Effects of the central melanocortin system on feed intake, metabolic hormones and insulin action in the sheep.
This animal study investigated how the central nervous system melanocortin (CNS-MC) system influences feed intake, metabolic hormones, and insulin sensitivity in sheep. Ewes were surgically fitted with intracerebroventricular (ICV) cannulas and infused with artificial cerebrospinal fluid (aCSF), the α-MSH analog melanotan-I (MTI), or agouti-related peptide (AGRP) directly into the third ventricle. The study found that ICV MTI infusion significantly reduced voluntary feed intake, while AGRP infusion modestly increased it. MTI also elevated plasma triiodothyronine and thyroxine independently of changes in food intake, suggesting a direct central effect on thyroid hormone regulation. Notably, MTI did not affect plasma glucose, insulin, or cortisol under normal feeding conditions. However, during hyperinsulinemic-euglycemic clamp experiments in energy-restricted ewes, MTI impaired insulin's ability to suppress endogenous glucose production, indicating reduced hepatic insulin sensitivity. MTI also tended to lower plasma leptin in a feeding-level-dependent manner, with no effect on adiponectin. AGRP infusion did not significantly alter any measured plasma metabolic variables. The authors concluded that the CNS-MC system plays a role in regulating metabolic efficiency and peripheral insulin action in ruminants. Limitations include small sample sizes, a single non-human species, and the invasive ICV delivery route.