2. Academic Validation
  3. BMP-TAK1 (MAP3K7) Induces Adipocyte Differentiation Through PPARγ Signaling

BMP-TAK1 (MAP3K7) Induces Adipocyte Differentiation Through PPARγ Signaling

  • J Cell Biochem. 2017 Jan;118(1):204-210. doi: 10.1002/jcb.25626.
Yongchun Zhang 1 2 3,  Regis J O'Keefe 4,  Jennifer H Jonason 1 5
Affiliations

Affiliations

  • 1 Center for Musculoskeletal Research, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, New York 14642.
  • 2 Department of Biochemistry and Biophysics, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, New York 14642.
  • 3 Center for Human Development and Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, New York 10032.
  • 4 Department of Orthopaedic Surgery, Washington University School of Medicine, 660 Euclid Avenue, St. Louis, Missouri 63110.
  • 5 Department of Orthopaedics and Rehabilitation, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, New York 14642.
PMID: 27293199 DOI: 10.1002/jcb.25626
Abstract

BMPs have been shown to promote adipocyte differentiation through SMAD-dependent signaling. However, the role of TGF-β-activated kinase 1 (TAK1) in non-canonical BMP signaling in adipocyte differentiation remains unclear. Here, we show that TAK1 inhibition decreases lipid accumulation in C3H10T1/2 mesenchymal stem cells (MSCs) induced to differentiate into adipocytes. TAK1 knockdown by siRNA further confirms that TAK1 is required for adipocyte commitment of MSCs. Additionally, TAK1 knockdown inhibits adipogenesis of 3T3-L1 preadipocytes, indicating that TAK1 is not only needed for adipocyte commitment, but also required for adipocyte terminal differentiation. Furthermore, TAK1 ablation specifically in adipocytes reduced high fat diet-induced weight gain and improved glucose tolerance. Mechanistically, we demonstrate that TAK1 is required for PPARγ transactivation and promotes PPARγ transcriptional activity synergistically with TAK1 binding protein 1 (TAB1). Collectively, our results demonstrate that TAK1 plays a critical role in BMP-mediated adipocyte differentiation. J. Cell. Biochem. 118: 204-210, 2017. © 2016 Wiley Periodicals, Inc.

Keywords

ADIPOCYTE; BMP; OBESITY; PPARγ; TAK1.

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