Medical Department III-Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, 04103 Leipzig, Germany.
Clinic for Visceral, Transplantation and Thorax and Vascular Surgery, University Hospital Leipzig, 04103 Leipzig, Germany.
Int J Mol Sci. 2022 Aug 2;23(15):8558. doi: 10.3390/ijms23158558.
locus has been shown to be associated with body fat distribution (FD), but neither the causal gene nor its role in metabolic diseases has been elucidated. We hypothesize that may act as the causal genes for FD-related SNPs (rs10195252 and rs6738627), and that they may be regulated by SNP to effect obesity-related metabolic traits. We genotyped rs10195252 and rs6738627 in 2860 subjects with metabolic phenotypes. In a subgroup of 560 subjects, we analyzed gene expression in paired visceral and subcutaneous adipose tissue (AT) samples. Mediation analyses were used to determine the causal relationship between SNPs, AT mRNA expression, and obesity-related traits. In vitro gene knockdown of was used to test their role in adipogenesis. Both gene expressions in AT are correlated with waist circumference. Visceral mRNA expression is associated with FPG and HbA1c. Both SNPs are associated with triglycerides, FPG, and leptin levels. Rs10195252 is associated with HbA1c and seems to be mediated by visceral AT mRNA expression. Our data support the role of the gene expression in body FD and its locus in metabolic sequelae: in particular, lipid metabolism and glucose homeostasis, which is likely mediated by AT transcript levels.
已经证实，locus 与体脂肪分布（FD）有关，但因果基因及其在代谢疾病中的作用尚未阐明。我们假设 可能是与 FD 相关 SNP（rs10195252 和 rs6738627）有关的因果基因，它们可能受 SNP 调控，影响肥胖相关的代谢特征。我们在 2860 名具有代谢表型的受试者中对 rs10195252 和 rs6738627 进行了基因分型。在 560 名亚组受试者中，我们分析了配对的内脏和皮下脂肪组织（AT）样本中的 基因表达。中介分析用于确定 SNP、AT mRNA 表达与肥胖相关特征之间的因果关系。我们还使用体外基因敲低技术测试了 基因在脂肪生成中的作用。AT 中的两种基因表达均与腰围相关。内脏 mRNA 表达与 FPG 和 HbA1c 相关。两种 SNP 均与甘油三酯、FPG 和瘦素水平相关。rs10195252 与 HbA1c 相关，似乎由内脏 AT 中的 mRNA 表达介导。我们的数据支持 基因表达在体 FD 及其在代谢后果中的作用：特别是脂代谢和血糖稳态，这可能是由 AT 转录水平介导的。
