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.
Highlights
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-Genetic risk scores (GRS) group with high physical activity
High subcutaneous fat and low visceral fat (HS-LV) and Low subcutaneous fat and low visceral fat (LS-LV) groups were younger than the High subcutaneous fat and high visceral fat (HS-HV) and Low subcutaneous fat and high visceral fat (LS-HV) groups (P < 0.001), indicating that subjects with high visceral fat mass were older than those with low visceral fat regardless of subcutaneous fat mass
Age was a good determinant for visceral fat mass, since visceral fat mass increased with increasing age (P < 0.001; Table 1)
Summary
High circulating free fatty acid levels by lipolysis increases insulin resistance by stimulating very low-density lipoprotein (VLDL) production in the liver. The increase of serum free fatty acid and proinflammatory cytokine concentrations, mainly from visceral fat, leads to insulin resistance which promotes metabolic diseases [4]. A recent study [5] has demonstrated that subcutaneous fat tissue is the largest fat depot in the body, and its lipolysis may influence the increase serum free fatty acid levels. A high lipolysis rate from subcutaneous fat depot may induce hypertriglyceridemia and low HDL and subcutaneous fat tissue may lead to dyslipidemia [5] It is still uncertain whether the subcutaneous fat depot influences the development of metabolic diseases. 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
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