BMP-TAK1 (MAP3K7) Induces Adipocyte Differentiation Through PPARγ Signaling.
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.
Center for Musculoskeletal Research, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, New York 14642.|Department of Biochemistry and Biophysics, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, New York 14642.|Center for Human Development and Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, New York 10032.
Yongchun
Y
Zhang
Department of Orthopaedic Surgery, Washington University School of Medicine, 660 Euclid Avenue, St. Louis, Missouri 63110.
Regis J
RJ
O'Keefe
Center for Musculoskeletal Research, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, New York 14642.|Department of Orthopaedics and Rehabilitation, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, New York 14642.
Jennifer H
JH
Jonason
D041721:3T3-L1 Cells; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology; D000099151:MAP Kinase Kinase Kinase 7
D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D020930:MAP Kinase Kinase Kinases; D047495:PPAR gamma; D000099151:MAP Kinase Kinase Kinase 7; C531463:Tab1 protein, mouse
ADIPOCYTE; BMP; OBESITY; PPARγ; TAK1