FTO Rs9939609 Research Articles

Prevalence, associated factors, and gene polymorphisms of obesity in Tibetan adults in Qinghai, China

ObjectivesTo explore the prevalence and associated factors of obesity in Tibetan adults in Qinghai, China, and to determine the association between the FTO (rs1121980 and rs17817449) and MC4R gene (rs17782313 and rs12970134) polymorphisms with obesity.MethodsA cross-sectional survey was conducted in 2015 in Qinghai to selected Tibetan adults aged 20 to 80 years. Prevalence of obesity (BMI ≥ 28 kg/m2) and overweight (BMI 24 ~ 27.9 kg/m2) were evaluated. Multivariable logistic models were used to determine the associated factors. Pair-matched subjects of obesity cases and normal-weight controls were selected for the gene polymorphism analyses. Conditional logistic models were used to assess the association between gene polymorphisms with obesity. Additive and multiplicative gene-environment interactions were tested.ResultsA total of 1741 Tibetan adults were enrolled. The age- and sex- standardized prevalence of obesity and overweight was 18.09% and 31.71%, respectively. Male sex, older age, heavy level of leisure-time exercise, current smoke, and heavy level of occupational physical activity were associated with both obesity and overweight. MC4R gene polymorphisms were associated with obesity in Tibetan adults. No significant gene-environment interaction was detected.ConclusionThe prevalence of obesity and overweight in Tibetan adults was high. Both environmental and genetic factors contributed to the obesity prevalent.

Associations Between rs9939609 FTO Polymorphism With Nutrient and Food Intake and Adherence to Dietary Patterns in an Urban Argentinian Population

BackgroundThe A allele of rs9939609 polymorphism at the FTO gene has been consistently associated with higher body mass index in different populations, but conflicting results have been found regarding its contribution to food intake variability. ObjectiveThis study aimed to investigate the association between this genetic variant and nutrient and food intake in an urban Argentinian population. DesignA cross-sectional, analytic investigation was performed between October 2018 and February 2020. Participants/settingsAdults of both sexes residing in La Plata, Argentina, were recruited through social networks (Instagram and Facebook). Of 179 eligible adults, a total of 173 adults were included in the final analyses. Outcome measuresNutrient and food group intake data were obtained by an interview-administered food frequency questionnaire. Height and weight were measured, and genotypes were obtained by real-time polymerase chain reaction. Statistical analysesThe per-allele effect on nutrient and food group intake was assessed by general linear models, adjusting for age, sex, educational level, total energy intake, and body mass index. Dietary patterns were derived by principal component analysis. The association of the A allele with adherence to each dietary pattern was also evaluated by the general linear model. ResultsThe frequency of the risk allele was 27%. A-carriers showed a higher total fat (1.88 [0.55, 3.21] % of total energy intake), saturated fatty acids (0.82 [0.25–1.39] % of total energy intake), and monounsaturated fatty acids (0.66 [0.08, 1.24] % of total energy intake), and a lower carbohydrate (−1.99 [−3.48, −0.50] % of total energy intake) intake than TT homozygous. A-carriers also reported a higher “milk and yogurt” (1.08 [0.24, 1.91] % of total energy intake), “animal fats” (1.09 [0.14–2.03] % of total energy intake), and fat-rich ultraprocessed foods (2.10 [0.52, 3.67] % of total energy intake) intake in comparison with TT homozygous. Furthermore, A-carriers showed higher adherence to the Western dietary pattern. ConclusionThe A allele contributed to nutrient and food intake variability in the studied population and was associated with the consumption of saturated fatty acids–enriched foods.

