Myostatin inhibits brown adipocyte differentiation via regulation of Smad3-mediated β-catenin stabilization

Won Kon Kim, Hye Ryung Choi, Sung Goo Park, Yong Ko, Kwang Hee Bae, Sang Chul Lee

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)

Abstract

Brown adipocytes play an important role in regulating energy balance, and there is a good correlation between obesity and the amount of brown adipose tissue. Although the molecular mechanism of white adipocyte differentiation has been well characterized, brown adipogenesis has not been studied extensively. Moreover, extracellular factors that regulate brown adipogenic differentiation are not fully understood. Here, we assessed the mechanism of the regulatory action of myostatin in brown adipogenic differentiation using primary brown preadipocytes. Our results clearly showed that differentiation of brown adipocytes was significantly inhibited by myostatin treatment. In addition, myostatin-induced suppression of brown adipogenesis was observed during the early phase of differentiation. Myostatin induced the phosphorylation of Smad3, which led to increased β-catenin stabilization. These effects were blocked by treatment with a Smad3 inhibitor. Expression of brown adipocyte-related genes, such as PPAR-γ, UCP-1, PGC-1α, and PRDM16, were dramatically down-regulated by treatment with myostatin, and further down-regulated by co-treatment with a β-catenin activator. Taken together, the present study demonstrated that myostatin is a potent negative regulator of brown adipogenic differentiation by modulation of Smad3-induced β-catenin stabilization. Our findings suggest that myostatin could be used as an extracellular factor in the control of brown adipocyte differentiation.

Original languageEnglish
Pages (from-to)327-334
Number of pages8
JournalInternational Journal of Biochemistry and Cell Biology
Volume44
Issue number2
DOIs
Publication statusPublished - 2012 Feb

Keywords

  • Adipogenesis
  • Brown adipocytes
  • Myostatin
  • Smad3
  • β-Catenin

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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