Is fat mass & obesity-associated (FTO) gene master regulator of obesity ?
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ABSTRACT:
SUBMITTER: Mittal B
PROVIDER: S-EPMC4892070 | biostudies-literature | 2016 Mar
REPOSITORIES: biostudies-literature
Publications
Is fat mass & obesity-associated (FTO) gene master regulator of obesity ?
Mittal Balraj B Srivastava Apurva A Srivastava Neena N
The Indian journal of medical research 20160301 3
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Project description: Not available
| S-EPMC5543400 | biostudies-literature
Project description:Common genetic variants of the fat mass and obesity associated (FTO) gene are strongly associated with obesity and type 2 diabetes. FTO is ubiquitously expressed. Earlier studies have focused on the role of hypothalamic FTO in the regulation of metabolism. However, recent studies suggest that expression of hepatic FTO is regulated by metabolic signals, such as nutrients and hormones, and altered FTO levels in the liver affect glucose and lipid metabolism. This review outlines recent findings on hepatic FTO in the regulation of metabolism, with particular focus on hepatic glucose and lipid metabolism. It is proposed that abnormal activity of hepatic signaling pathways involving FTO links metabolic impairments such as obesity, type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). Therefore, a better understanding of these pathways may lead to therapeutic approaches to treat these metabolic diseases by targeting hepatic FTO. The overall goal of this review is to place FTO within the context of hepatic regulation of metabolism.
| S-EPMC6266206 | biostudies-other
Project description:Obesity and osteoporosis are closely correlated genetically. FTO gene has been consistently identified to be associated with obesity phenotypes. A recent study reported that the mice lacking Fto could result in lower bone mineral density (BMD). Thus, we hypothesize that the FTO gene might be also important for osteoporosis phenotypes. To test for such a hypothesis, we performed an association analyses to investigate the relationship between SNPs in FTO and BMD at both hip and spine. A total of 141 SNPs were tested in two independent Chinese populations (818 and 809 unrelated Han subjects, respectively) and a Caucasian population (2,286 unrelated subjects). Combining the two Chinese samples, we identified 6 SNPs in FTO to be significantly associated with hip BMD after multiple testing adjustments, with the combined P values ranged from 4.99 × 10??-1.47 × 10??. These 6 SNPs are all located at the intron 8 of FTO and in high linkage disequilibrium. Each copy of the minor allele of each SNP was associated with increased hip BMD values with the effect size (beta) of ?0.025 and ?0.015 in the Chinese sample 1 and 2, respectively. However, none of these 6 SNPs showed significant association signal in the Caucasian sample, by presenting some extent of ethnic difference. Our findings, together with the prior biological evidence, suggest that the FTO gene might be a new candidate for BMD variation and osteoporosis in Chinese populations.
| S-EPMC3220685 | biostudies-literature
Project description:Obesity has become a major health crisis in the past ∼50 years. The fat mass and obesity-associated (FTO) gene, identified by genome-wide association studies (GWAS), was first reported to be positively associated with obesity in humans. Mice with more copies of the FTO gene were observed to be obese, while loss of the gene in mice was found to protect from obesity. Later, FTO was found to encode an m6A RNA demethylase and has a profound effect on many biological and metabolic processes. In this review, we first summarize recent studies that demonstrate the critical roles and regulatory mechanisms of FTO in obesity and metabolic disease. Second, we discuss the ongoing debates concerning the association between FTO polymorphisms and obesity. Third, since several small molecule drugs and micronutrients have been found to regulate metabolic homeostasis through controlling the expression or activity of FTO, we highlight the broad potential of targeting FTO for obesity treatment. Improving our understanding of FTO and the underlying mechanisms may provide new approaches for treating obesity and metabolic diseases.
| S-EPMC10404889 | biostudies-literature
Project description:Fat mass and obesity-associated gene (FTO) is a member of the Fe (II)- and oxoglutarate-dependent AlkB dioxygenase family and is linked to both obesity and intellectual disability. The role of FTO in neurodevelopment and neurogenesis, however, remains largely unknown. Here we show that FTO is expressed in adult neural stem cells and neurons and displays dynamic expression during postnatal neurodevelopment. The loss of FTO leads to decreased brain size and body weight. We find that FTO deficiency could reduce the proliferation and neuronal differentiation of adult neural stem cells in vivo, which leads to impaired learning and memory. Given the role of FTO as a demethylase of N6-methyladenosine (m6A), we went on to perform genome-wide m6A profiling and observed dynamic m6A modification during postnatal neurodevelopment. The loss of FTO led to the altered expression of several key components of the brain derived neurotrophic factor pathway that were marked by m6A. These results together suggest FTO plays important roles in neurogenesis, as well as in learning and memory.
