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PGC-1alpha's relationship with skeletal muscle palmitate oxidation is not present with obesity despite maintained PGC-1alpha and PGC-1beta protein.
Am J Physiol Endocrinol Metab 2008; 294(6):E1060-9AJ

Abstract

Reduced skeletal muscle mitochondrial content and fatty acid oxidation are associated with obesity and insulin resistance. Although the exact mechanisms remain elusive, this may result from impaired mitochondrial biogenesis or reductions in the mitochondrial reticulum network. Therefore, the purpose of this study was to determine whether the protein contents of various transcription factors, including PGC-1alpha and PGC-1beta and proteins associated with mitochondrial fusion events, were reduced in skeletal muscle of nine obese (BMI = 37.6 +/- 2.2 kg/m(-2)) compared with nine age-matched lean (BMI = 23.3 +/- 0.7 kg/m(-2)) women. The protein contents of PGC-1alpha, PGC-1beta, PPARalpha, and tFAM were not reduced with obesity. In contrast, PPARgamma was increased (+22%, P < 0.05) with obesity, and there was a trend toward an increase (+31%, P = 0.13) in PPARdelta/beta. In lean individuals, PGC-1alpha protein correlated with citrate synthase (CS; r = 0.67) and rates of palmitate oxidation (r = 0.87), whereas PGC-1beta correlated with PPARgamma (r = 0.90), PPARdelta/beta (r = 0.63), and cytochrome c oxidase IV (COX-IV; r = 0.63). In obese individuals, the relationship between PGC-1alpha and CS was maintained (r = 0.65); however, the associations between PGC-1alpha and palmitate oxidation (r = -0.38) and PGC-1beta with PPARgamma (r = 0.14), PPARdelta/beta (r = 0.21), and COX-IV (r = 0.01) were lost. In addition, mitofusin-1 (MFN-1), MFN-2, and dynamin-related protein-1 (DRP-1) total protein contents were not altered with obesity (P > 0.05). These data suggest that altered regulation, and not reductions in the protein contents of transcription factors, is associated with insulin resistance. Also, it does not appear that alterations in the proteins associated with mitochondrial network formation and degradation can account for the observed decrease in mitochondrial content.

Authors+Show Affiliations

Human Health & Nutritional Sciences, University of Guelph, Guelph, ON, Canada. ghollowa@uoguelph.caNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

18349111

Citation

Holloway, Graham P., et al. "PGC-1alpha's Relationship With Skeletal Muscle Palmitate Oxidation Is Not Present With Obesity Despite Maintained PGC-1alpha and PGC-1beta Protein." American Journal of Physiology. Endocrinology and Metabolism, vol. 294, no. 6, 2008, pp. E1060-9.
Holloway GP, Perry CG, Thrush AB, et al. PGC-1alpha's relationship with skeletal muscle palmitate oxidation is not present with obesity despite maintained PGC-1alpha and PGC-1beta protein. Am J Physiol Endocrinol Metab. 2008;294(6):E1060-9.
Holloway, G. P., Perry, C. G., Thrush, A. B., Heigenhauser, G. J., Dyck, D. J., Bonen, A., & Spriet, L. L. (2008). PGC-1alpha's relationship with skeletal muscle palmitate oxidation is not present with obesity despite maintained PGC-1alpha and PGC-1beta protein. American Journal of Physiology. Endocrinology and Metabolism, 294(6), pp. E1060-9. doi:10.1152/ajpendo.00726.2007.
Holloway GP, et al. PGC-1alpha's Relationship With Skeletal Muscle Palmitate Oxidation Is Not Present With Obesity Despite Maintained PGC-1alpha and PGC-1beta Protein. Am J Physiol Endocrinol Metab. 2008;294(6):E1060-9. PubMed PMID: 18349111.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PGC-1alpha's relationship with skeletal muscle palmitate oxidation is not present with obesity despite maintained PGC-1alpha and PGC-1beta protein. AU - Holloway,Graham P, AU - Perry,Christopher G R, AU - Thrush,A Brianne, AU - Heigenhauser,George J F, AU - Dyck,David J, AU - Bonen,Arend, AU - Spriet,Lawrence L, Y1 - 2008/03/18/ PY - 2008/3/20/pubmed PY - 2008/7/23/medline PY - 2008/3/20/entrez SP - E1060 EP - 9 JF - American journal of physiology. Endocrinology and metabolism JO - Am. J. Physiol. Endocrinol. Metab. VL - 294 IS - 6 N2 - Reduced skeletal muscle mitochondrial content and fatty acid oxidation are associated with obesity and insulin resistance. Although the exact mechanisms remain elusive, this may result from impaired mitochondrial biogenesis or reductions in the mitochondrial reticulum network. Therefore, the purpose of this study was to determine whether the protein contents of various transcription factors, including PGC-1alpha and PGC-1beta and proteins associated with mitochondrial fusion events, were reduced in skeletal muscle of nine obese (BMI = 37.6 +/- 2.2 kg/m(-2)) compared with nine age-matched lean (BMI = 23.3 +/- 0.7 kg/m(-2)) women. The protein contents of PGC-1alpha, PGC-1beta, PPARalpha, and tFAM were not reduced with obesity. In contrast, PPARgamma was increased (+22%, P < 0.05) with obesity, and there was a trend toward an increase (+31%, P = 0.13) in PPARdelta/beta. In lean individuals, PGC-1alpha protein correlated with citrate synthase (CS; r = 0.67) and rates of palmitate oxidation (r = 0.87), whereas PGC-1beta correlated with PPARgamma (r = 0.90), PPARdelta/beta (r = 0.63), and cytochrome c oxidase IV (COX-IV; r = 0.63). In obese individuals, the relationship between PGC-1alpha and CS was maintained (r = 0.65); however, the associations between PGC-1alpha and palmitate oxidation (r = -0.38) and PGC-1beta with PPARgamma (r = 0.14), PPARdelta/beta (r = 0.21), and COX-IV (r = 0.01) were lost. In addition, mitofusin-1 (MFN-1), MFN-2, and dynamin-related protein-1 (DRP-1) total protein contents were not altered with obesity (P > 0.05). These data suggest that altered regulation, and not reductions in the protein contents of transcription factors, is associated with insulin resistance. Also, it does not appear that alterations in the proteins associated with mitochondrial network formation and degradation can account for the observed decrease in mitochondrial content. SN - 0193-1849 UR - https://www.unboundmedicine.com/medline/citation/18349111/PGC_1alpha's_relationship_with_skeletal_muscle_palmitate_oxidation_is_not_present_with_obesity_despite_maintained_PGC_1alpha_and_PGC_1beta_protein_ L2 - http://www.physiology.org/doi/full/10.1152/ajpendo.00726.2007?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -