Fat Mass And Obesity-associated Gene Expression Research Articles

<i>Artocarpus Communis</i> Seed Regulates P53, IRS, HsD17β2, FTO, and CYP11a Genes in Polycystic Ovarian Syndrome Rats

Polycystic ovarian syndrome (PCOS) is a prevalent endocrine illness that affects 5-10% of reproductive women globally. It is a multifaceted hormonal disorder characterized by the involvement of numerous molecular mechanisms that contribute to its development. This study investigates the effect of <em>Artocarpus communis </em>seed on the hormonal imbalance and P53, IRS, HsD17β2, FTO, and CYP11a genes expression in the ovaries of letrozole-induced polycystic ovarian syndrome rats. To induce PCOS in 30 female Wistar rats, letrozole was administered at a dosage of 1 mg/kg. For 12 days, <em>Artocarpus communis </em>seed aqueous extract (100 and 250 mg/kg body weight) and Clomiphene citrate (1 mg/kg body weight), a standard medication, were given. ELISA assessed luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol levels. The levels of P53, IRS, HsD17β2, FTO, and CYP11a gene expression in the ovaries were assessed. The aqueous extract reduced LH and increased FSH levels in Letrozole-induced PCOS rats. Additionally, seed aqueous extract (250 mg/kg bw) regulated the expression of P53, type 2 17-HSD (17-HSD), fat mass and obesity-associated (FTO), 11a-hydroxylase/17,20-desmolase (CYP11a), and insulin receptor substrate (IRS) genes in the ovaries of PCOS rats. Therefore, <em>Artocarpus communis</em> seed might have multifaceted effects on molecular pathways associated with PCOS, potentially normalizing androgen metabolism, hormonal imbalance, and ovarian function.

Effects of dietary supplementation with algae, sunflower oil, or soybean oil, and age on fat content, fatty acid profile and the expression of related genes in rabbits

>Abstract The aim of this study was determine the effect of different dietary supplements (algae, sunflower oil, or soybean oil) and age (12 and 18 weeks) on the fat content, fatty acid (FA) profile, and expression of the fat mass and obesity associated (FTO) and fatty acid binding protein 4 (FABP4) genes in rabbit muscle. Rabbits (n = 160) were randomly divided into four groups. The control group (C) received non-supplemented pellets, while in the other groups the pellet contained 1% algae (A), 3% sunflower oil (OS), or 3% soybean (SO) oil. Soybean and sunflower oil (3%) in the diet increased the linoleic acid (LA) content in meat of 12-week-old rabbits. The use of algae (1%) in the diet increased the n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) compared with the vegetable oil and control groups, and decreased the n-6/n-3 ratio. The effect of the diet on FTO and FABP4 gene expression depended on the age of the rabbits. In older animals (18 weeks of age) the expression of these genes was highest in the group with 1% algae. Furthermore, the FA profile and FTO and FABP4 gene expression were affected by the age of rabbits, but not by sex. The results showed that diet is an important tool to modulate the FA profile in rabbit meat by changing the expression of fat metabolism–related genes.

FTO gene expression in diet-induced obesity is downregulated by Solanum fruit supplementation.

The Fat Mass and Obesity-associated (FTO) gene has been shown to play an important role in developing obesity, manifesting in traits such as increased body mass index, increased waist-to-hip ratio, and the distribution of adipose tissues, which increases the susceptibility to various metabolic syndromes. In this study, we evaluated the impact of fruit-based diets of Solanum melongena (SMF) and Solanum aethiopicum fruits (SAF) on the FTO gene expression levels in a high-fat diet (HFD)-induced obese animals. Our results showed that the mRNA level of the FTO gene was downregulated in the hypothalamus, and white and brown adipose tissue following three and six weeks of treatment with SMF- and SAF-based diets in the HFD-induced obese animals. Additionally, the Solanum fruit supplementation exhibited a curative effect on obesity-associated abrasions on the white adipose tissue (WAT), hypothalamus, and liver. Our findings collectively suggest the anti-obesity potential of SMF and SAF via the downregulation of the FTO gene.

