancer-related cellular processes. Some environmental factors, like physical activity and dietary intake, may influence signaling pathways engaged in carcinogenesis, through regulating FTO gene expression. In addition, people with FTO gene polymorphisms may be differently influenced by cancer risk factors, for example, FTO risk allele carriers may need a higher intake of nutrients to prevent cancer than others. In order to obtain a deeper viewpoint of the FTO, lifestyle, and cancer-related pathway interactions, this review aims to discuss upstream and downstream pathways associated with the FTO gene and cancer. The present study discusses the possible mechanisms of interaction of the FTO gene with various cancers and provides a comprehensive picture of the lifestyle factors affecting the FTO gene as well as the possible downstream pathways that lead to the effect of the FTO gene on cancer.
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A high-fat diet is believed to be a risk factor for hypertension through inducing obesity. It has been reported that variants of the fat mass and obesity-associated (FTO) and beta-3 adrenergic receptor (B3AR) genes are associated with obesity and blood pressure. The purpose of this study was to investigate the effect of dietary fat on blood pressure with or without the variant of the FTO and B3AR genes. A total of 227 healthy Japanese women aged 18 to 64 years were recruited for measurement of nutrient intake and blood pressure. The single nucleotide polymorphism rs9939609 of the FTO gene and rs4994 of the B3AR gene were genotyped. Spearman’s rank correlation coefficient was applied to investigate the relationship between fat intake and blood pressure. A hierarchical multiple regression analysis was performed to determine whether the genotype interacts with fat intake to affect blood pressure. No significant correlations were found between fat intake and either systolic or diastolic blood pressure. A significant negative correlation was found between fat intake and both blood pressures in the FTO-gene-variant group, but not in the normal-FTO-gene group. In hierarchical multiple regression analysis, the interaction of fat intake and the gene variant showed significance, and the change in coefficient of determination (R²) was significantly increased with increases of the interaction variable. These results indicate that the effect of fat intake on blood pressure may be modified by the variant of the FTO gene such that a high-fat diet intake may be associated with a decrease of systolic and diastolic blood pressure in healthy Japanese women with the FTO variant. Our results did not support the hypothesis that a high-fat diet increases blood pressure. graphical abstract Fullsize Image
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Obesity is influenced by environmental, behavioral, and genetic factors; particularly genes related to the regulation of lipids and addictive behavior. Food craving (FC) is a physiological and behavioral response that triggers the intense desire to ingest food, particularly food with high energy, fat, and/or sweet content. Objective: To evaluate the relationship between the prevalence of FC in obese subjects and blood lipids as well as to determine the transcriptional modulation of CART, DRD2, and FTO. Method: Transverse, comparative, and randomized study including 21 obese participants (BMI, ≥30 kg/m2] and 20 normal weight participants (BMI, ≤25 kg/m2). We determined CART, DRD2, and FTO expressions; evaluated blood lipid levels; and obtained trait scores on the Food Craving Questionnaire-Trait, a multifactorial instrument validated for the Mexican population. Results: The DRD2 expression was significantly increased (p = 0.027) and the CART expression was significantly decreased (p = 0.001) in obese participants compared with normal weight participants. The FTO expression did not show significant differences. Food Craving Questionnaire-Trait showed scores of ≥72 in obese participants. Conclusions: Linear regression model analysis showed that FC is a predictor of atherogenic index (ATH), independently of BMI, and of the gene expression modulation of CART and DRD2.
