FTO Gene Research Articles

Down-regulation of the FTO gene in follicular fluid of infertile women with ovarian endometriosis

Objective To evaluate FTO concentrations in follicular fluid (FF) of women with ovarian endometriosis (OE) and controls women without OE undergoing in vitro fertilization-embryo transfer (IVF-ET). Methods FTO concentrations in FF were measured in 74 patients (37 in the control group and 37 in the OE group) by ELISA. We measured the expression of FTO in GCs of 40 patients (19 in the control group and 21 in the OE group) by RT-qPCR. The level of m6A in GCs was measured in 20 patients (10 in the control group and 10 in the OE group) by colorimetry. Results Compared with the control group, FTO concentrations in FF (6.92 ± 0.44 vs. 5.67 ± 0.40 ng/ml) (p <.05) and FTO mRNA level in GCs of OE group were decreased significantly (p <.05), and the level of m6A was increased (0.21 ± 0.01 vs. 0.17 ± 0.03 ng) (p >.05). Conclusions The FTO concentrations in FF of infertility women with OE are decreased, which may be related to the impaired oocyte quality in endometriosis patients.

Rare Variants of Obesity-Associated Genes in Young Adults with Abdominal Obesity.

The increase in the prevalence of overweight, obesity and associated diseases is a serious problem. The aim of the study was to identify rare variants in obesity-associated genes in young adults with abdominal obesity in our population and to analyze information about these variants in other populations. Targeted high-throughput sequencing of obesity-associated genes was performed (203 young adults with an abdominal obesity phenotype). In our study, all of the 203 young adults with abdominal obesity had some rare variant in the genes associated with obesity. The widest range of rare and common variants was presented in ADIPOQ, FTO, GLP1R, GHRL, and INS genes. The use of targeted sequencing and clinical criteria makes it possible to identify carriers of rare clinically significant variants in a wide range of obesity-associated genes and to investigate their influence on phenotypic manifestations of abdominal obesity.

Lack of association of the alpha-ketoglutarate-dependent dioxygenase (FTO) gene polymorphisms with pulmonary tuberculosis risk: a systematic review and meta-analysis.

Our meta-analysis aims to explore the association of two single nucleotide variants; rs9939609 and rs8050136, within the FTO gene with risk of pulmonary tuberculosis (PTB). The association of two single nucleotide variants with PTB in three genetic models was evaluated using pooled odds ratios (ORs) with 95% CIs. No significant association was observed between the rs9939609 polymorphism and PTB when assuming an allelic model (OR: 1.10; 95% CI: 0.85-1.41; P=0.47; I2 = 64.98%), a recessive model (OR: 2.04; 95% CI: 0.87-4.77; P=0.10; I2 = 67.18%), or a dominant model (OR: 0.96; 95% CI: 0.83-1.11; P=0.56; I2 = 27.45%). Likewise, no association was observed between rs8050136 polymorphism and PTB when assuming allelic model (OR: 1.17; 95% CI: 0.87-1.58; P=0.31; I2 = 64.20%) or recessive model (OR: 1.04; 95% CI: 0.32-3.38; P=0.95; I2 = 68.82%) or dominant model (OR: 1.22; 95% CI: 0.87-1.71; P=0.26; I2 = 58.69%). There might be no association between the rs9939609 and rs8050136 variants in the FTO gene, and the risk of PTB.

Exploring the Impact of Insertion/Deletion in FTO and PLIN1 Genes on Morphometric Traits in Sheep.

This study aimed to identify InDels from the FTO and PLIN1 genes and to analyze their association with morphometric traits in Hu sheep (HS), Dupor sheep (DS), and Small Tail Han sheep (STHS). The FTO and PLIN1 genes were genotyped using the insertion/deletion (InDel) method. A one-way ANOVA with SPSS 26.0 software (IBM Corp, Armonk, NY, USA) was used to assess the effect of the InDel FTO and PLIN1 genes on morphometric traits. The results revealed significant associations between certain InDels and the morphometric traits in different breeds of sheep. Specifically, FTO-2 was significantly associated with cannon circumference (CaC) in HS rams and body height (BoH) in HS ewes (p < 0.05). FTO-2 was also significantly associated with chest width (ChW), CaC, head length (HeL), and coccyx length (CoL) in the STHS breed (p < 0.05). FTO-3 showed significant associations with BoH in HS rams and BoH, back height (BaH), ChW, and chest depth (ChD) in HS ewes (p < 0.05). FTO-3 was also significantly associated with ChW in the DS and STHS breeds (p < 0.05). FTO-5 was significantly associated with body weight (BoW) in the DS breed and BoH in the STHS breed (p < 0.05). Furthermore, PLIN1 was significantly related to BoW in the DS breed and was significantly associated with CoL and forehead width (FoW) in the STHS breed (p < 0.05). In conclusion, the study suggested that InDels in the FTO and PLIN1 genes could provide practical information to improve morphometric traits in sheep breeding.

