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FAM13A affects body fat distribution and adipocyte function.

Nat Commun. 2020 Mar 19;11(1):1465
Mohsen Fathzadeh 1 , Jiehan Li 1 , Abhiram Rao 2 , Naomi Cook 3 , Indumathi Chennamsetty 4 , Marcus Seldin 5 , Xiang Zhou 4 , Panjamaporn Sangwung 1 , Michael J Gloudemans 6 , Mark Keller 7 , Allan Attie 7 , Jing Yang 8 , Martin Wabitsch 9 , Ivan Carcamo-Orive 1 , Yuko Tada 4 , Aldons J Lusis 5 , Myung Kyun Shin 10 , Cliona M Molony 10 , Tracey McLaughlin 11 , Gerald Reaven 1 , Stephen B Montgomery 12 , Dermot Reilly 10 , Thomas Quertermous 1 , Erik Ingelsson 13 , Joshua W Knowles 14
Mohsen Fathzadeh 1 , Jiehan Li 1 , Abhiram Rao 2 , Naomi Cook 3 , Indumathi Chennamsetty 4 , Marcus Seldin 5 , Xiang Zhou 4 , Panjamaporn Sangwung 1 , Michael J Gloudemans 6 , Mark Keller 7 , Allan Attie 7 , Jing Yang 8 , Martin Wabitsch 9 , Ivan Carcamo-Orive 1 , Yuko Tada 4 , Aldons J Lusis 5 , Myung Kyun Shin 10 , Cliona M Molony 10 , Tracey McLaughlin 11 , Gerald Reaven 1 , Stephen B Montgomery 12 , Dermot Reilly 10 , Thomas Quertermous 1 , Erik Ingelsson 13 , Joshua W Knowles 14
+ et al

[No authors listed]

Author information
  • 1 Stanford Diabetes Research Center, Stanford University, Stanford, CA, USA.
  • 2 Bioengineering Department, School of Engineering and Medicine, Stanford, CA, USA.
  • 3 Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala, Sweden.
  • 4 Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA.
  • 5 Department of Human Genetics, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  • 6 Department of Genetics, Stanford University, California, CA, USA.
  • 7 Department of Biochemistry, University of Wisconsin, Madison, WI, USA.
  • 8 Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
  • 9 Division of Paediatric Endocrinology and Diabetes, Department of Paediatrics and Adolescent Medicine, University of Ulm, Ulm, Germany.
  • 10 Genetics and Pharmacogenomics, Merck & Co., Inc., Kenilworth, NJ, USA.
  • 11 Department of Medicine, Division of Endocrinology, Stanford University School of Medicine, Stanford, CA, USA.
  • 12 Department of Pathology, Stanford University, California, CA, USA.
  • 13 Stanford Diabetes Research Center, Stanford University, Stanford, CA, USA. eriking@stanford.edu.
  • 14 Stanford Diabetes Research Center, Stanford University, Stanford, CA, USA. knowlej@stanford.edu.

摘要

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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