TCF7L2 and FTO Polymorphisms Are Associated with Type 2 Diabetes Mellitus Risk in Kuwait

Objective: Despite the high prevalence of type 2 diabetes mellitus (T2DM) and obesity in the region, reports are limited on genetic risk factors associated with T2DM risk in Kuwait. Our aim was to investigate the association of reported FTO and TCF7L2 T2DM genetic risk variants in Kuwaiti T2DM patients. Subjects and Methods: FTO rs9939609 and TCF7L2 rs7903146 variants were genotyped in 203 T2DM patients and 162 healthy controls. Data analysis included Fisher’s exact test, χ2 test, and linear and logistic regression analyses. Results: FTO rs9939609 (AA) and TCF7L2 rs7903146 (TT) genotypes associated with T2DM risk among Kuwaitis (p = 0.0016 and p < 0.0001; respectively). Both variants had the strongest association with T2DM risk in an autosomal recessive inheritance model (FTO rs9939609A: odds ratio (OR) 2.136, 95% confidence interval (CI): 1.21–3.67, p = 0.0075; TCF7L2 rs7903146T: OR 3.283, 95% CI: 1.92–5.76, p < 0.0001). Moreover, rs7903146T associated with risk of peripheral neuropathy (β = 0.735, 95% CI: 0.514–0.96, p < 0.001) and risk of myocardial infarction (β = 0.36, 95% CI: 0.024–0.7, p = 0.036) in T2DM patients. Conclusion: The increased susceptibility of Kuwaitis to T2DM is influenced by the same common genetic factors found in other T2DM populations. Further investigations of other T2DM genetic risk factors in Kuwait should refine and further support the clinical utility of a genetic risk score in predicting T2DM risk in a high-risk population such as Kuwait.

Variability of the SNP rs9939609 in the FTO Gene and Ancestry in Latin American Populations

Introduction: Obesity is a complex condition influenced by genetic and environmental factors. The FTO gene has been associated with obesity through several single nucleotide polymorphisms (SNPs), particularly rs9939609, related to higher body mass index (BMI) and risk of obesity. FTO variants influence the regulation of appetite and energy metabolism by affecting RNA methylation and the expression of key genes in adipogenesis.Objective: To investigate the association between the FTO rs9939609 SNP and genetic ancestry proportions in Latin American populations.Methods: Genotypes for rs9939609 were obtained using VcfTools and the 1000 Genomes Project database. Samples from Latin America were selected, covering four mixed populations: Colombians (n=94), Mexicans (n=64), Peruvians (n=85) and Puerto Ricans (n=104), totaling 347 individuals. To estimate genetic ancestry proportions, 446 SNPs from a panel of ancestry informative markers (AIMs) were used.Results: Individuals with the AA genotype of SNP rs9939609 have a higher proportion of Native American ancestry and a lower proportion of European ancestry compared to TT and AT genotypes. The variability in the proportions of ancestry according to the genotype of the SNP rs9939609 suggests a possible genetic stratification in the Latin American populations studied.Conclusions: These findings highlight the importance of considering ancestral composition in genetic studies related to obesity. More research is needed to understand how gene-environment interactions contribute to obesity in various populations, which could lead to more effective and targeted intervention strategies

Genetic Polymorphisms Associated with Metabolic Syndrome in North Africa: Systematic Review and Meta-Analysis

