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High-fat diets cause insulin resistance despite an increase in muscle mitochondria
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High-fat diets cause insulin resistance despite an increase in muscle mitochondria
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Journal Article
High-fat diets cause insulin resistance despite an increase in muscle mitochondria
2008
Overview
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)δ by fatty acids, which results in a gradual, posttranscriptionally regulated increase in PPAR γ coactivator 1α (PGC-1α) protein expression. Similarly, overexpression of PPARδ results in a large increase in PGC-1α protein in the absence of any increase in PGC-1α mRNA. We interpret our findings as evidence that raising free fatty acids results in an increase in mitochondria by activating PPARδ, which mediates a posttranscriptional increase in PGC-1α. Our findings argue against the concept that insulin resistance is mediated by a deficiency of muscle mitochondria.
Publisher
National Academy of Sciences,National Acad Sciences
Subject
/ Animals
/ Diet
/ Dietary Fats - administration & dosage
/ Fatty Acids, Nonesterified - blood
/ Fatty Acids, Nonesterified - metabolism
/ Insulin
/ Male
/ Mitochondria, Muscle - drug effects
/ Mitochondria, Muscle - metabolism
/ Muscle, Skeletal - drug effects
/ Muscle, Skeletal - metabolism
/ Muscle, Skeletal - ultrastructure
/ Muscles
/ peroxisome proliferator-activated receptor alpha
/ peroxisome proliferator-activated receptor alpha coactivator
/ Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
/ Proteins
/ Rats
/ Rodents