Association of FTO gene variant rs9939609 with polycystic ovary syndrome from Gujarat, India

BackgroundPolycystic ovary syndrome is a multifactorial endocrine disorder impacting women of reproductive age. Variations within the FTO gene have been linked to both obesity and type 2 diabetes mellitus. Given that PCOS is frequently associated with obesity and compromised glucose tolerance, we investigated the prevalence of the rs9939609 variant within the FTO gene among women diagnosed with PCOS and a control group. Our aim is to uncover potential correlations between this genetic variant, metabolic attributes, and endocrine markers within the Gujarat province of India.MethodWe enrolled a total of 114 participants, (62 individuals diagnosed with PCOS and 52 healthy controls). DNA extraction from venous blood was conducted for all participants. The rs9939609 polymorphism was investigated through tetra-primer amplification refractory mutation system-polymerase chain reaction. Furthermore, we performed biochemical assessments to quantify levels of estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), total testosterone, prolactin (PRL), and Dehydroepiandrosterone sulfate (DHEAS). Statistical analyses were carried out utilizing SPSS version 21 (IBM, USA).ResultsThe present study did not reveal any noteworthy association between cases and controls. The frequencies of genotypes and alleles within the cohorts displayed no statistically significant differences (p = 0.25, p = 0.68, and p = 0.78, respectively). The dominant model indicated a modest risk (OR:1.13, 95%CI: 0.55 to 2.38) toward PCOS development. There was a noticeable statistical difference observed in the levels of total testosterone, DHEAS, and BMI between the case and control groups (p < 0.002, p < 0.0002, p < 0.0008). However, no variations in clinical variables were observed among genotypes within the PCOS group.ConclusionThis is the first study to investigate the association of FTO gene polymorphism and PCOS in Gujarati population. Our study findings indicate that the FTO gene variant is not directly linked to the onset of PCOS. However, it appears to exert an influence on metabolic factors such as obesity and insulin resistance. Notably, our results suggest that insulin resistance is more frequently observed among PCOS patients who are obese, as compared to those with non-obese PCOS patients.

Interaction between genetic susceptibility to obesity and food intake on BMI in Finnish school-aged children

Diet modulates the genetic risk of obesity, but the modulation has been rarely studied using genetic risk scores (GRSs) in children. Our objectives were to identify single nucleotide polymorphisms (SNPs) that drive the interaction of specific foods with obesity and combine these into GRSs. Genetic and food frequency data from Finnish Health in Teens study was utilized. In total, 1142 11-year-old subjects were genotyped on the Metabochip array. BMI-GRS with 30 well-known SNPs was computed and the interaction of individual SNPs with food items and their summary dietary scores were examined in relation to age- and sex-specific BMI z-score (BMIz). The whole BMI-GRS interacted with several foods on BMIz. We identified 7–11 SNPs responsible for each interaction and these were combined into food-specific GRS. The most predominant interaction was witnessed for pizza (p < 0.001): the effect on BMIz was b − 0.130 (95% CI − 0.23; − 0.031) in those with low-risk, and 0.153 (95% CI 0.072; 0.234) in high-risk. Corresponding, but weaker interactions were verified for sweets and chocolate, sugary juice drink, and hamburger and hotdog. In total 5 SNPs close to genes NEGR1, SEC16B, TMEM18, GNPDA2, and FTO were shared between these interactions. Our results suggested that children genetically prone to obesity showed a stronger association of unhealthy foods with BMIz than those with lower genetic susceptibility. Shared SNPs of the interactions suggest common differences in metabolic gene-diet interactions, which warrants further investigation.

