Pleiotropic effects of proopiomelanocortin and VGF nerve growth factor inducible neuropeptides for the long-term regulation of energy balance

Seasonal rhythms in energy balance are well documented across temperate and equatorial zones animals. The long-term regulated changes in seasonal physiology consists of a rheostatic system that is essential to successful time annual cycles in reproduction, hibernation, torpor, and migration. Most animals use the annual change in photoperiod as a reliable and robust environmental cue to entrain endogenous (i.e. circannual) rhythms. Research over the past few decades has predominantly examined the role of first order neuroendocrine peptides for the rheostatic changes in energy balance. These anorexigenic and orexigenic neuropeptides in the arcuate nucleus include neuropeptide y (Npy), agouti-related peptide (Agrp), cocaine and amphetamine related transcript (Cart) and pro-opiomelanocortin (Pomc). Recent studies also indicate that VGF nerve growth factor inducible (Vgf) in the arcuate nucleus is involved in the seasonal regulation of energy balance. In situ hybridization, qPCR and RNA-sequencing studies have identified that Pomc expression across fish, avian and mammalian species, is a neuroendocrine marker that reflects seasonal energetic states. Here we highlight that long-term changes in arcuate Pomc and Vgf expression is conserved across species and may provide rheostatic regulation of seasonal energy balance. •Arcuate nucleus is a neuroendocrine substrate for long-term rhythms in energy balance.•POMC and VGF are neuroendocrine controllers of the rheostatic control of body mass.•Npy, Agrp and Cart only signal short-term homeostatic changes in body mass.•Seasonal models are essential for understanding long-term rhythms in energy balance.