Background: Metabolic syndrome (MetS) is a multifactorial disorder characterized by the aggregation of various metabolic disorders, including obesity, hyperglycemia, hypertriglyceridemia, hypoHDLemia and hypertension. In addition to environmental influences, genetic factors can play a major role in the development of MetS. Objective: The present bibliographic review aims to examine the contribution of candidate gene polymorphisms to MetS susceptibility in North African populations. Methods: A systematic review search was conducted to identify pertinent articles published on Embase, PubMed, and Web of Science from their inception to August 2, 2023 to obtain all reported genetic data related to MetS in North African populations. Results: According to the literature search strategy, 785 articles were initially obtained from the cited databases, and 15 more papers were found utilizing other sources. Following the filtering procedure, 25 papers totalising 3925 cases and 4431 controls were included, from which only 13 were eligible for meta-analysis. The meta-analysis results suggest that the genetic cumulative risk of developing MetS was substantially influenced by four polymorphisms, including APOA5 (rs3135506 and rs662799), APOC3 (rs5128), and FTO (rs9939609), while the vaspin polymorphism (rs2236242) was reported to play a protective role from MetS. Furthermore, no significant association was observed between rs1169288, rs2464196, and rs735396 polymorphisms at HNF1A gene and MetS development. A narrative synthesis of association studies revealed that a multitude of candidate genes is associated with MetS components. In all included studies, 14 polymorphisms were linked to obesity, and 13 polymorphisms were associated with hyperglycemia. The association of hypertension with polymorphisms represents the lowest number, with only seven polymorphisms associated with this MetS component. In the other hand, studies about MetS in North Africa considering the genetic association of candidate genes with dyslipidemia component represents the highest number with 20 polymorphisms in approximately 14 genes. Conclusion: The present meta-analysis suggests that four polymorphisms, namely rs3135506 and rs662799 at APOA5 gene, rs5128 at APOC3 and rs9939609 at FTO, contributed significantly to the MetS risk susceptibility, via their association with some MetS components as dyslipidemia, hyperglycemia, obesity, and hypertension. Nevertheless, we can state that genetic association and genetic susceptibility studies to MetS in North African populations are still lacking, requiring additional well-designed epidemiogenetic studies.

From the reward network to whole-brain metrics: structural connectivity in adolescents and young adults according to body mass index and genetic risk of obesity.

Obesity is a multifactorial condition. Genetic variants, such as the fat mass and obesity related gene (FTO) polymorphism, may increase the vulnerability of developing obesity by disrupting dopamine signaling within the reward network. Yet, the association of obesity, genetic risk of obesity, and structural connectivity of the reward network in adolescents and young adults remains unexplored. We investigate, in adolescents and young adults, the structural connectivity differences in the reward network and at the whole-brain level according to body mass index (BMI) and the FTO rs9939609 polymorphism. One hundred thirty-two adolescents and young adults (age range: [10, 21] years, BMI z-score range: [-1.76, 2.69]) were included. Genetic risk of obesity was determined by the presence of the FTO A allele. Whole-brain and reward network structural connectivity were analyzed using graph metrics. Hierarchical linear regression was applied to test the association between BMI-z, genetic risk of obesity, and structural connectivity. Higher BMI-z was associated with higher (B = 0.76, 95% CI = [0.30, 1.21], P = 0.0015) and lower (B = -0.003, 95% CI = [-0.006, -0.00005], P = 0.048) connectivity strength for fractional anisotropy at the whole-brain level and of the reward network, respectively. The FTO polymorphism was not associated with structural connectivity nor with BMI-z. We provide evidence that, in healthy adolescents and young adults, higher BMI-z is associated with higher connectivity at the whole-brain level and lower connectivity of the reward network. We did not find the FTO polymorphism to correlate with structural connectivity. Future longitudinal studies with larger sample sizes are needed to assess how genetic determinants of obesity change brain structural connectivity and behavior.

Minor alleles of FTO rs9939609 and rs17817449 polymorphisms confer a higher risk of type 2 diabetes mellitus and dyslipidemia, but not coronary artery disease in a Chinese Han population.