FTO gene variants (rs9939609, rs8050136 and rs17817449) and type 2 diabetes mellitus risk: A Meta-Analysis

Background and aimsThere is tremendous increase in type 2 diabetes mellitus (T2DM) worldwide. The impact of FTO gene polymorphisms on the risk of T2DM is not yet clear because of the controversial results of studies. This meta-analysis aimed to better clarify the association between three FTO gene polymorphisms SNPs (rs9939609, rs8050136 and rs17817449) and T2DM in a larger combined population worldwide. Material and methodsA comprehensive search on the PubMed, Science Direct, and Web of Science databases was conducted to identify investigations in relationship between different FTO gene polymorphisms (rs9939609, rs8050136 and rs17817449) and T2DM globally. Published papers from January 2007 to May 2023 were collected. Inclusion criteria are limited to human case-control studies published in English and peer-reviewed, which provided data on the genotype distributions of FTO gene polymorphisms and T2DM risk. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to express the results of the meta-analysis. Potential sources of bias and heterogeneity using Egger's regression analysis were also assessed. ResultsOf 234695 identified articles, forty-eight studies were selected including 36,051 patients with T2DM and 51,266 control subjects. Overall, we found a significant increased risk of T2DM susceptibility and rs9939609 FTO gene polymorphism in the Allele contrast (A vs. T: OR = 1,30, 95% CI = 1.14; 1.48, P < 0,05, I2 = 0,94), Recessive model (AA vs. AT + TT: OR = 1,54, 95% CI = 1.19; 2.00, P < 0,05, I2 = 0,94), Dominant model (AA + AT vs. TT: OR = 1,26, 95% CI = 1.10; 1.45, P < 0,05, I2 = 0,89), homozygote model (AA vs. TT: OR = 1,60, 95% CI = 1.26; 2.03, P < 0,05, I2 = 0,90), and heterozygote model (AA vs. AT: OR = 1,43, 95% CI = 1.09; 1.88, P = 0,008, I2 = 0,93). we also found a significantly increased risk of T2DM susceptibility and rs8050136 FTO gene polymorphism under all models. For rs17817449 we did not find any association between with T2DM. ConclusionThe present meta-analysis confirms that rs9939609 and rs8050136 in the FTO gene are significantly associated with T2DM, while rs17817449 does not show any association.

Longitudinal effects of FTO gene polymorphism on body composition, cardiorespiratory fitness, physical activity, inflammatory markers, and cardiovascular risk in children and adolescents. "The UP & DOWN study".

The role of polymorphism rs9939609 of the FTO gene has been related with fat mass and cardiovascular risk in adults, but it remains unclear in children and adolescents. Hence, the main aim of this study was to determine the FTO polymorphism effects on body composition, cardiorespiratory fitness (CRF), physical activity (PA), inflammatory markers, and cardiovascular risk both in cross-sectional analysis and after two-years of follow-up in children and adolescents. A total of 2129 participants were included in this study. The rs9939609 polymorphism was genotyped. Body composition measurements, CRF, and moderate-to-vigorous PA (MVPA) were determined at baseline and after two-year of follow-up. Moreover, plasma leptin and adiponectin were also determined as inflammatory markers. Furthermore, an index of cardiovascular disease risk factors (CVDRF-I) was calculated. Codominant (TT vs. TA vs. AA) and dominant (AA+AT vs. TT) models were applied for statistical analysis. The results showed a main effect of the FTO genotype on body composition measures in both first and third year (p < 0.05), with lower adiposity in TT compared with AA or AA+AT group. These differences were maintained after accounting for pubertal maturity, sex, age, VO2 max, and MVPA. Moreover, lower leptin level was observed in TT compared to AA+AT group in the third year. An interaction in Gene*Time*Sex was found in height and neck circumference in dominant model (p = 0.047; p = 0.020, respectively). No differences were found in CRF, MVPA nor CVDRF-I between groups. Hence, homozygous TT allele could be a protective factor against weight gain from early childhood.

NEFA Dynamics in Adults With Severe Obesity and Insulin Resistance: No Coupling to the rs9939609 FTO Risk Allele.

