PPARγ agonists induce a white-to-brown fat conversion through stabilization of PRDM16 protein

Haruya Ohno, Kosaku Shinoda, Bruce M. Spiegelman, Shingo Kajimura

Research output: Contribution to journalArticle

351 Citations (Scopus)

Abstract

Brown adipose tissue dissipates energy through heat and functions as a defense against cold and obesity. PPARγ ligands have been shown to induce the browning of white adipocytes; however, the underlying mechanisms remain unclear. Here, we show that PPARγ ligands require full agonism to induce a brown fat gene program preferentially in subcutaneous white adipose. These effects require expression of PRDM16, a factor that controls the development of classical brown fat. Depletion of PRDM16 blunts the effects of the PPARγ agonist rosiglitazone on the induced brown fat gene program. Conversely, PRDM16 and rosiglitazone synergistically activate the brown fat gene program in vivo. This synergy is tightly associated with an increased accumulation of PRDM16 protein, due in large measure to an increase in the half-life of the protein in agonist treated cells. Identifying compounds that stabilize PRDM16 protein may represent a plausible therapeutic pathway for the treatment of obesity and diabetes.

Original languageEnglish (US)
Pages (from-to)395-404
Number of pages10
JournalCell Metabolism
Volume15
Issue number3
DOIs
StatePublished - Mar 7 2012
Externally publishedYes

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Peroxisome Proliferator-Activated Receptors
Brown Adipose Tissue
rosiglitazone
Proteins
Obesity
White Adipocytes
Genes
Ligands
Half-Life
Hot Temperature

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

PPARγ agonists induce a white-to-brown fat conversion through stabilization of PRDM16 protein. / Ohno, Haruya; Shinoda, Kosaku; Spiegelman, Bruce M.; Kajimura, Shingo.

In: Cell Metabolism, Vol. 15, No. 3, 07.03.2012, p. 395-404.

Research output: Contribution to journalArticle

Ohno, Haruya ; Shinoda, Kosaku ; Spiegelman, Bruce M. ; Kajimura, Shingo. / PPARγ agonists induce a white-to-brown fat conversion through stabilization of PRDM16 protein. In: Cell Metabolism. 2012 ; Vol. 15, No. 3. pp. 395-404.
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