Critical roles of the p160 transcriptional coactivators p/CIP and SRC-1 in energy balance

Zhiyong Wang*, Chao Qi, Anna Krones, Pamela Woodring, Xiaoyan Zhu, Janardan K. Reddy, Ronald M. Evans, Michael G. Rosenfeld, Tony Hunter

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

80 Scopus citations


Several transcriptional coactivators have been implicated in modulating the transcriptional activities of nuclear hormone receptors in vitro. Potential roles of these cofactors in important physiological processes such as energy homeostasis remain unknown. We report here that a developmental arrest in interscapular brown fat and defective adaptive thermogenesis occur in mice lacking both the p160 family transcriptional coactivators SRC-1 and p/CIP due to a failure in induction of selective PPARγ target genes involved in adipogenesis and mitochondrial uncoupling. In the absence of p/CIP and SRC-1, mice eat more food on both regular chow and a high-fat diet because of decreased blood leptin levels. However, the p/CIP-/-/SRC-1-/- mice are lean and resistant to high-fat-diet-induced obesity. They exhibit increased basal metabolic rates and heightened levels of physical activity. Therefore, p/CIP and SRC-1 play critical roles in energy balance by controlling both energy intake and energy expenditure.

Original languageEnglish (US)
Pages (from-to)111-122
Number of pages12
JournalCell Metabolism
Issue number2
StatePublished - Feb 2006


  • DNA
  • Humdisease

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology


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