Long-term alterations in adiposity affect the expression of melanin-concentrating hormone and enkephalin but not proopiomelanocortin in the hypothalamus of ovariectomized ewes

We have developed a ruminant model to study long-term alterations in adipos ity on the expression of appetite-regulating peptides in the hypothalamus. In this model endocrine and metabolic status are fully defined as well as b ody composition. The current study sought to define the effects of altered adiposity on the expression of genes for neuropeptide Y (NPY), POMC, enkeph alin (ENK), and melanin-concentrating hormone (MCH). Ovariectomized ewes wi th high (60 +/- 1 kg) (FAT) or low (37 +/- 3 kg) body weights (THIN) were b lood sampled every 10 min for 8 h to determine metabolic and endocrine stat us. The animals were then killed and the brains perfused for in situ hybrid ization. Body composition analysis was performed on the carcass using dual energy x-ray absorptiometry; this indicated that the FAT animals were 36 +/ - 1% fat, whereas the THIN animals were 15 +/- 2% fat. The LH interpulse in terval was lower and mean GH concentrations were higher in the THIN animals ; cortisol and TSH levels were not different between the two groups but fre e T-4 and free T-3 levels were lower; the FT3:FT4 ratio was higher in THIN ewes. Levels of insulin, lactate, and nonesterified fatty acids were lower in the THIN group, and plasma glucose and urea concentrations were similar in THIN and FAT animals. Levels of gene expression of NPY and MCH were high er in THIN ewes. POMC expression was similar in the two groups. In the THIN animals, ENK expression was lower in the paraventricular and ventromedial nuclei but higher in the periventricular region. In conclusion, we have sho wn that alterations in adiposity influence the expression of appetite-regul ating peptides in the absence of ovarian steroids. The appetite stimulators , NPY and MCH, appear to be involved in the metabolic response to altered a diposity, whereas ENK in the periventricular region may be linked to the se cretion of GH and possibly LH. Our results suggest that altered expression of appetite- regulating peptides can be linked with the endocrine and metab olic adaptations that occur with long-term changes in adiposity.