Epinephrine and AICAR-induced PGC-1α mRNA expression is intact in skeletal muscle from rats fed a high-fat diet
Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a master regulator of mitochondrial biogenesis and is controlled, at least in part, through AMP-activated protein kinase and p38-dependent pathways. There is evidence demonstrating that activation of these kinases and induction...
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Veröffentlicht in: | American Journal of Physiology: Cell Physiology 2012-06, Vol.302 (12), p.C1772-C1779 |
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Zusammenfassung: | Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a master regulator of mitochondrial biogenesis and is controlled, at least in part, through AMP-activated protein kinase and p38-dependent pathways. There is evidence demonstrating that activation of these kinases and induction of PGC-1α in skeletal muscle are regulated by catecholamines. The purpose of the present study was to determine if consumption of a high-fat diet (HFD) impairs epinephrine and 5-aminoimidazole-4-carboxamide-1β-d-ribofuranoside (AICAR) signaling and induction of PGC-1α in rat skeletal muscle. Male Wistar rats were fed chow or a HFD for 6 wk and then given a weight-adjusted bolus injection of epinephrine (20, 10, or 5 μg/100 g body wt sc) or saline, and triceps muscles were harvested 30 min (signaling) or 2 and 4 h (gene expression) postinjection. Despite blunted increases in p38 phosphorylation, the ability of epinephrine to induce PGC-1α was intact in skeletal muscle from HFD-fed rats and was associated with normal increases in activation of PKA and phosphorylation of cAMP response element-binding protein, reputed mediators of PGC-1α expression. The attenuated epinephrine-mediated increase in p38 phosphorylation was independent of increases in MAPK phosphatase 1. At 2 h following AICAR treatment (0.5 g/kg body wt sc), AMP-activated protein kinase and acetyl-CoA carboxylase phosphorylation were similar in skeletal muscle from chow- and HFD-fed rats. Surprisingly, AICAR-induced increases in PGC-1α mRNA levels were greater in skeletal muscle from HFD-fed rats. Our results demonstrate that the ability of epinephrine and AICAR to induce PGC-1α remains intact in skeletal muscle from HFD-fed rats. These results question the existence of reduced β-adrenergic responsiveness in diet-induced obesity and demonstrate that increases in p38 phosphorylation are not required for induction of PGC-1α in muscle from obese rats. |
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ISSN: | 0363-6143 1522-1563 |
DOI: | 10.1152/ajpcell.00410.2011 |