Relationships of the polymorphisms in fat mass and obesity-associated gene (FTO) and peroxisome proliferator-activated receptor delta gene (PPARD) with metabolic-related diseases remain to be clarified. One thousand three hundred and eighty-one subjects were enrolled. Metabolic-related diseases including obesity, dyslipidemia, hyperhomocysteinemia, hyperuricemia, hypertension, type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) were defined based on diagnostic criteria. FTO rs9939609 and rs17817449, and PPARD rs2016520 and rs2267668 polymorphisms were genotyped by using polymerase chain reaction-restricted fragment length polymorphism method. Patients with T2DM or dyslipidemia had a higher frequency of AA, AT or AA + AT genotypes as well as A allele of FTO rs9939609 polymorphism than those free of T2DM or dyslipidemia (P ≤ 0.04 for all). Patients with T2DM or dyslipidemia had a higher frequency of GG, GT or GG + GT genotypes as well as G allele of FTO rs17817449 polymorphism than those free of T2DM or dyslipidemia (P ≤ 0.03 for all). Multivariate logistic regression analyses showed that FTO rs9939609 and rs17817449 polymorphisms were independently associated with T2DM as well as dyslipidemia after adjustment for age, sex, smoking and other metabolic diseases. FTO rs9939609 and rs17817449 polymorphisms were not associated with obesity, hyperhomocysteinemia, hyperuricemia, hypertension and CAD. Obese or T2DM carriers of the AA or AT genotype of the FTO rs9939609 polymorphism had a higher prevalence of dyslipidemia compared to non-obese or non-T2DM carriers of the AA or AT genotype (P = 0.03 for both). Among the carriers of GG or GT genotype of the FTO rs17817449 polymorphism, the prevalence of dyslipidemia in obese patients was higher than that in non-obese subjects (P < 0.01). PPARD rs2016520 and rs2267668 polymorphisms were not correlated with any of the metabolic-related diseases in the study population. Minor alleles of FTO rs9939609 and rs17817449 polymorphisms confer a higher risk of T2DM and dyslipidemia, and the risk is further increased among obese individuals. PPARD rs2016520 and rs2267668 polymorphisms are not associated with metabolic-related diseases.

Fat mass and obesity-associated gene (FTO) rs9939609 (A/T) polymorphism and food preference in obese people with low-calorie intake and non-obese individuals with high-calorie intake

The purpose of this study was to assess the connection between FTO rs9939609 (A/T) polymorphism and food preference. The study included 77 participants, 36 of whom were obese and had a low-calorie intake, and 41 non-obese participants with a high-calorie intake. Using a food frequency questionnaire (FFQ), the researchers calculated sweet and fatty food propensity scores. Genomic DNA was extracted from a peripheral blood sample from all participants, and FTO rs9939609 (A/T) polymorphism was assessed using standard methods. The study found no significant differences between the two groups in terms of sweet food preference (15.64 ± 10.53 in obese groups vs. 14.72 ± 7.95 in the non-obese group, p = 0.711) and fatty food preference (16.81 ± 8.84 vs. 17.27 ± 8.75; p = 0.833). Additionally, the study did not find any significant correlation between FTO rs9939609 (A/T) polymorphism and sweet and fatty food preferences in the fully adjusted models (p > 0.05). Therefore, the results of this study do not support the hypothesis of different food preferences.

Type 2 diabetes linked FTO gene variant rs8050136 is significantly associated with gravidity in gestational diabetes in a sample of Bangladeshi women: Meta-analysis and case-control study.

Gestational diabetes mellitus (GDM) is a growing public health concern that has not been extensively studied. Numerous studies have indicated that a variant (rs8050136) of the fat mass-associated gene, FTO, is associated with both GDM and Type 2 diabetes mellitus(T2DM). We conducted a meta-analysis on the association between the FTO single nucleotide polymorphism (SNP) rs8050136 and T2DM, followed by a case-control study on the association of the said SNP and GDM in a sample of Bangladeshi women. A total of 25 studies were selected after exploring various databases and search engines, which were assessed using the Newcastle-Ottawa Scale (NOS). The MetaGenyo web tool was used to conduct this meta-analysis. A case-control study was performed on 218 GDM patients and 284 controls to observe any association between FTO rs8050136 and GDM. Genotyping was performed using the tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS) method, and statistical analyses were performed using various statistical softwares. In the meta-analysis 26231 cases and 43839 controls were examined. Pooled association analyses revealed a statistically significant relationship between the FTO rs8050136 polymorphism and an elevated risk of T2DM under all genetic models (P<0.05). In the case-control study, synergistic analyses of the SNP and gravida with GDM revealed a significant (P<0.01) association with an increase in odds by 1.6 to 2.4 folds in multigravida and decrease in odds by 2 folds in primigravida. A positive family history of diabetes and the minor allele of this SNP collectively increased the risk of developing GDM by many-fold (1.8 to 2.7 folds). However, after accounting for family history of diabetes and gravidity, analyses showed no significant association with GDM. Our meta-analysis revealed a significant association between SNP rs8050136 of FTO with T2DM, and this variant was substantially associated with an increased risk of GDM in a sample of Bangladeshi multigravida women.

