Endogenous Ligand for GPR120, Docosahexaenoic Acid, Exerts Benign Metabolic Effects on the Skeletal Muscles via AMP-activated Protein Kinase Pathway.
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(2+) was critical for DHA-mediated AMPK phosphorylation and glucose uptake. In addition, DHA stimulated GLUT4 translocation AMPK-dependently. Inhibition of AMPK and Ca(2+)/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(2+) 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.
['Kim|Nami|N|', 'Lee|Jung Ok|JO|', 'Lee|Hye Jeong|HJ|', 'Kim|Hyung Ip|HI|', 'Kim|Joong Kwan|JK|', 'Lee|Yong Woo|YW|', 'Lee|Soo Kyung|SK|', 'Kim|Su Jin|SJ|', 'Park|Sun Hwa|SH|', 'Kim|Hyeon Soo|HS|']
D000263:Adenylate Kinase D000818:Animals D002460:Cell Line D004281:Docosahexaenoic Acids D005947:Glucose D008024:Ligands D051379:Mice D018482:Muscle, Skeletal D010766:Phosphorylation D051381:Rats D043562:Receptors, G-Protein-Coupled
metabolism AMP-activated kinase (AMPK) diabetes glucose transport signal transduction