TY - JOUR
T1 - Peripheral effect of α-melanocyte-stimulating hormone on fatty acid oxidation in skeletal muscle
AU - An, Juan Ji
AU - Rhee, Yumie
AU - Se, Hwa Kim
AU - Dol, Mi Kim
AU - Han, Dong He
AU - Jung, Hee Hwang
AU - Jin, Young Jun
AU - Bong, Soo Cha
AU - Baik, Ja Hyun
AU - Won, Tae Lee
AU - Lim, Sung Kil
PY - 2007/1/2
Y1 - 2007/1/2
N2 - To study the peripheral effects of melanocortin on fuel homeostasis in skeletal muscle, we assessed palmitate oxidation and AMP kinase activity in α-melanocyte-stimulating hormone (α-MSH)-treated muscle cells. After α-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]α-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 α-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 α-MSH on FAO in both C2C12 and primary muscle cells. Small interference RNA against MC5R suppressed the α-MSH-induced FAO effectively. cAMP analogues mimicked the effect of α-MSH on FAO, and the effects of both α-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 α-MSH and cAMP analogues by phosphorylation through AMP-activated protein kinase activation in C2C12 cells. Taken together, these results suggest that α-MSH increases FAO in skeletal muscle, in which MC5R may play a major role. Furthermore, these results suggest that α-MSH-induced FAO involves cAMP-protein kinase A-mediated AMP-activated protein kinase activation.
AB - To study the peripheral effects of melanocortin on fuel homeostasis in skeletal muscle, we assessed palmitate oxidation and AMP kinase activity in α-melanocyte-stimulating hormone (α-MSH)-treated muscle cells. After α-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]α-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 α-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 α-MSH on FAO in both C2C12 and primary muscle cells. Small interference RNA against MC5R suppressed the α-MSH-induced FAO effectively. cAMP analogues mimicked the effect of α-MSH on FAO, and the effects of both α-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 α-MSH and cAMP analogues by phosphorylation through AMP-activated protein kinase activation in C2C12 cells. Taken together, these results suggest that α-MSH increases FAO in skeletal muscle, in which MC5R may play a major role. Furthermore, these results suggest that α-MSH-induced FAO involves cAMP-protein kinase A-mediated AMP-activated protein kinase activation.
UR - https://www.scopus.com/pages/publications/34047250799
U2 - 10.1074/jbc.M603454200
DO - 10.1074/jbc.M603454200
M3 - Article
C2 - 17127674
AN - SCOPUS:34047250799
SN - 0021-9258
VL - 282
SP - 2862
EP - 2870
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 5
ER -