title: Peripheral effect of alpha-melanocyte-stimulating hormone on fatty acid oxidation in skeletal muscle.
abstract: To study the peripheral effects of melanocortin on fuel homeostasis in skeletal muscle, we assessed palmitate oxidation and AMP kinase activity in alpha-melanocyte-stimulating hormone (alpha-MSH)-treated muscle cells. After alpha-MSH treatment, carnitine palmitoyltransferase-1 and fatty acid oxidation (FAO) increased in a dose-dependent manner. A strong melanocortin agonist, NDP-MSH, also stimulated FAO in primary culture muscle cells and C2C12 cells. However, [Glu6]alpha-MSH-ND, which has ample MC4R and MC3R agonistic activity, stimulated FAO only at high concentrations (10(-5) M). JKC-363, a selective MC4R antagonist, did not suppress alpha-MSH-induced FAO. Meanwhile, SHU9119, which has both antagonistic activity on MC3R and MC4R and agonistic activity on both MC1R and MC5R, increased the effect of alpha-MSH on FAO in both C2C12 and primary muscle cells. Small interference RNA against MC5R suppressed the alpha-MSH-induced FAO effectively. cAMP analogues mimicked the effect of alpha-MSH on FAO, and the effects of both alpha-MSH and cAMP analogue-mediated FAO were antagonized by a protein kinase A inhibitor (H89) and a cAMP antagonist ((Rp)-cAMP). Acetyl-CoA carboxylase activity was suppressed by alpha-MSH and cAMP analogues by phosphorylation through AMP-activated protein kinase activation in C2C12 cells. Taken together, these results suggest that alpha-MSH increases FAO in skeletal muscle, in which MC5R may play a major role. Furthermore, these results suggest that alpha-MSH-induced FAO involves cAMP-protein kinase A-mediated AMP-activated protein kinase activation.
authors.affiliation: Department of Internal Medicine & Endocrine Research Institute, Yonsei University College of Medicine, 134 Shinchon-Dong, Seodaemoon-Gu, Seoul 120-752, Korea.
authors.forename: Juan Ji
authors.initials: JJ
authors.lastname: An
authors.forename: Yumie
authors.initials: Y
authors.lastname: Rhee
authors.forename: Se Hwa
authors.initials: SH
authors.lastname: Kim
authors.forename: Dol Mi
authors.initials: DM
authors.lastname: Kim
authors.forename: Dong-He
authors.initials: DH
authors.lastname: Han
authors.forename: Jung Hee
authors.initials: JH
authors.lastname: Hwang
authors.forename: Young-Jun
authors.initials: YJ
authors.lastname: Jin
authors.forename: Bong Soo
authors.initials: BS
authors.lastname: Cha
authors.forename: Ja-Hyun
authors.initials: JH
authors.lastname: Baik
authors.forename: Won Tae
authors.initials: WT
authors.lastname: Lee
authors.forename: Sung-Kil
authors.initials: SK
authors.lastname: Lim
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D017931:DNA Primers; D005227:Fatty Acids / Q000378:metabolism*; D006614:Hindlimb; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008931:Mitochondria, Muscle / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000521:alpha-MSH / Q000494:pharmacology*
chemical_list: D017931:DNA Primers; D005227:Fatty Acids; D044102:Receptor, Melanocortin, Type 1; D011994:Recombinant Proteins; D000521:alpha-MSH