Interaction of common variants of FTO gene and Dietary Inflammatory Index on obesity measures: Tehran Lipid and Glucose Study

BackgroundThis study aimed to examine the interaction of Dietary Inflammatory Index (DII) and fat mass and obesity-associated gene (FTO) single-nucleotide polymorphisms (SNPs) on change in obesity measures.MethodsA total of 4480...

Higher atherogenic risk in schoolchildren is associated with MTMR9 rs2293855 gene polymorphism and genetic score.

Childhood dyslipidaemia is associated with the occurrence of cardiovascular diseases in adulthood, so evaluating whether an individual has a genetic predisposition to this pathology is of great importance for early action of prevention and treatment. This study aimed to evaluate the association between the FTO (rs9939609), MC4R (rs17782313) and MTMR9 (rs2293855) polymorphisms, the obesity-related genetic risk score and atherogenic risk in Brazilian children. This is a cross-sectional study conducted in 544 children aged 4-9 years in the city of Viçosa, Minas Gerais state, Brazil. The single nucleotide polymorphisms rs9939609, rs17782313 and rs2293855, were identified by the system TaqMan SNP genotyping and the obesity-related genetic risk score was determined. The lipid profile (serum total cholesterol [TC], high density lipoprotein [HDL] cholesterol, low density lipoprotein [LDL] cholesterol, triglycerides) was analysed and the atherogenic indices (Castelli I and II indices), atherogenic coefficient (AC), lipoprotein combined index (LCI) and plasma atherogenic index (PAI) were calculated. A semi-structured questionnaire was applied, obtaining data on the sociodemographic, economic and lifestyle characteristics of the children. Weight and height measurements were performed in all children, and body composition was evaluated by Dual-Energy X-ray Absorptiometry (DXA). 55.5% of the sample had dyslipidaemia, while 28.5% of the sample had at least one polymorphism and 2.2% had three polymorphisms. Children with the AG/AA genotypes in the rs2293855 polymorphism had lower HDL cholesterol levels and higher TC/HDL cholesterol, LDL/HDL cholesterol ratios and AC. Those with one or more polymorphisms (rs9939609, rs17782313 and rs2293855) in the genetic risk score had lower HDL cholesterol levels and higher TC/HDL cholesterol ratios, AC, LCI and PAI. In conclusion, the risk allele of the rs2293855 polymorphism and a higher obesity-related genetic risk score were positively associated with higher atherogenic risk in Brazilian children.

Sequence gene variants in PPARGC1A rs8192678, PPARG2 rs1801282, FTO rs9939609, LEP rs7799039, LEPR rs1137101 and nonalcoholic fatty liver disease

Objective: to evaluate the association of sequence variants PPARGC1A rs8192678, PPARG2 rs1801282, FTO rs9939609, LEP rs7799039, LEPR rs1137101 with non-alcoholic fatty liver disease (nAFLD) at young adults in Russian population. Material and methods. The case-control study included 100 patients divided into two groups: group 1 (cases) — with nAFLD (n=50); group 2 (controls) without nAFLD (n=50). All subjects underwent a standard ultrasound examination of the liver and ultrasound shear wave elastography (Aixplorer, France) with an assessment of the severity of liver steatosis and fibrosis. Results. We found two sequence variants associated with an increased risk of nAFLD in women: rs9939609 and rs7799039: A/A rs9939609 genotype (OR 5,33; 95% Cl 1,14-24,90; p=0,041) and G/G genotype rs7799039 (OR 7,5; 95% Cl 1,04-54,12; p=0,026). Conclusion. The A/A genotype ofthe rs9939609 gene in young women in the Russian population increased the chance of having nAFLD by 5 times, the G/G genotype ofthe rs7799039 gene increased the chance of having nAFLD by 7.5 times.

