Discovery of a bell-shaped dose response curve to melanin-concentrating hormone in the 3T3-L1 adipocyte model: low-dose MCH facilitates adipogenesis

Melanin-concentrating hormone signalling pathways in the central nervous system are of significant clinical interest in treating appetite, sleep, and mood disorders. However, with the additional discovery of active MCH signalling pathways in peripheral tissues, knowing the degree to which cellular context influence MCH receptor function is increasingly important. In this study, we discovered MCH-mediated signalling responses that demonstrated bell-shaped dose response curves in multiple assays using both pre- and post-adipocyte 3T3-L1 models. MCH facilitated cell adhesion in pre-adipocytes, increased both the number and size of lipid droplets and inhibited lipolysis in adipocytes, with a maximum effective dose at 1 nM MCH. We hypothesize that the concentration of MCH cells are exposed to influences G protein bias at MCHR1 and/or signal switching to an unidentified pathway. Furthermore, this study elucidates the importance of hormone concentration when measuring GPCR signalling pathways in cell culture and tissue models.