Intracerebroventricular melanin-concentrating hormone stimulates food intake in sheep

Abstract

Melanin-concentrating hormone (MCH) stimulates feeding when injected intracerebroventricularly (ICV) in rats. At present it is not clear whether the function of MCH is similar in ruminants, which are species with a continuous delivery of nutrients. Therefore the current investigation sought to determine the role of MCH in sheep. In the first experiment, six, castrate male sheep were satiated and received one of four treatments [saline, 0.1, or 1.0 nmol/kg MCH, and NPY (0.1 nmol/kg)] injected ICV over 30s, then infused ICV for 6 h ( approximately 500 microl/h). Food intake was measured for 2 h before and at 2, 4, 6, 8, 12 and 24 h. In this experiment, feed intake was increased (P<or=0.05) in NPY treated sheep only. In the second experiment, the same sheep were fed to satiety and then randomized to receive one of six treatments [saline and either 0.1, 1.0 or 5.0 nmol/kg MCH, 0.1 nmol/kg NPY, or MCH+NPY (0.1 nmol/kg)] injected ICV over 30 s. Food intake was measured for 2 h before and at 2, 4, 6, 8, 12, and 24 h after ICV injection. All doses of MCH as well as NPY resulted in greater (P<or=0.05) food intake than saline. In order to determine whether MCH expression was regulated by fasting, brains from fed and 3-day fasted sheep were fixed in situ, sectioned in the coronal plane, and subjected to dual-label immunohistochemistry using Fos as a marker for neuronal activity. Nutritional state (fed or fasted) did not alter Fos expression in MCH neurons. Finally, using real time PCR, MCH mRNA was unchanged by fasting. In this study we found bolus ICV MCH to be a potent stimulus to food intake in sheep, but MCH was not regulated by fasting.