• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma.

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.

Pubmed ID: 15175761


  • Picard F
  • Kurtev M
  • Chung N
  • Topark-Ngarm A
  • Senawong T
  • Machado De Oliveira R
  • Leid M
  • McBurney MW
  • Guarente L



Publication Data

June 17, 2004

Associated Grants

  • Agency: NIGMS NIH HHS, Id: R01 GM060852
  • Agency: NIGMS NIH HHS, Id: R01 GM060852-02

Mesh Terms

  • 3T3-L1 Cells
  • Adipocytes
  • Animals
  • Biological Transport
  • Caloric Restriction
  • Cell Line
  • DNA-Binding Proteins
  • Gene Deletion
  • Gene Expression
  • Humans
  • Lipid Metabolism
  • Lipolysis
  • Longevity
  • Mice
  • Nuclear Proteins
  • Nuclear Receptor Co-Repressor 1
  • Nuclear Receptor Co-Repressor 2
  • RNA Interference
  • Receptors, Cytoplasmic and Nuclear
  • Repressor Proteins
  • Sirtuin 1
  • Sirtuins
  • Stilbenes
  • Transcription Factors
  • Triglycerides