FAM13A 影响体脂肪分布和脂肪细胞功能。

FAM13A affects body fat distribution and adipocyte function.

机构信息

Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.

Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA.

出版信息

Nat Commun. 2020 Mar 19;11(1):1465. doi: 10.1038/s41467-020-15291-z.

Genetic variation in the FAM13A (Family with Sequence Similarity 13 Member A) locus has been associated with several glycemic and metabolic traits in genome-wide association studies (GWAS). Here, we demonstrate that in humans, FAM13A alleles are associated with increased FAM13A expression in subcutaneous adipose tissue (SAT) and an insulin resistance-related phenotype (e.g. higher waist-to-hip ratio and fasting insulin levels, but lower body fat). In human adipocyte models, knockdown of FAM13A in preadipocytes accelerates adipocyte differentiation. In mice, Fam13a knockout (KO) have a lower visceral to subcutaneous fat (VAT/SAT) ratio after high-fat diet challenge, in comparison to their wild-type counterparts. Subcutaneous adipocytes in KO mice show a size distribution shift toward an increased number of smaller adipocytes, along with an improved adipogenic potential. Our results indicate that GWAS-associated variants within the FAM13A locus alter adipose FAM13A expression, which in turn, regulates adipocyte differentiation and contribute to changes in body fat distribution.

FAM13A（家族与序列相似性 13 成员 A）基因座的遗传变异与全基因组关联研究（GWAS）中的几种血糖和代谢特征有关。在这里，我们证明在人类中，FAM13A 等位基因与皮下脂肪组织（SAT）中 FAM13A 表达的增加以及与胰岛素抵抗相关的表型（例如，更高的腰臀比和空腹胰岛素水平，但体脂较低）有关。在人类脂肪细胞模型中，脂肪前体细胞中的 FAM13A 敲低加速了脂肪细胞的分化。在小鼠中，与野生型相比，高脂肪饮食挑战后 Fam13a 敲除（KO）小鼠的内脏到皮下脂肪（VAT/SAT）比例较低。KO 小鼠的皮下脂肪细胞表现出大小分布向更多较小脂肪细胞的数量转移，同时脂肪生成潜力得到改善。我们的结果表明，GWAS 相关变异体在 FAM13A 基因座内改变脂肪 FAM13A 的表达，这反过来又调节脂肪细胞分化，并导致体脂分布的变化。