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Regulation of skeletal muscle mitochondrial fatty acid metabolism in lean and obese individuals.
Am J Clin Nutr 2009; 89(1):455S-62SAJ

Abstract

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. Whole-muscle mitochondrial content and FA oxidation was reduced in the obese, but there was no decrease in the ability of isolated mitochondria to oxidize FA. The mitochondrial content of the transport protein, FA translocase (FAT/CD36), did not differ between lean and obese women but was correlated with mitochondrial FA oxidation. It was concluded that the reduced FA oxidation in obesity is attributable to decreased muscle mitochondrial content and not intrinsic defects in mitochondrial FA oxidation, and that mitochondrial FAT/CD36 is involved in regulating FA oxidation in human skeletal muscle. The reduced skeletal muscle mitochondrial content with obesity may result from impaired mitochondrial biogenesis. 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.

Authors+Show Affiliations

Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

19056573

Citation

Holloway, Graham P., et al. "Regulation of Skeletal Muscle Mitochondrial Fatty Acid Metabolism in Lean and Obese Individuals." The American Journal of Clinical Nutrition, vol. 89, no. 1, 2009, 455S-62S.
Holloway GP, Bonen A, Spriet LL. Regulation of skeletal muscle mitochondrial fatty acid metabolism in lean and obese individuals. Am J Clin Nutr. 2009;89(1):455S-62S.
Holloway, G. P., Bonen, A., & Spriet, L. L. (2009). Regulation of skeletal muscle mitochondrial fatty acid metabolism in lean and obese individuals. The American Journal of Clinical Nutrition, 89(1), 455S-62S. doi:10.3945/ajcn.2008.26717B.
Holloway GP, Bonen A, Spriet LL. Regulation of Skeletal Muscle Mitochondrial Fatty Acid Metabolism in Lean and Obese Individuals. Am J Clin Nutr. 2009;89(1):455S-62S. PubMed PMID: 19056573.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of skeletal muscle mitochondrial fatty acid metabolism in lean and obese individuals. AU - Holloway,Graham P, AU - Bonen,Arend, AU - Spriet,Lawrence L, Y1 - 2008/12/03/ PY - 2008/12/6/pubmed PY - 2009/2/6/medline PY - 2008/12/6/entrez SP - 455S EP - 62S JF - The American journal of clinical nutrition JO - Am. J. Clin. Nutr. VL - 89 IS - 1 N2 - 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. Whole-muscle mitochondrial content and FA oxidation was reduced in the obese, but there was no decrease in the ability of isolated mitochondria to oxidize FA. The mitochondrial content of the transport protein, FA translocase (FAT/CD36), did not differ between lean and obese women but was correlated with mitochondrial FA oxidation. It was concluded that the reduced FA oxidation in obesity is attributable to decreased muscle mitochondrial content and not intrinsic defects in mitochondrial FA oxidation, and that mitochondrial FAT/CD36 is involved in regulating FA oxidation in human skeletal muscle. The reduced skeletal muscle mitochondrial content with obesity may result from impaired mitochondrial biogenesis. 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. SN - 1938-3207 UR - https://www.unboundmedicine.com/medline/citation/19056573/Regulation_of_skeletal_muscle_mitochondrial_fatty_acid_metabolism_in_lean_and_obese_individuals_ L2 - https://academic.oup.com/ajcn/article-lookup/doi/10.3945/ajcn.2008.26717B DB - PRIME DP - Unbound Medicine ER -