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Zhang X, Qi Q, Zhang C, Hu FB, Sacks FM, Qi L. FTO genotype and 2-year change in body composition and fat distribution in response to weight-loss diets: the POUNDS LOST trial. Diabetes 2012;61:3005–3011 In the print version of the article listed above, there was an omission of authors and their institutional affiliations. The POUNDS LOST study, on which this project was based, was jointly conducted by the Harvard School of Public Health in Boston, Massachusetts, …
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About one third of adolescents in the USA are overweight and/or obese. Obesity during the adolescent years is associated with many adverse health consequences, including type 2 diabetes, hypertension, hyperlipidemia, and psychosocial problems. Because of substantial advances in technologies and wide acceptance by adolescents, it is now possible to use technology for healthy weight management and prevention of obesity. This systematic review used Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and aimed to evaluate the existing literature reported on the effectiveness of technology-based intervention (web-based, e-learning, and active video games) in preventing obesity in adolescents. The primary aim of this review was to explore if components of specific interventions were associated with a reduction in body mass index. Research articles obtained from CINAHL, Embase, PubMed, PsycInfo, and the Cochrane database from1990 to 2014 were reviewed. A total of 131 published articles were identified, and 14 met the inclusion criteria of a randomized or nonrandomized clinical study with body mass index as primary outcome and/or secondary outcomes of diet/physical activity and/or psychosocial function, tested lifestyle interventions to prevent obesity, used technology, and studied adolescents (aged 12-18 years). The results indicated that six of 14 studies found body mass index and/or body fat decreased at short-term (less than 12 months) follow-up. Six of eleven studies that examined physical activity or physical activity-related outcomes found an improved physical activity outcome (time playing active video games and increase in physical activity time), while five of seven studies which assessed dietary outcomes indicated improvement in dietary behaviors. Five of seven studies suggested an improvement in psychosocial function (reduced depression, improved self-esteem and efficacy, improvement on Behavior Assessment Scale) in adolescents involved in the technology-based intervention. All effective interventions utilized dietary and physical activity strategies as part of intervention components. Because of the variation in duration of intervention (range 10 weeks to 2 years), it is not clear what length of intervention is most effective. Future research should assess the long-term impact of technology-based interventions and evaluate mediators and moderators for weight change in adolescents.
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Salt sensitivity of blood pressure (BP) is an independent risk factor for cardiovascular morbidity. Up to 50% of patients with essential hypertension are salt-sensitive, as manifested by a rise in BP with salt intake. Several genetic variations have been identified as being associated with salt sensitivity. The present study aimed to review the evidence on the effect of gene polymorphisms on the salt sensitivity of BP. We searched in PubMed website from 1990 to 2011, with the use of following keywords: "hypertension, dietary salt, polymorphisms, and blood pressure". The effect of sodium intake on BP differed by genotype at the genes of the renin-angiotensin system, aldosterone synthase, cytochrome p450 3A, epithelial sodium channel genes, genes of sympathetic nervous system, β-3 subunit of G-protein, alpha-adducin, endothelial nitric oxide synthase, Kallikrein-Kinin system. These approaches suggest that these polymorphisms may be potentially useful genetic markers of BP response to dietary salt. There is evidence that genetic predisposition modulates the BP response to diet. Therefore, diet and nutrition can mitigate or enhance the effects of genetic predisposition. Increasing our knowledge of this relationship can lead to individualized treatment and increased understanding of hypertension.
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Genome-wide association studies (GWAS) have reproducibly associated variants within introns of FTO with increased risk for obesity and type 2 diabetes (T2D). Although the molecular mechanisms linking these noncoding variants with obesity are not immediately obvious, subsequent studies in mice demonstrated that FTO expression levels influence body mass and composition phenotypes. However, no direct connection between the obesity-associated variants and FTO expression or function has been made. Here we show that the obesity-associated noncoding sequences within FTO are functionally connected, at megabase distances, with the homeobox gene IRX3. The obesity-associated FTO region directly interacts with the promoters of IRX3 as well as FTO in the human, mouse and zebrafish genomes. Furthermore, long-range enhancers within this region recapitulate aspects of IRX3 expression, suggesting that the obesity-associated interval belongs to the regulatory landscape of IRX3. Consistent with this, obesity-associated single nucleotide polymorphisms are associated with expression of IRX3, but not FTO, in human brains. A direct link between IRX3 expression and regulation of body mass and composition is demonstrated by a reduction in body weight of 25 to 30% in Irx3-deficient mice, primarily through the loss of fat mass and increase in basal metabolic rate with browning of white adipose tissue. Finally, hypothalamic expression of a dominant-negative form of Irx3 reproduces the metabolic phenotypes of Irx3-deficient mice. Our data suggest that IRX3 is a functional long-range target of obesity-associated variants within FTO and represents a novel determinant of body mass and composition.
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