Expression features of the ovine FTO gene and association between FTO polymorphism and tail fat deposition related-traits in Hu sheep

Fat mass and obesity associated (FTO) gene is a famous dominant predictor of obesity, and plays pivotal roles in the regulating fatty acid transport and fat metabolism. In the current study, the quantitative real-time PCR (qRT-PCR), DNA-pooled sequencing and KAspar assay were performed to detect the expression features of FTO and the polymorphisms of FTO associated with the tail fat weight related-traits of Hu sheep. The results indicated that the expression of FTO gene is widely expressed in the tissues tested, and the expression level of FTO in tail fat tissue was evidently higher compared with that in the other tissues. In addition, FTO showed the highest expression level in tail fat tissue at three months. The expression of FTO mRNA was lower in the large-tail fat group compared with that in the small-tail fat group in 6 months old. Subsequently, the polymorphism loci g. 23704451C > A detected in the FTO gene was confirmed to be significantly related to the tail length and the weight of tail fat. These results suggested that the polymorphism might be regarded as novel molecular marker for the breeding of small tail sheep.

Fat mass and obesity-associated gene expression and disease severity in type 2 diabetes mellitus

Obesity and visceral adiposity are major risk factors for type 2 diabetes mellitus (T2DM). The fat mass and obesity-associated (FTO) gene is associated with increased risk of obesity and T2DM. The aim of this work was to study the association between FTO gene expression and serum FTO protein level with disease severity in T2DM patients. Patients and methodsOne hundred T2DM patients were divided into two equal groups according to diabetes control and complications and fifty healthy controls were included in this study. FTO messenger ribonucleic acid (mRNA) expression level was analyzed by Real time polymerase chain reaction (PCR) technique and serum level of FTO protein was measured by ELISA. ResultsFTO gene expression and FTO protein levels were increased in the two T2DM groups compared to the control group with significant further increases in patients with severe disease. FTO gene expression and FTO protein levels were positively correlated with obesity, insulin resistance and blood glucose indices as well as the presence of diabetic complications. Regression analyses showed that FTO gene expression and FTO protein levels were risk factors for T2DM severity. ConclusionsIncreased FTO gene expression and its serum protein levels are associated with increased T2DM severity.

Fat mass- and obesity-associated (FTO) gene promoted myoblast differentiation through the focal adhesion pathway in chicken

The action of FTO on myoblasts proliferation and differentiation and molecular mechanism underlying it were investigated by transfecting with FTO lentiviral overexpression vector and gene expression profile sequencing. Compared with the control group, myoblasts with FTO transfection was significantly enhanced proliferation; the expression of MYOG and MYOD mRNA was significantly increased. In cells transfected with FTO, 129 differentially expressed genes were determined compared with control group, with 104 up-regulated and 25 down-regulated genes. Twelve pathways (Phagosome, Focal adhesion, Adrenergic signaling in cardiomyocytes, Endocytosis, Cardiac muscle contraction, Toll-like receptor, Ribosome, Tight junction, Regulation of actin cytoskeleton, Cytokine-cytokine receptor interaction, Adrenergic signaling in cardiomyocytes and MAPK) were significantly enriched. Eight genes known to be directly or indirectly related to skeletal muscle development (LAMA5, SPP1, CAV3, RASGRF1, FAK, PDGFB, PDGFRα, and RAC2) were enriched in the focal adhesion and expressed differentially. Altogether, these data suggested that FTO stimulated differentiation of myoblasts through regulation of eight genes enriched in the focal adhesion.

Dietary Carbohydrate Promotes Cell Survival in Cancer Via the Up-Regulation of Fat Mass and Obesity-Associated Gene Expression Level.

Cancer cells are mainly dependent on glycolysis for their growth and survival. Dietary carbohydrates play a critical role in the growth and proliferation of cancer and a low-carbohydrate diet may help slow down the growth of tumours. However, the exact mechanisms behind this effect are unclear. This review study aimed to investigate the effect of fat mass and obesity-associated (FTO) gene in the association between dietary carbohydrates and cancer. This study was carried out using keywords such as polymorphism and/or cancer and/or dietary carbohydrate and/or FTO gene. PubMed and Science Direct databases were used to collect all related articles published from 1990 to 2018.Recent studies showed that the level of FTO gene expression in cancer cells is dramatically increased and may play a role in the growth of these cells through the regulation of the cellular metabolic pathways, including the phosphoinositide 3-kinases/protein kinaseB (PI3K/AKT) signaling pathway. Dietary carbohydrate may influence the FTO gene expression by eliminating the inhibitory effect of adenosine monophosphate-activated protein kinase (AMPK) on the FTO gene expression. This review summarised what has been recently discovered about the effects of dietary carbohydrate on cancer cells and tried to determine the mediating role of the FTO gene in these effects.

