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Status |
Public on Mar 06, 2012 |
Title |
PPARg agonists induce a white-to-brown fat conversion through stabilization of PRDM16 protein |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
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 novel therapeutic pathway for the treatment of obesity and diabetes.
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Overall design |
Microarray analysis of the differentiated inguinal adipocytes expressing sh-scr or sh-PRDM16 in the presence or absence of rosiglitazone (1uM). These samples were profiled using Affymetrix mouse 430A_2 arrays, representing 2 biological replicates for each samples (8 samples in total).
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Contributor(s) |
Ohno H, Shinoda K, Spiegelman BM, Kajimura S |
Citation(s) |
22405074 |
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Submission date |
Jan 11, 2012 |
Last update date |
May 04, 2018 |
Contact name |
Kosaku Shinoda |
E-mail(s) |
[email protected]
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Phone |
415-476-9736
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Fax |
415-514-2346
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URL |
http://www.diabetes.ucsf.edu/members/shingo-kajimura
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Organization name |
University of California, San Francisco
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Department |
UCSF Diabetes Center and Department of Cell and Tissue Biology
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Street address |
35 Medical Center Way
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City |
San Francisco |
ZIP/Postal code |
94143-0669 |
Country |
USA |
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Platforms (1) |
GPL8321 |
[Mouse430A_2] Affymetrix Mouse Genome 430A 2.0 Array |
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Samples (8)
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Relations |
BioProject |
PRJNA151167 |