The FTO gene is highly expressed in adipose tissues; however, whether nonesterified fatty acids (NEFA) dynamics are impacted by FTO has not been rigorously tested for in a uniformly obese study population comprising both sexes. To test for associations of the rs9939609 FTO risk allele with NEFA suppression. We investigated 97 subjects with severe obesity but without diabetes, having genotype TT (n = 32), AT (n = 31), or AA (n = 34) in a cross-sectional observation study. NEFA suppression was assessed from a low-dose hyperinsulinemic euglycemic clamp with glucose-tracer as well as from the response to a standardized meal. Insulin sensitivity was assessed by hepatic and total insulin sensitivity measurements in the clamp and by the Matsuda index during the meal. Variables of possible importance for NEFA dynamics were primarily assessed by linear regression. No genotype associations with fasting or suppressed NEFA were found, whether in the clamp or meal situation (P > .7 for all comparisons). Independent of genotype, higher fasting concentrations of NEFA and larger NEFA suppression were found in female compared with male subjects. Fasting NEFA or degree of suppression were not associated with total fat mass or body mass index. The respiratory quotient was negatively associated with NEFA suppression. In a gender-mixed adult population of obese individuals, an FTO obesity-risk allele did not affect fasting NEFA nor suppression thereof. These negative results on NEFA dynamics appear strengthened by the documentation of gender influence and associations with parameters reflective of insulin resistance.

Effect of Sedentary behaviors on the Interaction Between the FTO Gene and Adiposity Levels in Chilean Adults - Results from the GENADIO Study

The Fat-mass and obesity-associated-gene (FTO gene) and sedentary behavior time are associated with obesity. However, whether sedentary behavior time can modify the genetic predisposition to obesity in the Chilean population is unknown. Therefore, this study investigated the association between sedentary behavior, adiposity markers, and the FTO gene. This cross-sectional study included 409 participants from the Genes, Environment, Diabetes, and Obesity (GENADIO) study. Adiposity markers studied included body weight, body mass index (BMI), waist circumference (WC), and fat mass. Sedentary behaviors were measured using accelerometers. Using multiple regression, we evaluated the interaction between sedentary behaviors and the FTO gene (rs9939609) on adiposity markers. Sedentary behaviors and the FTO genotype were positively associated with higher body weight, BMI, WC, and fat mass. However, the association between time of sedentary behavior and adiposity markers was higher in carriers of the risk variant for the FTO gene. For each hour of increment in sedentary behaviors, body weight increases by 1.36 kg ([95% CI: 0.27; 2.46], p = 0.015) and 2.95 kg ([95%CI: 1.24; 4.65], p = 0.001) in non-risk carriers (TT) versus risk carriers (AA), respectively. We observed similar results for WC, BMI, and body fat, but the interaction was significant only for WC. The association between sedentary behaviors and adiposity markers, especially body weight and WC, is higher in individuals who carry the risk variant of the FTO gene.

Cool executive functions and their association with body mass & fatness and the FTO gene in school-aged children

The FTO gene rs9936909 polymorphism is one of the well-documented single nucleotide polymorphisms in the context of increased risk of obesity, including in children. Few studies have tested the association of the FTO gene with cognitive functions. Deficits of “cool” executive functions (EFs) are considered a potential risk factor for excessive weight. The aims of our study were to investigate whether cool EFs are associated with the Body Mass Index, the Fat Mass Index and the risk of excess body mass and overfatness in neurotypically school-aged children, and whether the FTO gene polymorphism is involved in development of this possible association. The sample consisted of 553 children aged 6–12 years old. A body composition analysis, a neuropsychological assessment of EFs, and FTO polymorphism genotyping were performed in the children studied. The study found a significant association of an interference effect in theStroop Color-Word Interference Task and the risk of excessive body fatness, but not excessive body mass. There were no explicit associations between the FTO genotype and EFs deficits. Environmental factors, and particularly low maternal education, appeared to be the strongest contributors to the increased risk of obesity.

Molecular Mechanism of m6A Methylation Modification Genes METTL3 and FTO in Regulating Heat Stress in Sheep.

