The Role of Growth Hormone Secretagogue Receptor (GHSR) Signaling in the Dorsomedial Hypothalamus (DMH) and Ventral Premammilary Nucleus (PMV) In Energy Homeostasis in Mice

Ghrelin is an orexigenic peptide hormone that acts on its receptor the GHSR1a within hypothalamic nuclei, including the DMH and PMV, but the role of GHSR1a signaling in these regions is unknown. To investigate this, in study 1, we attached a minipump filled with saline, ghrelin, or a GHSR1a antagonist to a cannula aimed at the DMH and assessed their metabolic profile. In study 2, we employed similar drug treatments as study 1, but aimed the cannula at the PMV. Chronic intra-DMH ghrelin increases body weight in the form of adipose tissue, without affecting caloric intake. This is accompanied by attenuated energy expenditure, and not locomotor activity. Infusions of ghrelin in the PMV and the DMH slows glucose clearance. Intra-PMV ghrelin promotes carbohydrate oxidation, without affecting food intake or body weight, suggesting that GHSR signaling has distinct roles in the DMH and PMV in energy homeostasis.