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Peripheral effect of alpha-melanocyte-stimulating hormone on fatty acid oxidation in skeletal muscle

Authors
 Juan Ji An  ;  Yumie Rhee  ;  Sung-Kil Lim  ;  Won Tae Lee  ;  Ja-Hyun Baik  ;  Bong Soo Cha  ;  Young-Jun Jin  ;  Jung Hee Hwang  ;  Dong-He Han  ;  Dol Mi Kim  ;  Se Hwa Kim 
Citation
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.282(5) : 2862-2870, 2007 
Journal Title
 JOURNAL OF BIOLOGICAL CHEMISTRY 
ISSN
 0021-9258 
Issue Date
2007
MeSH
Animals ; Cells, Cultured ; DNA Primers ; Fatty Acids/metabolism* ; Hindlimb ; Kinetics ; Male ; Mice ; Mice, Inbred C57BL ; Mitochondria, Muscle/physiology ; Muscle, Skeletal/drug effects ; Muscle, Skeletal/embryology ; Muscle, Skeletal/metabolism* ; Myoblasts/drug effects ; Myoblasts/metabolism ; Oxidation-Reduction ; Receptor, Melanocortin, Type 1/genetics ; Receptor, Melanocortin, Type 1/physiology* ; Recombinant Proteins/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; alpha-MSH/pharmacology*
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.
Files in This Item:
T200705376.pdf Download
DOI
10.1074/jbc.M603454200
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Institute of Endocrinology (내분비연구소) > 1. Journal Papers
Yonsei Authors
Kim, Dol Mi(김똘미)
Kim, Se Hwa(김세화)
Rhee, Yumie(이유미) ORCID logo https://orcid.org/0000-0003-4227-5638
Lim, Sung Kil(임승길)
Cha, Bong Soo(차봉수) ORCID logo https://orcid.org/0000-0003-0542-2854
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/96228
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