High-fat diets cause insulin resistance despite an increase in muscle mitochondria
- PMID: 18509063
- PMCID: PMC2409421
- DOI: 10.1073/pnas.0802057105
High-fat diets cause insulin resistance despite an increase in muscle mitochondria
Abstract
It has been hypothesized that insulin resistance is mediated by a deficiency of mitochondria in skeletal muscle. In keeping with this hypothesis, high-fat diets that cause insulin resistance have been reported to result in a decrease in muscle mitochondria. In contrast, we found that feeding rats high-fat diets that cause muscle insulin resistance results in a concomitant gradual increase in muscle mitochondria. This adaptation appears to be mediated by activation of peroxisome proliferator-activated receptor (PPAR)delta by fatty acids, which results in a gradual, posttranscriptionally regulated increase in PPAR gamma coactivator 1alpha (PGC-1alpha) protein expression. Similarly, overexpression of PPARdelta results in a large increase in PGC-1alpha protein in the absence of any increase in PGC-1alpha mRNA. We interpret our findings as evidence that raising free fatty acids results in an increase in mitochondria by activating PPARdelta, which mediates a posttranscriptional increase in PGC-1alpha. Our findings argue against the concept that insulin resistance is mediated by a deficiency of muscle mitochondria.
Conflict of interest statement
The authors declare no conflict of interest.
Figures
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Comment in
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Muscle insulin resistance: a case of fat overconsumption, not mitochondrial dysfunction.Proc Natl Acad Sci U S A. 2008 Jun 3;105(22):7627-8. doi: 10.1073/pnas.0803901105. Epub 2008 May 28. Proc Natl Acad Sci U S A. 2008. PMID: 18509057 Free PMC article. No abstract available.
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