Heat stress is an important environmental factor affecting livestock production worldwide. Primary hepatocytes and preadipocytes derived from Hu sheep were used to establish a heat stress model. Quantitative reverse transcriptase-PCR (qRT-PCR) analysis showed that heat induction significantly increased the expression levels of heat stress protein (HSP) genes and the N6-methyladenosine (m6A) methylation modification genes: methyltransferase-like protein 3 (METTL3), methyltransferase-like protein 14 (METTL14), and fat mass and obesity associated protein (FTO). Heat stress simultaneously promoted cell apoptosis. Transcriptome sequencing identified 3980 upregulated genes and 2420 downregulated genes related to heat stress. A pathway enrichment analysis of these genes revealed significant enrichment in fatty acid biosynthesis, degradation, and the PI3K-Akt and peroxisome proliferator-activated receptor (PPAR) signaling pathways. Overexpression of METTL3 in primary hepatocytes led to significant downregulation of HSP60, HSP70, and HSP110, and significantly increased mRNA m6A methylation; FTO interference generated the opposite results. Primary adipocytes showed similar results. Transcriptome analysis of cells under METTL3 (or FTO) inference and overexpression revealed differentially expressed genes enriched in the mitogen-activated protein kinase (MAPK) signaling pathways, as well as the PI3K-Akt and Ras signaling pathways. We speculate that METTL3 may increase the level of m6A methylation to inhibit fat deposition and/or inhibit the expression of HSP genes to enhance the body's resistance to heat stress, while the FTO gene generated the opposite molecular mechanism. This study provides a scientific basis and theoretical support for sheep feeding and management practices during heat stress.

The effects of FTO gene rs9939609 polymorphism on the association between colorectal cancer and dietary intake.

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. 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. 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. 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.

The rs1421085 variant within FTO promotes brown fat thermogenesis.

One lead genetic risk signal of obesity-the rs1421085 T>C variant within the FTO gene-is reported to be functional in vitro but lacks evidence at an organism level. Here we recapitulate the homologous human variant in mice with global and brown adipocyte-specific variant knock-in and reveal that mice carrying the C-allele show increased brown fat thermogenic capacity and resistance to high-fat diet-induced adiposity, whereas the obesity-related phenotypic changes are blunted at thermoneutrality. Both in vivo and in vitro data reveal that the C-allele in brown adipocytes enhances the transcription of the Fto gene, which is associated with stronger chromatin looping linking the enhancer region and Fto promoter. Moreover, FTO knockdown or inhibition effectively eliminates the increased thermogenic ability of brown adipocytes carrying the C-allele. Taken together, these findings identify rs1421085 T>C as a functional variant promoting brown fat thermogenesis.

Associations of polymorphisms of some genes with cardiometabolic risk factors in adolescents from Novosibirsk

Aim of the study was to investigate the association of polymorphisms of some genes with overweight and certain anthropometric and biochemical parameters in a population sample of adolescents in Novosibirsk. Material and methods. In 2019, a population-based screening of a representative sample of adolescents (609 people) was carried out in Novosibirsk. All children and their parents signed an informed consent for the examination. The study was approved by the local Ethics Committee of the Research Institute of Internal and Preventive Medicine – Branch of the Institute of Cytology and Genetics of SB RAS. During the examination, a questionnaire was filled out, anthropometric measurements were carried out, blood sampling was carried out, followed by a biochemical study. 157 people (75 boys (47.8 %), 82 girls (52.2 %)) were selected for molecular genetic analysis using tables of random numbers. The weight status of adolescents was assessed using the IOTF (International Obesity Task Force) criteria. The subsequent analysis compared 2 groups: 1st group included teenagers with weight deficiency and normal body weight), the 2nd – with overweight, obesity and extreme obesity). Results. In the general group, differences in carriers of different genotypes of the rs9939609 FTO gene were found in the level of low-density lipoprotein cholesterol (LDL-C) (p = 0,024). The girls with the AA rs9939609 genotype had the greatest average thickness of the skin fold in the middle third of the right shoulder. Differences were found in carriers of different genotypes rs7903146 of TCF7L2 gene in the average fasting plasma glucose (FPG) level (p = 0,021). The average thickness of the skin fold in the middle third of the right shoulder was greater in girls carrying the CC genotype compared with carriers of the CT and TT genotypes (p = 0,041). In separate subgroups, in carriers of different genotypes of rs10811661 CDKN2AB gene were found differences in high-density lipoprotein cholesterol, FPN, and waist circumference, in nucleotide sequence variant (NSV) rs2237892 KCNQ1 gene carriers – in triglyceride, FPG, LDL-C and total cholesterol concentration, in rs1111875 HHEX gene carriers – in total cholesterol, LDL-C level, waist and hip circumference, thickness of the skin fold under the scapula, diastolic blood pressure. Conclusions. Associations of the studied NSV (rs9939609, rs7903146, rs10811661, rs2237892, rs1111875) were found in the group as a whole and in separate subgroups (with division by body mass index, gender), with anthropometric and biochemical parameters, such as total cholesterol, triglyceride, LDL-C, FPN content, diastolic blood pressure, waist and hip circumferences, thickness of the skin fold under the scapula and in the middle third of the right shoulder. There were no statistically significant differences in the frequencies of studied NVS genotypes and alleles between the 1st and 2nd groups.

