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Endogenous Ligand for GPR120, Docosahexaenoic Acid, Exerts Benign Metabolic Effects on the Skeletal Muscles via AMP-activated Protein Kinase Pathway

Authors
Kim, NamiLee, Jung OkLee, Hye JeongKim, Hyung IpKim, Joong KwanLee, Yong WooLee, Soo KyungKim, Su JinPark, Sun HwaKim, Hyeon Soo
Issue Date
14-8월-2015
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Citation
JOURNAL OF BIOLOGICAL CHEMISTRY, v.290, no.33, pp.20438 - 20447
Indexed
SCIE
SCOPUS
Journal Title
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume
290
Number
33
Start Page
20438
End Page
20447
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/92760
DOI
10.1074/jbc.M115.657379
ISSN
0021-9258
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.
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