A study protocol for a pilot randomized controlled trial to evaluate the effectiveness of a gene-based nutrition and lifestyle recommendation for weight management among adults: the MyGeneMyDiet® study.

Managing nutrition and lifestyle practices, nutrition phenotypes, and the genome forms the foundation of precision nutrition. Precision nutrition focuses on metabolic variability among individuals, and one approach to achieving its goals is to integrate gene-based nutrition and lifestyle recommendations in nutrition practice. However, scientific evidence proving the effectiveness of such recommendations is limited. This study will examine whether providing nutrition and lifestyle recommendations based on individual genotype can lead to better weight loss, along with reduction in body mass index (BMI), waist circumference, and body fat percentage among overweight and obese adults. A parallel group, single-blind, randomized controlled trial will be conducted. Sixty-two overweight/obese individuals aged 19-59 years old will be recruited. Participants will be randomly allocated to either the intervention (n = 31) or the control arm (n = 31). Participants in the intervention group will receive the MyGeneMyDiet® Recommendation for Weight Management, a gene-based nutrition and lifestyle recommendation that was developed based on existing evidence of the effects of FTO rs9939609 on body weight, BMI, and physical activity; UCP1 rs1800592 on calorie intake; and TCF7L2 rs7903146 on dietary fat intake. Participants in the control group will receive the standard recommendations for weight management. The primary outcomes will be the differences in weight, BMI, waist circumference, and body fat percentage between arms in both the active phase (6 months) and inactive phase (last 6 months) of the trial. Participants in both arms will be evaluated at baseline and in months 3, 6, 9, and 12. To the best of our knowledge, this will be the first gene-based intervention that will adopt a phase of intensive nutrition counseling, followed by a simulation of a free-living state to determine adherence to a gene-based recommendation. This study will contribute to the future implementation of precision nutrition interventions by providing evidence on the effectiveness of a gene-based nutrition and lifestyle recommendation for weight loss. clinicaltrials.gov, identifier [NCT05098899].

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.

The contribution of FTO rs9939609 and RETN rs1862513 polymorphisms in predisposing resettled indigenous (Orang Asli) Temiar to metabolic syndrome

PurposeMetabolic syndrome (MetS) is characterized by visceral obesity, elevated blood pressure and fasting blood glucose, increased triglycerides, and lower high-density lipoprotein cholesterol. MetS related with intricate gene-environment interactions. FTO and RETN variants were linked to the occurrence of MetS, but inconsistent results were reported. Therefore, this study was conducted to evaluate the potential role of FTO rs9939609 and RETN rs1862513 polymorphisms and their susceptibility risk to MetS among resettled indigenous or Orang Asli (OA) of Temiar subtribe under resettlement scheme by the Malaysia government.MethodsA cross sectional study was performed involving 123 Temiar volunteers located in Gua Musang, Kelantan. MetS was identified using modified NCEP-ATP III. DNA extraction was done using peripheral blood. Polymerase Chain Reaction–Restriction Fragment Length Polymorphism (PCR–RFLP) was employed to genotype FTO rs9939609 and RETN rs1862513 polymorphisms. Susceptibility risk of the polymorphisms (FTO rs9939609 and RETN rs1862513) with MetS was determined by binary logistic regression analysis and odds ratios (ORs).ResultsFTO rs9939609 and RETN rs1862513 were associated with risk of MetS susceptibility among the Temiar subtribe with estimated OR 19.9 (P < 0.001) and 20.7 (P = 0.006) for heterozygous (T/A) and homozygous (A/A) genotype at FTO rs9939609 locus, respectively; OR 222.5 (P < 0.001) and 26.2 (P = 0.005) for heterozygous (C/G) and homozygous (G/G) genotype at RETN rs1862513 locus, respectively.ConclusionThe genetic polymorphisms of FTO rs9939609 and RETN rs1862513 were associated with the risk of MetS among the Temiar subtribe. The findings contribute toward the fundamental prevention plan to decrease the probability of MetS development.

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.

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.