ESR1 and FTO genetic variants: impact on body weight reduction following bariatric surgery

Background Variation in reduction of body weight after bariatric surgery has been observed. Genetics may have a role in the varying outcomes among obese patients. Aim of this research work was to examine the effect of genetic variants within the Fat Mass and Obesity-Related gene (FTO) (rs9939609) and Estrogen Receptor Alpha gene (ESR1) (rs712221) on body weight reduction and blood glucose control in obese individuals, six months following laparoscopic sleeve gastrectomy (LSG). Patients and methods Ninety obese individuals with BMI ≥35 kg/m2 undergoing LSG were recruited and followed up after 6 months. Genotyping for FTO gene (rs9939609) and ESR1 gene (rs712221) variants was done using Real-Time PCR (TaqMan probes). Results FTO (rs9939609) genotype AA was found to be associated with more obesity before operation (P value 0.005) and lead to successful surgery and weight loss (P value 0.023, OR 0.080, 95%CI 0.009–0.702). Patients with risk allele A had more weight loss and BMI reduction after operation compared to patients with non-risk allele T (P value &lt;0.001). ESR1 (rs712221) genotype TT was found to be associated with more reduction of body weight six months after surgery when compared to genotypes TA and AA (P value 0.001). Carriers of the allele T of the ESR1 (rs712221) had more reduction of HbA1c after operation compared to patients with allele A (P value &lt;0.001). Conclusion The single nucleotide variants; rs9939609 of FTO and rs712221 of ESR1 may be considered potential predictors of body weight reduction and/or blood sugar control following bariatric surgery for obese individuals.

FTO Gene Polymorphisms and Their Roles in Acromegaly.

The major causes of both morbidity and mortality in patients with acromegaly are cardiovascular diseases (CVDs). The polymorphisms of the fat mass and obesity-associated gene (FTO) are associated with obesity, as well as with an increased risk of CVDs. The aim of the study was to determine the relationship of risk alleles of four FTO gene polymorphisms with selected parameters of lipid and glucose metabolism as well as with IGF-1 and GH levels in the group of patients with acromegaly compared to the control group. The study group consisted of 104 patients with acromegaly and 64 healthy subjects constituting the control group. In the whole acromegaly group, the data reveal that the homozygous for risk allele carriers (rs1421085, rs9930506, rs9939609) as well as carriers of only one risk allele have lower IGF-1 concentrations. In the well-controlled acromegaly group, the homozygous for three risk allele carriers of FTO gene polymorphisms have lower HDL cholesterol concentration (rs1121980, rs1421085, rs993609). In the cured acromegaly group, homozygous risk allele carriers rs9930506 tend to have higher levels of total cholesterol and LDL cholesterol. These associations are not observed in the control group. Conclusion: there is an association between FTO gene polymorphisms and the metabolism of lipids, suggesting that the FTO gene may be associated with higher CVD risk in patients with acromegaly. In addition, there is an association between FTO gene polymorphisms and IGF-1, implying that FTO gene may influence/modify IGF-1 synthesis. Further investigation on a larger scale is required to provide more precise evidence.

Association of the DNA Methylation of Obesity-Related Genes with the Dietary Nutrient Intake in Children.