Interactions between macro-nutrients’ intake, FTO and IRX3 gene expression, and FTO genotype in obese and overweight male adolescents

ABSTRACT This study is the first to identify the effects of FTO genotype on the interactions between the level of macro-nutrients intake and the expression level of fat mass and obesity associated (FTO) and homeobox transcription factor iriquois-3 (IRX3) genes This longitudinal study was carried out on 84 overweight and obese adolescent boys in Tehran, Iran. The rs9930506 SNP in FTO was genotyped at baseline and the level of FTO and IRX3 expression in PBMCs and macro-nutrients’ intake were assessed at baseline and after 18 weeks of the intervention. The results identified that the higher carbohydrates intake significantly up-regulated the FTO gene (P = 0.001) and down-regulated the IRX3 gene (P = 0.01). Protein intake up-regulated the FTO gene (P = 0.001). In carriers of GG genotype of FTO gene, the amount of dietary carbohydrate had a positive association with FTO gene expression (p = 0.001, and p = 0.04, respectively). In AA/AG carriers, dietary protein was positively associated with FTO gene expression (p = 0.001) and dietary carbohydrate was negatively associated with IRX3 gene expression (P = 0.04). Therefore, dietary carbohydrateseems to be associated with FTO and IRX3 genes expression. These associations are influenced by FTO genotype.

The Beneficial Effects of Early Short‐Term Exercise in the Offspring of Obese Mothers are Accompanied by Alterations in the Hypothalamic Gene Expression of Appetite Regulators and FTO (Fat Mass and Obesity Associated) Gene

Maternal overnutrition is implicated in the development of adult metabolic disease, and has been shown to alter the expression of genes involved in energy homeostasis. In the present study, we aimed to test whether a short period of voluntary exercise, followed by a sedentary period, would regulate hypothalamic markers involved in appetite. Adult female Sprague-Dawley rats were fed either normal chow or high-fat diet (HFD) ad lib. for 5 weeks, mated and continued on their assigned diet during gestation/lactation. At weaning males, were separated into chow or HFD groups; half were exercised (running wheels), whereas the remainder were sedentary. At week 10, wheels were removed and rats remained sedentary for 5 weeks, prior to tissue collection. Maternal obesity increased offspring adiposity at 15 weeks and this was exacerbated by postnatal HFD (P < 0.05). Body weight and fat mass were reduced in offspring of obese mothers if they exercised, and this was maintained even after 5 weeks without exercise. At 15 weeks, fasting plasma insulin, leptin and triglyceride concentrations were significantly reduced by exercise in offspring of lean and obese mothers consuming chow, with little benefit in those consuming HFD. Hypothalamic mRNA expression of pro-opiomelanocortin was increased by exercise but only in offspring of lean mothers. Exercise reduced hypothalamic FTO (fat mass and obesity associated) mRNA in offspring of lean dams regardless of diet. A short period of exercise early in life had lasting beneficial effects on body weight, adiposity and hormone profile of male offspring from obese and lean dams, despite being followed by a period of inactivity. The effects of exercise on hypothalamic appetite regulators were more marked in offspring of lean dams.

The expression of FTO in human adipose tissue is influenced by fat depot, adiposity, and insulin sensitivity

The fat mass and obesity associated (FTO) gene is related to obesity, but the regulation of FTO expression in adipose tissue is not fully understood. We investigated FTO expression in paired subcutaneous and omental adipose tissues (SAT and OAT) from healthy women undergoing gynecological surgeries, and its relation with adiposity and insulin sensitivity. FTO expression in SAT of type 2 diabetic patients treated or not with Rosiglitazone was also compared. Both the mRNA and protein levels of FTO were higher in OAT from women than in SAT. Only OAT FTO protein levels negatively correlated with BMI and body fat mass, whereas SAT FTO mRNA levels were negatively correlated with subcutaneous fat deposition. In addition, SAT FTO mRNA and protein levels were increased in insulin resistant women (high HOMA) compared to insulin sensitive women (low HOMA), whereas OAT FTO expression was not different between these two subgroups. Interestingly, FTO mRNA levels were increased in SAT of type 2 diabetic patients, and treatment of diabetics with Rosiglitazone improved insulin sensitivity and reduced SAT FTO mRNA levels. Lastly, FTO expression was transiently increased in the early phase of 3T3-L1 cell differentiation, which coincides with the induction of PPARγ2 expression. However, partial reduction of FTO did not impact PPARγ2 expression and adipocyte differentiation. Therefore, FTO gene expression is higher in OAT than in SAT in lean to moderately obese women. OAT FTO expression is associated with adiposity, whereas SAT FTO expression is associated with insulin sensitivity. These associations are independent of an effect of FTO on adipocyte differentiation.