Heightened sensitivity to high-calorie foods in children at risk for obesity: insights from behavior, neuroimaging, and genetics.

Pediatric obesity is a major public health concern. Genetic susceptibility and increased availability of energy-dense food are known risk factors for obesity. However, the extent to which these factors jointly bias behavior and neural circuitry towards increased adiposity in children remains unclear. While undergoing fMRI, 108 children (ages 5-11y) performed a food-specific go/no-go task. Participants were instructed to either respond ("go") or inhibit responding ("no-go") to images of food or toys. Half of the runs depicted high-calorie foods (e.g., pizza) whereas the other half depicted low-calorie foods (e.g., salad). Children were also genotyped for a DNA polymorphism associated with energy intake and obesity (FTO rs9939609) to examine the influence of obesity risk on behavioral and brain responses to food. Participants demonstrated differences in behavioral sensitivity to high- and low-calorie food images depending on task demands. Participants were slower but more accurate at detecting high- (relative to low-) calorie foods when responding to a neutral stimulus (i.e., toys) and worse at detecting toys when responding to high-calorie foods. Inhibition failures were accompanied by salience network activity (anterior insula, dorsal anterior cingulate cortex), which was driven by false alarms to food images. Children at a greater genetic risk for obesity (dose-dependent model of the FTO genotype) demonstrated pronounced brain and behavioral relationships such that genetic risk was associated with heightened sensitivity to high-calorie food images and increased anterior insula activity. These findings suggest that high-calorie foods may be particularly salient to children at risk for developing eating habits that promote obesity.

Impact of the FTO Gene Variation on Appetite and Fat Oxidation in Young Adults

The FTO rs9939609 gene, which presents three polymorphisms (AA, AT, and TT), has been associated with the development of obesity through an increased fat accumulation; however, the associations of the gene with other physiological mechanisms, such as appetite or fat oxidation, are still unclear. Therefore, this study aims to evaluate the influence of the FTO rs9939609 gene on different obesity-related factors in young adults. The FTO rs9939609 polymorphism was genotyped in 73 participants (28 women, 22.27 ± 3.70 years). Obesity-related factors included dietary assessment, physical activity expenditure, body composition, appetite sensation, resting metabolic rate, maximal fat oxidation during exercise (MFO), and cardiorespiratory fitness. Our results showed that TT allele participants expressed higher values of hunger (p = 0.049) and appetite (p = 0.043) after exercising compared to the AT allele group. Moreover, the TT allele group showed significantly higher values of MFO (p = 0.031) compared to the AT group, regardless of sex and body mass index. Thus, our results suggest that the FTO rs9939609 gene has an influence on appetite, hunger, and fat oxidation during exercise, with TT allele participants showing significantly higher values compared to the AT allele group. These findings may have practical applications for weight loss and exercise programs.

Association Study of BDNF, SLC6A4, and FTO Genetic Variants with Schizophrenia Spectrum Disorders.

Schizophrenia spectrum disorders (patients with a diagnosis of schizophrenia, schizotypal, and delusional disorders: F20-F29 according to International Classification of Diseases 10th revision (ICD-10)) are considered highly heritable heterogeneous psychiatric conditions. Their pathophysiology is multifactorial with involved dysregulated serotonergic neurotransmission and synaptic plasticity. The present study aimed to evaluate the association of SLC6A4 (5-HTTLPR), FTO (rs9939609), and BDNF (rs6265, rs962369) polymorphisms with schizophrenia spectrum disorders in Slovak patients. We analyzed the genotypes of 150 patients with schizophrenia, schizotypal, and delusional disorders and compared them with genotypes from 178 healthy volunteers. We have found a marginally protective effect of LS + SS genotypes of 5-HTTLPR variant of the serotonin transporter SLC6A4 gene against the development of schizophrenia spectrum disorders, but the result failed to remain significant after Bonferroni correction. Similarly, we have not proven any significant association between other selected genetic variants and schizophrenia and related disorders. Studies including a higher number of subjects are warranted to reliably confirm the presence or absence of the studied associations.