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 a 28 amino acid peptide hormone that targets the brain to promote feeding and adiposity.The ghrelin receptor, the GHSR1a, is expressed within hypothalamic nuclei, including the DMH and PMV, but the role of GHSR1a signaling in these regions is unknown.In order to investigate whether GHSR1a signaling within these regions modulates energy balance, we conducted two experiments.In study 1, we attached a minipump filled with saline, ghrelin, or a GHSR1a antagonist to a cannula aimed at the DMH in adult male C57BLJ6 mice and assessed their metabolic profile.In study 2, we employed similar drug treatments as in study 1, but aimed the cannula at the PMV.We found that chronic stimulation of the GHSR1a in the DMH leads to an increase in body weight, primarily in the form of adipose tissue, without affecting caloric intake.The increase in body fat is accompanied by and may be due to a decrease in energy expenditure, which is not associated with a decrease in locomotor activity.Further, chronic stimulation of the GHSR1a in the PMV as well as the DMH slows glucose clearance.However, infusion of ghrelin into the PMV promotes the oxidation of carbohydrates as a fuel source, without affecting food intake, body weight, or body fat.This suggests that GHSR signaling has distinct roles in the DMH and PMV in maintaining energy homeostasis.