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 language | English (US) |
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Pages (from-to) | 971-982 |
Number of pages | 12 |
Journal | Molecular Cell |
Volume | 8 |
Issue number | 5 |
DOIs | |
State | Published - Nov 21 2001 |
Externally published | Yes |
ASJC Scopus subject areas
- Molecular Biology