Journal article
Endogenous Peroxisome Proliferator-Activated Receptor-gamma Augments Fatty Acid Uptake in Oxidative Muscle
Endocrinology (Philadelphia), Vol.149(11), pp.5374-5383
11/01/2008
DOI: 10.1210/en.2008-0100
PMCID: PMC2584586
PMID: 18653710
Abstract
In the setting of insulin resistance, agonists of peroxisome proliferator-activated receptor (PPAR)-gamma restore insulin action in muscle and promote lipid redistribution. Mice with muscle-specific knockout of PPAR gamma (MuPPAR gamma KO) develop excess adiposity, despite reduced food intake and normal glucose disposal in muscle. To understand the relation between muscle PPAR gamma and lipid accumulation, we studied the fuel energetics of MuPPAR gamma KO mice. Compared with controls, MuPPAR gamma KO mice exhibited significantly increased ambulatory activity, muscle mitochondrial uncoupling, and respiratory quotient. Fitting with this latter finding, MuPPAR gamma KO 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 MuPPAR gamma KO mice despite the increased expression of several genes promoting lipid oxidation. These data demonstrate that PPAR gamma, 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 PPAR gamma activity in muscle is absent or reduced, there will be decreased fatty acid disposal leading to diminished energy utilization and ultimately adiposity. (Endocrinology 149: 5374-5383, 2008)
Details
- Title: Subtitle
- Endogenous Peroxisome Proliferator-Activated Receptor-gamma Augments Fatty Acid Uptake in Oxidative Muscle
- Creators
- Andrew W. Norris - University of IowaMichael F. Hirshman - Harvard UniversityJianrong Yao - University of IowaNiels Jessen - Harvard UniversityNicolas Musi - Harvard UniversityLihong Chen - Harvard UniversityWilliam I. Sivitz - University of IowaLaurie J. Goodyear - Harvard UniversityC. Ronald Kahn - Harvard University
- Resource Type
- Journal article
- Publication Details
- Endocrinology (Philadelphia), Vol.149(11), pp.5374-5383
- DOI
- 10.1210/en.2008-0100
- PMID
- 18653710
- PMCID
- PMC2584586
- NLM abbreviation
- Endocrinology
- ISSN
- 0013-7227
- eISSN
- 1945-7170
- Publisher
- Endocrine Soc
- Number of pages
- 10
- Grant note
- K08DK064906 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) R01AR045670 / NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) DK25295; R01-DK60837; DK36836 / Joslin Diabetes Center Diabetes and Endocrinology Research Center Veterans Affairs Medical Research; US Department of Veterans Affairs K08-DK064906; R01-AR45670; R01-DK068626 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 11/01/2008
- Academic Unit
- Endocrinology and Diabetes; Stead Family Department of Pediatrics; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984293077802771
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