Subcutaneous fat mass is associated with genetic risk scores related to proinflammatory cytokine signaling and interact with physical activity in middle-aged obese adults

Abstract

Background and aimsSubcutaneous fat mass is negatively correlated with atherogenic risk factors, but its putative benefits remain controversial. We hypothesized that genetic variants that influence subcutaneous fat mass would modulate lipid and glucose metabolism and have interactions with lifestyles in Korean middle-aged adults with high visceral fat.Materials and methodsSubcutaneous fat mass was categorized by dividing the average of subscapular skin-fold thickness by BMI and its cutoff point was 1.2. Waist circumferences were used for representing visceral fat mass with Asian cutoff points. GWAS of subjects aged 40–65 years with high visceral fat (n = 3303) were conducted and the best gene-gene interactions from the genetic variants related to subcutaneous fat were selected and explored using the generalized multifactor dimensionality reduction. Genetic risk scores (GRS) were calculated by weighted GRS that was divided into low, medium and high groups.ResultsSubjects with high subcutaneous fat did not have dyslipidemia compared with those with low subcutaneous fat, although both subject groups had similar amounts of total fat. The best model to influence subcutaneous fat included IL17A_rs4711998, ADCY2_rs326149, ESRRG_rs4846514, CYFIP2_rs733730, TCF7L2_rs7917983, ZNF766_rs41497444 and TGFBR3_rs7526590. The odds ratio (OR) for increasing subcutaneous fat was higher by 2.232 folds in the high-GRS group, after adjusting for covariates. However, total and LDL cholesterol, triglyceride and C-reactive protein concentrations in the circulation were not associated with GRS. Subjects with high-GRS had higher serum HDL cholesterol levels than those with low-GRS. Physical activity and GRS had an interaction with subcutaneous fat. In subjects with low physical activity, the odds ratio for high subcutaneous fat increased by 2.232, but subcutaneous fat deposition was not affected in the high-GRS group with high physical activity.ConclusionObese adults with high-GRS had more subcutaneous fat, but they did not show more dyslipidemia and inflammation compared to low-GRS. High physical activity prevented subcutaneous fat deposition in subjects with high GRS for subcutaneous fat.

Whole‐genome analysis reveals the hybrid formation of Chinese indigenous DHB pig following human migration

“…Zhao et al ( 2018 ) also found that the IGF1R was selected in Meishan pigs, which may be related to the high fertility of this breed. SRC is related to food intake in mice (Yang et al, 2019 ), and ADCY2 is reported to affect human subcutaneous fat content, both of which are functionally relevant (Daily et al, 2019 ).…”

Interactions between Polygenic Risk Scores, Dietary Pattern, and Menarche Age with the Obesity Risk in a Large Hospital-Based Cohort

“…Furthermore, obesity-related genetic variants do not always equally influence obesity risk in different people because there are complex interactions between genetic and environmental factors, behavior, and the gut microbiota, influencing the actual obesity phenotypes. Recent studies have demonstrated that an individual genetic variant and lifestyle interactions influence the risk of obesity [13] and metabolic diseases [14,15] in Europeans and Asians [16]. For example, FTO genetic variants interact with the genetic and environmental factors that influence obesity risk [17,18].…”

Association Study Between Polymorphic Loci in Cholesterol Metabolism Pathway and Gallstone in the Tibetan Population

“…Our study showed that the alteration of rs4072341 in adenylyl cyclase 2 ( ADCY2 ) gene also reduced the occurrence of gallstones. In addition, ( Daily et al, 2019 ) found that ADCY2 rs326149 affects subcutaneous fat, which is positively correlated with the amount of subcutaneous fat, resulting in a high level of serum high-density lipoprotein cholesterol level. Previous studies have shown that ADCY2 gene is expressed in the brain and encodes a membrane-binding enzyme for the synthesis of cyclic adenosine monophosphate (cAMP).…”