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FAM13A affects body fat distribution and adipocyte function

Author

Listed:
  • Mohsen Fathzadeh

    (Stanford University School of Medicine
    Stanford University
    Stanford University)

  • Jiehan Li

    (Stanford University School of Medicine
    Stanford University
    Stanford University)

  • Abhiram Rao

    (Stanford University School of Medicine
    School of Engineering and Medicine)

  • Naomi Cook

    (Uppsala University)

  • Indumathi Chennamsetty

    (Stanford University School of Medicine
    Stanford University)

  • Marcus Seldin

    (David Geffen School of Medicine, UCLA)

  • Xiang Zhou

    (Stanford University School of Medicine
    Stanford University)

  • Panjamaporn Sangwung

    (Stanford University School of Medicine
    Stanford University
    Stanford University)

  • Michael J. Gloudemans

    (Stanford University)

  • Mark Keller

    (University of Wisconsin)

  • Allan Attie

    (University of Wisconsin)

  • Jing Yang

    (University of Illinois at Urbana–Champaign)

  • Martin Wabitsch

    (University of Ulm)

  • Ivan Carcamo-Orive

    (Stanford University School of Medicine
    Stanford University
    Stanford University)

  • Yuko Tada

    (Stanford University School of Medicine
    Stanford University)

  • Aldons J. Lusis

    (David Geffen School of Medicine, UCLA)

  • Myung Kyun Shin

    (Genetics and Pharmacogenomics, Merck & Co., Inc.)

  • Cliona M. Molony

    (Genetics and Pharmacogenomics, Merck & Co., Inc.)

  • Tracey McLaughlin

    (Stanford University
    Stanford University School of Medicine)

  • Gerald Reaven

    (Stanford University School of Medicine
    Stanford University
    Stanford University)

  • Stephen B. Montgomery

    (Stanford University
    Stanford University
    Stanford University School of Medicine
    Stanford University)

  • Dermot Reilly

    (Genetics and Pharmacogenomics, Merck & Co., Inc.)

  • Thomas Quertermous

    (Stanford University School of Medicine
    Stanford University
    Stanford University)

  • Erik Ingelsson

    (Stanford University School of Medicine
    Stanford University
    Stanford University)

  • Joshua W. Knowles

    (Stanford University School of Medicine
    Stanford University
    Stanford University)

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.

Suggested Citation

  • Mohsen Fathzadeh & Jiehan Li & Abhiram Rao & Naomi Cook & Indumathi Chennamsetty & Marcus Seldin & Xiang Zhou & Panjamaporn Sangwung & Michael J. Gloudemans & Mark Keller & Allan Attie & Jing Yang & M, 2020. "FAM13A affects body fat distribution and adipocyte function," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15291-z
    DOI: 10.1038/s41467-020-15291-z
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