The occurrence of obesity stems from both genetic and external influences. Despite thorough research and attempts to address it through various means such as dietary changes, physical activity, education, and medications, a lasting solution to this widespread problem remains elusive. Nutrients play a crucial role in various cellular processes, including the regulation of gene expression. One of the mechanisms by which nutrients can affect gene expression is through DNA methylation. This modification can alter the accessibility of DNA to transcription factors and other regulatory proteins, thereby influencing gene expression. Nutrients such as folate and vitamin B12 are involved in the one-carbon metabolism pathway, which provides the methyl groups necessary for DNA methylation. Studies have shown that the inadequate intake of these nutrients can lead to alterations in DNA methylation patterns. For this study, we aim to understand the differences in the association of the dietary intake between normal weight and overweight/obese children and between European American and African American children with the DNA methylation of the three genes NRF1, FTO, and LEPR. The research discovered a significant association between the nutritional intake of 6-10-years-old children, particularly the methyl donors present in their diet, and the methylation of the NRF1, FTO, and LEPR genes. Additionally, the study emphasizes the significance of considering health inequalities, particularly family income and maternal education, when investigating the epigenetic impact of methyl donors in diet and gene methylation.

Human abdominal subcutaneous-derived active beige adipocytes carrying FTO rs1421085 obesity-risk alleles exert lower thermogenic capacity.

Introduction: White adipocytes store lipids, have a large lipid droplet and few mitochondria. Brown and beige adipocytes, which produce heat, are characterized by high expression of uncoupling protein (UCP) 1, multilocular lipid droplets, and large amounts of mitochondria. The rs1421085 T-to-C single-nucleotide polymorphism (SNP) of the human FTO gene interrupts a conserved motif for ARID5B repressor, resulting in adipocyte type shift from beige to white. Methods: We obtained abdominal subcutaneous adipose tissue from donors carrying FTO rs1421085 TT (risk-free) or CC (obesity-risk) genotypes, isolated and differentiated their preadipocytes into beige adipocytes (driven by the PPARγ agonist rosiglitazone for 14 days), and activated them with dibutyryl-cAMP for 4 hours. Then, either the same culture conditions were applied for additional 14 days (active beige adipocytes) or it was replaced by a white differentiation medium (inactive beige adipocytes). White adipocytes were differentiated by their medium for 28 days. Results and Discussion: RNA-sequencing was performed to investigate the gene expression pattern of adipocytes carrying different FTO alleles and found that active beige adipocytes had higher brown adipocyte content and browning capacity compared to white or inactive beige ones when the cells were obtained from risk-free TT but not from obesity-risk CC genotype carriers. Active beige adipocytes carrying FTO CC had lower thermogenic gene (e.g., UCP1, PM20D1, CIDEA) expression and thermogenesis measured by proton leak respiration as compared to TT carriers. In addition, active beige adipocytes with CC alleles exerted lower expression of ASC-1 neutral amino acid transporter (encoded by SLC7A10) and less consumption of Ala, Ser, Cys, and Gly as compared to risk-free carriers. We did not observe any influence of the FTO rs1421085 SNP on white and inactive beige adipocytes highlighting its exclusive and critical effect when adipocytes were activated for thermogenesis.

Association of the Gene FTO Single Nucleotide Polymorphism, rs9939609 with Type 2 Diabetes Mellitus in Pakistani Cohort

To date, inconclusive data is available about the insight of the FTO gene variant with type 2 diabetes mellitus. T2DM is a chronic disease and a rising problem worldwide. Its complications lead to an increase in the burden of mortality specifically in lower and medium-income countries. Genome-wide association studies have spotted many genetic loci that are related to T2DM and validate the complicated polygenic traits. Many variants of different genes including FTO are associated with T2DM hence, this study was designed to inspect and unfold obscure data in South Asians. The main objective of present study is to identify the relation of FTO intronic variant rs9939609 with T2DM in Karachi-based Sindhi population of Pakistan. Total recruited individuals were grouped as diabetic cases and controls. Out of the total recruited subjects, genotyping was done on 152 samples using T-ARMS PCR however, demographic and clinical data were recorded of all individuals. The results showed that the frequency of variant genotypes in the diabetic case group was 11 % for AA, 45 % for AT and 44 % for TT though, the frequency of the lethal allele (T) was 34 %. These outcomes concluded, rare T allele frequency is higher among diabetic cases as compared to controls and provides the contribution from the Pakistani population to support the previous controversial findings. This study concluded FTO gene-single nucleotide polymorphism, rs9939609 is associated with T2DM but still, it is a growing need to do further studies on T2DM susceptible genes with different polymorphisms to recognize targets in the field of pharmacogenomics for clinical implementation.