Endogenous ligand for GPR120, docosahexaenoic acid, exerts benign metabolic effects on the skeletal muscles via AMP-activated protein kinase pathway

Nami Kim, Jung Ok Lee, Hye Jeong Lee, Hyung Ip Kim, Joong Kwan Kim, Yong Woo Lee, Soo Kyung Lee, Su Jin Kim, Sun-Hwa Park, Hyeon Soo Kim

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Docosahexaenoic acid (DHA) is an endogenous ligand of G protein-coupled receptor 120 (GPR120). However, the mechanisms underlying DHA action are poorly understood. In this study, DHA stimulated glucose uptake in the skeletal muscles in an AMP-activated protein kinase (AMPK)-dependent manner. GPR120-mediated increase in intracellular Ca<sup>2+</sup> was critical for DHA-mediated AMPK phosphorylation and glucose uptake. In addition, DHA stimulated GLUT4 translocation AMPK-dependently. Inhibition of AMPK and Ca<sup>2+</sup>/calmodulin-dependent protein kinase kinase blocked DHA-induced glucose uptake. DHA and GW9508, a GPR120 agonist, increased GPR120 expression. DHA-mediated glucose uptake was not observed in GPR120 knockdown conditions. DHA increased AMPK phosphorylation, glucose uptake, and intracellular Ca<sup>2+</sup> concentration in primary cultured myoblasts. Taken together, these results indicated that the beneficial metabolic role of DHA was attributed to its ability to regulate glucose via the GPR120-mediated AMPK pathway in the skeletal muscles.

Original languageEnglish
Pages (from-to)20438-20447
Number of pages10
JournalJournal of Biological Chemistry
Volume290
Issue number33
DOIs
Publication statusPublished - 2015 Aug 14

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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