Endogenous peroxisome proliferator-activated receptor-γ augments fatty acid uptake in oxidative muscle

Andrew W. Norris, Michael F. Hirshman, Jianrong Yao, Niels Jessen, Nicolas Musi, Lihong Chen, William I. Sivitz, Laurie J. Goodyear, C. Ronald Kahn

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


In the setting of insulin resistance, agonists of peroxisome proliferator-activated receptor (PPAR)-γ restore insulin action in muscle and promote lipid redistribution. Mice with muscle-specific knockout of PPARγ (MuPPARγKO) develop excess adiposity, despite reduced food intake and normal glucose disposal in muscle. To understand the relation between muscle PPARγ and lipid accumulation, we studied the fuel energetics of MuPPARγKO mice. Compared with controls, MuPPARγKO mice exhibited significantly increased ambulatory activity, muscle mitochondrial uncoupling, and respiratory quotient. Fitting with this latter finding, MuPPARγKO animals compared with control siblings exhibited a 25% reduction in the uptake of the fatty acid tracer 2-bromo-palmitate (P < 0.05) and a 13% increase in serum nonesterified fatty acids (P = 0.05). These abnormalities were associated with no change in AMP kinase (AMPK) phosphorylation, AMPK activity, or phosphorylation of acetyl-CoA carboxylase in muscle and occurred despite increased expression of fatty acid transport protein 1. Palmitate oxidation was not significantly altered in MuPPARγKO mice despite the increased expression of several genes promoting lipid oxidation. These data demonstrate that PPARγ, even in the absence of exogenous activators, is required for normal rates of fatty acid uptake in oxidative skeletal muscle via mechanisms independent of AMPK and fatty acid transport protein 1. Thus, when PPARγ activity in muscle is absent or reduced, there will be decreased fatty acid disposal leading to diminished energy utilization and ultimately adiposity.

Original languageEnglish (US)
Pages (from-to)5374-5383
Number of pages10
Issue number11
StatePublished - Nov 2008
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology


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