α-MSH and Foxc2 promote fatty acid oxidation through C/EBPβ negative transcription in mice adipose tissue

Alpha melanocyte stimulating hormone (alpha-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 alpha-MSH and Foxc2 increased palmitate oxidation to CO 2 in white (WAT) and brown adipose tissue (BAT). C/EBP beta expression was reduced by alpha-MSH and Foxc2. FFA level was elevated by alpha-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 alpha-MSH and pc-Foxc2 group. Combination of alpha-MSH and Foxc2 treatment synergistically promoted FAO through increasing the activity of CPT-1 and phosphorylation of ACC. We found C/EBP beta bind to MC5R and Foxc2 promoter regions and inhibited FAO. cAMP level was increased by alpha-MSH and Foxc2 individually treated or combined treatment. Furthermore, cAMP/PKA pathway-specific inhibitor (H89) blocked the FAO, despite in alpha-MSH and Foxc2 both added group. While forskolin, the cAMP agonist, promoted FAO and enhanced the effect of alpha-MSH and Foxc2. Collectively, alpha-MSH and Foxc2 mutual promote FAO in WAT and BAT via cAMP/PKA signal pathway. And C/EBP beta as a transcription suppressor inhibits alpha-MSH and Foxc2 expression and FAO.