GPR119 regulates genetic markers of fatty acid oxidation in cultured skeletal muscle myotubes

L M Cornall, M L Mathai, D H Hryciw, A C Simcocks, Paul Edmond O'Brien, John Wentworth, A J McAinch

Research output: Contribution to journalArticleResearchpeer-review

13 Citations (Scopus)

Abstract

Gene knockout and agonist studies indicate that activation of the G protein-coupled receptor, GPR119, protects against diet-induced obesity and insulin resistance. It is not known if GPR119 activation in skeletal muscle mediates these effects. To address this uncertainty, we measured GPR119 expression in skeletal muscle and determined the effects of PSN632408, a GPR119 agonist, on the expression of genes and proteins required for fatty acid and glucose oxidation in cultured myotubes. GPR119 expression was readily detected in rat skeletal muscle and mRNAs were induced by 12 weeks of high-fat feeding. Treatment of cultured mouse C2C12 myotubes with 5 I?M PSN632408 or 0.5 mM palmitate reduced expression of mRNAs encoding fatty acid oxidation genes to similar extents. More so, treatment with PSN632408 decreased AMPKI? (Thr172 phosphorylation) activity in the absence of palmitate and ACC (Ser79 phosphorylation) activity in the presence of palmitate. In human primary myotubes PSN632408 decreased expression of PDK4 and AMPKI?2 mRNA in myotubes derived from obese donors. These data suggest GPR119 activation in skeletal muscle may impair fatty acid and glucose oxidation.
Original languageEnglish
Pages (from-to)108 - 118
Number of pages11
JournalMolecular and Cellular Endocrinology
Volume365
Issue number1
DOIs
Publication statusPublished - 2013

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