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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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