Journal article
PGC-1α regulation by exercise training and its influences on muscle function and insulin sensitivity
American journal of physiology: endocrinology and metabolism, Vol.299(2), pp.E145-E161
08/01/2010
DOI: 10.1152/ajpendo.00755.2009
PMCID: PMC2928513
PMID: 20371735
Abstract
The peroxisome proliferator-activated receptor-gamma (PPARgamma) coactivator-1alpha (PGC-1alpha) is a major regulator of exercise-induced phenotypic adaptation and substrate utilization. We provide an overview of 1) the role of PGC-1alpha in exercise-mediated muscle adaptation and 2) the possible insulin-sensitizing role of PGC-1alpha. To these ends, the following questions are addressed. 1) How is PGC-1alpha regulated, 2) what adaptations are indeed dependent on PGC-1alpha action, 3) is PGC-1alpha altered in insulin resistance, and 4) are PGC-1alpha-knockout and -transgenic mice suitable models for examining therapeutic potential of this coactivator? In skeletal muscle, an orchestrated signaling network, including Ca(2+)-dependent pathways, reactive oxygen species (ROS), nitric oxide (NO), AMP-dependent protein kinase (AMPK), and p38 MAPK, is involved in the control of contractile protein expression, angiogenesis, mitochondrial biogenesis, and other adaptations. However, the p38gamma MAPK/PGC-1alpha regulatory axis has been confirmed to be required for exercise-induced angiogenesis and mitochondrial biogenesis but not for fiber type transformation. With respect to a potential insulin-sensitizing role of PGC-1alpha, human studies on type 2 diabetes suggest that PGC-1alpha and its target genes are only modestly downregulated (< or =34%). However, studies in PGC-1alpha-knockout or PGC-1alpha-transgenic mice have provided unexpected anomalies, which appear to suggest that PGC-1alpha does not have an insulin-sensitizing role. In contrast, a modest ( approximately 25%) upregulation of PGC-1alpha, within physiological limits, does improve mitochondrial biogenesis, fatty acid oxidation, and insulin sensitivity in healthy and insulin-resistant skeletal muscle. Taken altogether, there is substantial evidence that the p38gamma MAPK-PGC-1alpha regulatory axis is critical for exercise-induced metabolic adaptations in skeletal muscle, and strategies that upregulate PGC-1alpha, within physiological limits, have revealed its insulin-sensitizing effects.
Details
- Title: Subtitle
- PGC-1α regulation by exercise training and its influences on muscle function and insulin sensitivity
- Creators
- Vitor A Lira - University of VirginiaCarley R Benton - University of GuelphZhen Yan - University of VirginiaArend Bonen - University of Guelph
- Resource Type
- Journal article
- Publication Details
- American journal of physiology: endocrinology and metabolism, Vol.299(2), pp.E145-E161
- DOI
- 10.1152/ajpendo.00755.2009
- PMID
- 20371735
- PMCID
- PMC2928513
- NLM abbreviation
- Am J Physiol Endocrinol Metab
- eISSN
- 1522-1555
- Grant note
- Canadian Institutes of Health Research R01 AR050429 / NIAMS NIH HHS R01-AR-050429 / NIAMS NIH HHS
- Language
- English
- Date published
- 08/01/2010
- Academic Unit
- Health, Sport, and Human Physiology
- Record Identifier
- 9984267257202771
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