Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma
Language: 
English
Abstract: 

Calorie restriction extends lifespan in organisms ranging from yeast to mammals. In yeast, the SIR2 gene mediates the life-extending effects of calorie restriction. Here we show that the mammalian SIR2 orthologue, Sirt1 (sirtuin 1), activates a critical component of calorie restriction in mammals; that is, fat mobilization in white adipocytes. Upon food withdrawal Sirt1 protein binds to and represses genes controlled by the fat regulator PPAR-gamma (peroxisome proliferator-activated receptor-gamma), including genes mediating fat storage. Sirt1 represses PPAR-gamma by docking with its cofactors NCoR (nuclear receptor co-repressor) and SMRT (silencing mediator of retinoid and thyroid hormone receptors). Mobilization of fatty acids from white adipocytes upon fasting is compromised in Sirt1+/- mice. Repression of PPAR-gamma by Sirt1 is also evident in 3T3-L1 adipocytes, where overexpression of Sirt1 attenuates adipogenesis, and RNA interference of Sirt1 enhances it. In differentiated fat cells, upregulation of Sirt1 triggers lipolysis and loss of fat. As a reduction in fat is sufficient to extend murine lifespan, our results provide a possible molecular pathway connecting calorie restriction to life extension in mammals.

Author(s): 
Picard, FrÈdÈric
Kurtev, Martin
Chung, Namjin
Topark-Ngarm, Acharawan
Senawong, Thanaset
Machado De Oliveira, Rita
Leid, Mark
McBurney, Michael W.
Guarente, Leonard
Item Type: 
Journal Article
Publication Title: 
Nature
Journal Abbreviation: 
Nature
Publication Date: 
6/17/2004
Publication Year: 
2004
Pages: 
771-776
Volume: 
429
Issue: 
6993
ISSN: 
1476-4687
DOI: 
10.1038/nature02583
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 15175761 PMCID: PMC2820247

Turabian/Chicago Citation

FrÈdÈric Picard, Martin Kurtev, Namjin Chung, Acharawan Topark-Ngarm, Thanaset Senawong, Rita Machado De Oliveira, Mark Leid, Michael W. McBurney and Leonard Guarente. 6/17/2004. "Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma." Nature 429: 6993: 771-776. 10.1038/nature02583.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1038/nature02583 | issn = 1476-4687 | volume = 429 | pages = 771-776 | last = Picard | first = FrÈdÈric | coauthors = Kurtev, Martin, Chung, Namjin, Topark-Ngarm, Acharawan, Senawong, Thanaset, Machado De Oliveira, Rita, Leid, Mark, McBurney, Michael W., Guarente, Leonard | title = Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma | journal = Nature | date = 6/17/2004 | pmid = | pmc = }} </ref>