Comment on: Jowett et al. (2010) Genetic Variation at the FTO Locus Influences RBL2 Gene Expression. Diabetes;59:726–732

Jowett et al. (1) have examined the association of single nucleotide polymorphism (SNP) rs8050136 in intron 1 of the FTO (fat mass– and obesity-associated) gene with levels of transcripts up to 5 Mb in either direction of this SNP in lymphocytes from 1,240 individuals. This is an important study because it has been a matter of debate through which gene the obesity-associated SNPs in intron 1 of the FTO gene affect body weight regulation. The authors did not find an association of these SNPs with FTO gene expression but found a strong association with transcript levels of the RBL2 (retinoblastoma-like 2) gene located 270 kb upstream of FTO. …

Anti-inflammatory Profile of FTO Gene Expression in Adipose Tissues From Morbidly Obese Women

Background: The fat mass and obesity associated (FTO) gene has been found to contribute to the risk of obesity in humans, but the function and regulation of FTO mRNA expression in adipose tissues remain to be clarified. Our aims were to assess the FTO gene expression in subcutaneous and visceral adipose tissues from morbidly obese women and its relation with obesity, insulin resistance indices, and most importantly, to obesity-related inflammatory markers. Methods: Paired subcutaneous and visceral fat were excised from 33 morbidly obese women and 12 control women who underwent bariatric surgery by laparoscopic gastric by-pass and elective surgery respectively. Adipose tissue mRNA expression was determined by real time RT-PCR. Results: FTO mRNA expression in visceral adipose tissue (VAT) was significantly higher than in subcutaneous adipose tissue (SAT) from obese but not control patients. SAT FTO expression was reduced in obese women compared to control subjects. It correlated negatively with BMI and insulin resistance indices. FTO expression in SAT was positively related to both circulating and mRNA levels of adiponectin, to adiponectin receptor and to PPAR-Δexpression, but negatively with IL-6 gene expression and with circulating levels of leptin. FTO in VAT was also positively correlated with adiponectin, adiponectin receptor and PPAR-Δ mRNA expression. Conclusion: FTO expression in subcutaneous adipose tissue negatively correlates with obesity and insulin resistance. On the other hand, FTO presents a positive association with the expression of adiponectin, an anti-inflammatory adipokine, and with PPAR-Δ in both adipose tissues. Taken together, our results suggest that FTO is associated with an anti-inflammatory behaviour in morbid obesity.

Fat Mass–and Obesity-Associated (FTO) Gene Variant Is Associated With Obesity

OBJECTIVE—To examine the longitudinal association of fat mass–and obesity-associated (FTO) variant with obesity, circulating adipokine levels, and FTO expression in various materials from human and mouse.RESEARCH DESIGN AND METHODS—We genotyped rs9939609 in 2,287 men and 3,520 women from two prospective cohorts. Plasma adiponectin and leptin were measured in a subset of diabetic men (n = 854) and women (n = 987). Expression of FTO was tested in adipocytes from db/db mice and mouse macrophages.RESULTS—We observed a trend toward decreasing associations between rs9939609 and BMI at older age (≥65 years) in men, whereas the associations were constant across different age groups in women. In addition, the single nucleotide polymorphism (SNP) rs9939609 was associated with lower plasma adiponectin (log[e]− means, 1.82 ± 0.04, 1.73 ± 0.03, and 1.68 ± 0.05 for TT, TA, and AA genotypes, respectively; P for trend = 0.02) and leptin (log[e]− means, 3.56 ± 0.04, 3.63 ± 0.04, and 3.70 ± 0.06; P for trend = 0.06) in diabetic women. Adjustment for BMI attenuated the associations. FTO gene was universally expressed in human and mice tissues, including adipocytes. In an ancillary study of adipocytes from db/db mice, FTO expression was ∼50% lower than in those from wild-type mice.CONCLUSIONS—The association between FTO SNP rs9939609 and obesity risk may decline at older age. The variant affects circulating adiponectin and leptin levels through the changes in BMI. In addition, the expression of FTO gene was reduced in adipocytes from db/db mice.