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

Juan Ji An, Yumie Rhee, Hwa Kim Se, Mi Kim Dol, Dong He Han, Hee Hwang Jung, Young Jun Jin, Soo Cha Bong, Ja Hyun Baik, Tae Lee Won, Sungkil Lim

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)2862-2870
Number of pages9
JournalJournal of Biological Chemistry
Volume282
Issue number5
DOIs
Publication statusPublished - 2007 Jan 2

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Melanocyte-Stimulating Hormones
Muscle
Skeletal Muscle
Fatty Acids
Oxidation
Melanocortins
Muscle Cells
AMP-Activated Protein Kinases
Cells
Cyclic AMP-Dependent Protein Kinases
Chemical activation
Carnitine O-Palmitoyltransferase
Acetyl-CoA Carboxylase
Adenylate Kinase
Phosphorylation
Palmitates
Corrosion inhibitors
Protein Kinase Inhibitors
RNA Interference
Cell culture

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

An, Juan Ji ; Rhee, Yumie ; Se, Hwa Kim ; Dol, Mi Kim ; Han, Dong He ; Jung, Hee Hwang ; Jin, Young Jun ; Bong, Soo Cha ; Baik, Ja Hyun ; Won, Tae Lee ; Lim, Sungkil. / Peripheral effect of α-melanocyte-stimulating hormone on fatty acid oxidation in skeletal muscle. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 5. pp. 2862-2870.
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title = "Peripheral effect of α-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 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.",
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An, JJ, Rhee, Y, Se, HK, Dol, MK, Han, DH, Jung, HH, Jin, YJ, Bong, SC, Baik, JH, Won, TL & Lim, S 2007, 'Peripheral effect of α-melanocyte-stimulating hormone on fatty acid oxidation in skeletal muscle', Journal of Biological Chemistry, vol. 282, no. 5, pp. 2862-2870. https://doi.org/10.1074/jbc.M603454200

Peripheral effect of α-melanocyte-stimulating hormone on fatty acid oxidation in skeletal muscle. / An, Juan Ji; Rhee, Yumie; Se, Hwa Kim; Dol, Mi Kim; Han, Dong He; Jung, Hee Hwang; Jin, Young Jun; Bong, Soo Cha; Baik, Ja Hyun; Won, Tae Lee; Lim, Sungkil.

In: Journal of Biological Chemistry, Vol. 282, No. 5, 02.01.2007, p. 2862-2870.

Research output: Contribution to journalArticle

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, Sungkil

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.

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