α-MSH and Foxc2 promote fatty acid oxidation through C/EBPβ negative transcription in mice adipose tissue.
Alpha melanocyte stimulating hormone (α-MSH) and Forkhead box C2 protein (Foxc2) enhance lipolysis in multiple tissues. However, their relationship in adipose fatty acid oxidation (FAO) remains unclear. Here, we demonstrated that α-MSH and Foxc2 increased palmitate oxidation to CO2in white (WAT) and brown adipose tissue (BAT). C/EBPβ expression was reduced by α-MSH and Foxc2. FFA level was elevated by α-MSH and pc-Foxc2 treatment along with increased FAO in white and brown adipocytes. The expression of FAO key enzymes, medium-chain acyl-CoA dehydrogenase (MCAD) and long-chain acyl-CoA dehydrogenase (LCAD) were increased in α-MSH and pc-Foxc2 group. Combination of α-MSH and Foxc2 treatment synergistically promoted FAO through increasing the activity of CPT-1 and phosphorylation of ACC. We found C/EBPβ bind to MC5R and Foxc2 promoter regions and inhibited FAO. cAMP level was increased by α-MSH and Foxc2 individually treated or combined treatment. Furthermore, cAMP/PKA pathway-specific inhibitor (H89) blocked the FAO, despite in α-MSH and Foxc2 both added group. While forskolin, the cAMP agonist, promoted FAO and enhanced the effect of α-MSH and Foxc2. Collectively, α-MSH and Foxc2 mutual promote FAO in WAT and BAT via cAMP/PKA signal pathway. And C/EBPβ as a transcription suppressor inhibits α-MSH and Foxc2 expression and FAO.
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
Lu
L
Gan
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
Zhenjiang
Z
Liu
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
Yizhe
Y
Chen
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
Dan Luo
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
Fei
F
Feng
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
Guannv
G
Liu
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
Chao
C
Sun
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D002478:Cells, Cultured; D005227:Fatty Acids / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D000521:alpha-MSH / Q000378:metabolism*
D022782:CCAAT-Enhancer-Binding Protein-beta; D005227:Fatty Acids; D051858:Forkhead Transcription Factors; C082078:mesenchyme fork head 1 protein; D000521:alpha-MSH