| S-EPMC6192412 | biostudies-literature
Project description:BackgroundObesity has been shown to increase breast cancer risk. FTO is a novel gene which has been identified through genome wide association studies (GWAS) to be related to obesity. Our objective was to evaluate tissue expression of FTO in breast and the role of FTO SNPs in predicting breast cancer risk.MethodsWe performed a case-control study of 354 breast cancer cases and 364 controls. This study was conducted at Northwestern University. We examined the role of single nucleotide polymorphisms (SNPs) of intron 1 of FTO in breast cancer risk. We genotyped cases and controls for four SNPs: rs7206790, rs8047395, rs9939609 and rs1477196. We also evaluated tissue expression of FTO in normal and malignant breast tissue.ResultsWe found that all SNPs were significantly associated with breast cancer risk with rs1477196 showing the strongest association. We showed that FTO is expressed both in normal and malignant breast tissue. We found that FTO genotypes provided powerful classifiers to predict breast cancer risk and a model with epistatic interactions further improved the prediction accuracy with a receiver operating characteristic (ROC) curves of 0.68.ConclusionIn conclusion we have shown a significant expression of FTO in malignant and normal breast tissue and that FTO SNPs in intron 1 are significantly associated with breast cancer risk. Furthermore, these FTO SNPs are powerful classifiers in predicting breast cancer risk.
| S-EPMC3089782 | biostudies-literature
Project description:Background & objectivesThe fat mass and obesity-associated (FTO) gene is known to be associated with obesity. However, no data are available on the relation between FTO rs9930506 polymorphism and obesity in Polish population. The aim of this study was to evaluate an association between rs9930506 variants of the FTO gene and obesity in Polish adults.MethodsThe study group consisted of 442 adults, aged 33.9 ±12.7 yr, with mean BMI 27.2 ± 5.4 kg/m2. The following variables were determined for each subject: fasting blood glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides. Real-time PCR was used to detect the A/G alleles of the rs9939506 polymorphism in the FTO gene. An association between the rs9930506 polymorphism and obesity was determined using codominant, dominant, and recessive models. The odds ratio (OR) was calculated to determine the risk of obesity associated with this polymorphism.ResultsIt was observed that the presence of FTO rs9939506 G allele was associated with increased risk for obesity and this association was found significant in both recessive (OR = 1.72, P = 0.014) and co-dominant (OR = 1.36, P = 0.031) models of inheritance. The FTO rs9939506 GG homozygotes had a significantly higher BMI than those with other genotypes.Interpretation & conclusionsThis study shows that FTO rs9939506 GG genotype is related to higher BMI and is associated with obesity in Polish adults.
| S-EPMC4892073 | biostudies-literature
Project description:BACKGROUND The distribution of fat mass and obesity-associated gene (FTO) genes rs9939609 and rs1421085 in obese and normal ethnic Mongolians was analyzed to investigate the association of FTO gene polymorphisms with obesity and metabolic syndrome in ethnic Mongolians. MATERIAL AND METHODS The genotypes of FTO genes rs9939609 and rs1421085 in 500 subjects were detected by allele-specific PCR (AS-PCR). General characteristics and clinical biochemical indicators were compared between the obesity group and the control group. The correlation between different genotypes and obesity metabolic index was also analyzed. RESULTS Body mass, body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-hip ratio (WHR), SBP, DBP, FPG, triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) were higher, while HDL-C was lower in the obesity group compared with controls. The frequencies of TT genotype and T allele in the obesity group were higher than those in the control group. The frequencies of these 3 genotypes and allele frequencies of Rs1421085 were comparable between the 2 groups (P>0.05). The risk of obesity in Mongolian individuals carrying rs9939609 AT genotype was 1.312 times higher and the risk in those carrying AA genotype was 1.896 times higher than in individuals with TT genotype. The body weight, BMI, WC, HC, and WHR in individuals with rs9939609 AA and AT genotypes were significantly higher than in those with TT genotype. CONCLUSIONS The AT/AA genotype and allele A of rs9939609 are associated with an increased risk of obesity.
| S-EPMC6251077 | biostudies-literature
Project description:Common variants of human fat mass- and obesity-associated gene Fto have been linked with higher body mass index, but the biological explanation for the link has remained obscure. Recent findings suggest that these variants affect the homeobox protein IRX3. Here we report that FTO has a role in white adipose tissue which modifies its response to high-fat feeding. Wild type and Fto-deficient mice were exposed to standard or high-fat diet for 16 weeks after which metabolism, behavior and white adipose tissue morphology were analyzed together with adipokine levels and relative expression of genes regulating white adipose tissue adipogenesis and Irx3. Our results indicate that Fto deficiency increases the expression of genes related to adipogenesis preventing adipocytes from becoming hypertrophic after high-fat diet. In addition, we report a novel finding of increased Irx3 expression in Fto-deficient mice after high-fat feeding indicating a complex link between FTO, IRX3 and fat metabolism.
| S-EPMC4363842 | biostudies-literature
Project description: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.
| S-EPMC9776650 | biostudies-literature