The American journal of clinical nutrition
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Review
Regulation of skeletal muscle mitochondrial fatty acid metabolism in lean and obese individuals.
A reduction in fatty acid (FA) oxidation has been associated with lipid accumulation and insulin resistance in skeletal muscle of obese individuals. Numerous reports suggest that the reduction in FA oxidation may result from intrinsic mitochondrial defects, although little direct evidence has been offered to support this conclusion. This brief review summarizes recent work from our laboratory that reexamined whether this decrease in skeletal muscle FA oxidation with obesity was attributable to a dysfunction in FA oxidation within mitochondria or simply to a reduction in muscle mitochondrial content. ⋯ However, this did not result from decreased protein contents of various transcription factors, because peroxisome proliferater-activated receptor gamma coactivator 1alpha (PGC1alpha), PGC1beta, peroxisome proliferator-activated receptor alpha (PPARalpha), and mitochondrial transcription factor A (TFAM) were not reduced with obesity. In contrast, it appears that obesity is associated with altered regulation of cofactors (PGC1alpha and PGC1beta) and their downstream transcription factors (PPARalpha, PPARdelta/beta, and TFAM), because relations among these variables were present in muscle from lean individuals but not from obese individuals. These findings imply that obese individuals would benefit from interventions that increase the skeletal muscle mitochondrial content and the potential for oxidizing FAs.