title: Endogenous Ligand for GPR120, Docosahexaenoic Acid, Exerts Benign Metabolic Effects on the Skeletal Muscles via AMP-activated Protein Kinase Pathway.
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(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.
authors.affiliation: From the Department of Anatomy, Korea University College of Medicine, Seoul 136-701, Korea.
authors.forename: Nami
authors.initials: N
authors.lastname: Kim
authors.affiliation: From the Department of Anatomy, Korea University College of Medicine, Seoul 136-701, Korea.
authors.forename: Jung Ok
authors.initials: JO
authors.lastname: Lee
authors.affiliation: From the Department of Anatomy, Korea University College of Medicine, Seoul 136-701, Korea.
authors.forename: Hye Jeong
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: From the Department of Anatomy, Korea University College of Medicine, Seoul 136-701, Korea.
authors.forename: Hyung Ip
authors.initials: HI
authors.lastname: Kim
authors.affiliation: From the Department of Anatomy, Korea University College of Medicine, Seoul 136-701, Korea.
authors.forename: Joong Kwan
authors.initials: JK
authors.lastname: Kim
authors.affiliation: From the Department of Anatomy, Korea University College of Medicine, Seoul 136-701, Korea.
authors.forename: Yong Woo
authors.initials: YW
authors.lastname: Lee
authors.affiliation: From the Department of Anatomy, Korea University College of Medicine, Seoul 136-701, Korea.
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Lee
authors.affiliation: From the Department of Anatomy, Korea University College of Medicine, Seoul 136-701, Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: From the Department of Anatomy, Korea University College of Medicine, Seoul 136-701, Korea.
authors.forename: Sun Hwa
authors.initials: SH
authors.lastname: Park
authors.affiliation: From the Department of Anatomy, Korea University College of Medicine, Seoul 136-701, Korea anatomykim@korea.ac.kr.
authors.forename: Hyeon Soo
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D008024:Ligands; D051379:Mice; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*
chemical_list: C498007:FFAR4 protein, mouse; C533284:Ffar4 protein, rat; D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D004281:Docosahexaenoic Acids; D000263:Adenylate Kinase; D005947:Glucose
keywords: AMP-activated kinase (AMPK); diabetes; glucose transport; metabolism; signal transduction