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FAM13A affects body fat distribution and adipocyte function.

  • Author(s): Fathzadeh, Mohsen;
  • Li, Jiehan;
  • Rao, Abhiram;
  • Cook, Naomi;
  • Chennamsetty, Indumathi;
  • Seldin, Marcus;
  • Zhou, Xiang;
  • Sangwung, Panjamaporn;
  • Gloudemans, Michael J;
  • Keller, Mark;
  • Attie, Allan;
  • Yang, Jing;
  • Wabitsch, Martin;
  • Carcamo-Orive, Ivan;
  • Tada, Yuko;
  • Lusis, Aldons J;
  • Shin, Myung Kyun;
  • Molony, Cliona M;
  • McLaughlin, Tracey;
  • Reaven, Gerald;
  • Montgomery, Stephen B;
  • Reilly, Dermot;
  • Quertermous, Thomas;
  • Ingelsson, Erik;
  • Knowles, Joshua W
  • et al.
Abstract

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.

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