Metabolic effects of ghrelin delivery into the hypothalamic ventral premammilary nucleus of male mice.

Ghrelin is a 28 amino acid peptide hormone that targets the brain to promote feeding and adiposity. The ghrowth hormone secretagogue receptor 1a (GHSR1a) is expressed within many hypothalamic nuclei, including the ventral premammillary nucleus (PMV), but the role of GHSR1a signaling in this region is unknown. In order to investigate whether GHSR1a signaling within the PMV modulates energy balance, we implanted osmotic minipumps connected to cannulae that were implanted intracranially and aiming at the PMV. The cannulae delivered either saline or ghrelin (10 µg/day at a flow rate of 0.11µL/h for 28 days) into the PMV of adult male C57BLJ6 mice. We found that chronic infusion of ghrelin into the PMV increased weight gain, promoted the oxidation of carbohydrates as a fuel source and resulted in hyperglycemia, without affecting food intake, or body fat. This suggests that ghrelin signaling in the PMV contributes to the modulation of metabolic fuel utilization and glucose homeostasis.

Ghrelin infused into the dorsomedial hypothalamus of male mice increases food intake and adiposity.

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 most hypothalamic nuclei, including the DMH, but the role of GHSR1a in this region on energy balance is unknown. In order to investigate whether GHSR1a within the DMH modulate energy balance, we implanted osmotic minipumps filled with saline, ghrelin, or the GHSR1a antagonist JMV2959, and connected it to a cannula aimed unilaterally at the DMH of adult male C57BLJ6 mice and assessed their metabolic profile. We found that chronic infusion of ghrelin in the DMH promoted an increase in caloric intake as well as a decrease in energy expenditure. This translated to an overall increase in weight gain, primarily in the form of adipose tissue in ghrelin treated animals. Further, chronic ghrelin unilateral infusion into the DMH slowed glucose clearance. These results suggest that GHSR in the DMH significantly contribute to the metabolic effects produced by ghrelin.