Cytokine Stimulation of Energy Expenditure through p38 MAP Kinase Activation of PPARγ Coactivator-1

Pere Puigserver, James Rhee, Jiandie Lin, Zhidan Wu, J. Cliff Yoon, Chen Yu Zhang, Stefan Krauss, Vamsi K. Mootha, Bradford B. Lowell, Bruce M. Spiegelman

Research output: Contribution to journalArticlepeer-review

Abstract

Cachexia is a chronic state of negative energy balance and muscle wasting that is a severe complication of cancer and chronic infection. While cytokines such as IL-1α, IL-1β, and TNFα can mediate cachectic states, how these molecules affect energy expenditure is unknown. We show here that many cytokines activate the transcriptional PPAR gamma coactivator-1 (PGC-1) through phosphorylation by p38 kinase, resulting in stabilization and activation of PGC-1 protein. Cytokine or lipopolysaccharide (LPS)-induced activation of PGC-1 in cultured muscle cells or muscle in vivo causes increased respiration and expression of genes linked to mitochondrial uncoupling and energy expenditure. These data illustrate a direct thermogenic action of cytokines and p38 MAP kinase through the transcriptional coactivator PGC-1.

Original languageEnglish (US)
Pages (from-to)971-982
Number of pages12
JournalMolecular Cell
Volume8
Issue number5
DOIs
StatePublished - Nov 21 2001
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology

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