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

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

Research output: Contribution to journalArticle

514 Citations (Scopus)

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

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Peroxisome Proliferator-Activated Receptors
PPAR gamma
p38 Mitogen-Activated Protein Kinases
Energy Metabolism
Cytokines
Interleukin-1
Muscles
Cachexia
Muscle Cells
Lipopolysaccharides
Cultured Cells
Respiration
Phosphotransferases
Phosphorylation
Gene Expression
Infection
Neoplasms
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Cytokine Stimulation of Energy Expenditure through p38 MAP Kinase Activation of PPARγ Coactivator-1. / Puigserver, Pere; Rhee, James; Lin, Jiandie; Wu, Zhidan; Yoon, John; Zhang, Chen Yu; Krauss, Stefan; Mootha, Vamsi K.; Lowell, Bradford B.; Spiegelman, Bruce M.

In: Molecular Cell, Vol. 8, No. 5, 21.11.2001, p. 971-982.

Research output: Contribution to journalArticle

Puigserver, P, Rhee, J, Lin, J, Wu, Z, Yoon, J, Zhang, CY, Krauss, S, Mootha, VK, Lowell, BB & Spiegelman, BM 2001, 'Cytokine Stimulation of Energy Expenditure through p38 MAP Kinase Activation of PPARγ Coactivator-1', Molecular Cell, vol. 8, no. 5, pp. 971-982. https://doi.org/10.1016/S1097-2765(01)00390-2
Puigserver, Pere ; Rhee, James ; Lin, Jiandie ; Wu, Zhidan ; Yoon, John ; Zhang, Chen Yu ; Krauss, Stefan ; Mootha, Vamsi K. ; Lowell, Bradford B. ; Spiegelman, Bruce M. / Cytokine Stimulation of Energy Expenditure through p38 MAP Kinase Activation of PPARγ Coactivator-1. In: Molecular Cell. 2001 ; Vol. 8, No. 5. pp. 971-982.
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