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 journalArticlepeer-review

29 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 Ca2+ was critical for DHA-mediated AMPK phosphorylation and glucose uptake. In addition, DHA stimulated GLUT4 translocation AMPK-dependently. Inhibition of AMPK and Ca2+/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 Ca2+ 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
  • Molecular Biology
  • Cell Biology

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