Impaired hypothalamic CART expression in LHA and PVN nuclei of dehydration-induced anorexic rats

Abstract

Negative energy balance promotes physiological adaptations that ensure the survival of animals. Hypothalamic-pituitary-thyroid axis regulates basal energy expenditure and its down-regulating adaptation to negative energy balance is well described: in fasting, serum content of thyrotropin (TSH) and thyroid hormones (TH) decreases, enhancing survival odds of individuals. In contrast, dehydration-induced anorexic (DIA) rats present an impaired hypothalamic-pituitary-thyroid (HPT) axis adaptation despite their negative energy balance: increased circulating TSH levels. The implication of cocaine- and amphetamine-regulated transcript (CART), an anorexic peptide, in HPT axis function impairment and food-avoidance behavior displayed by DIA animals is unknown. Since CART is co-expressed with the peptide that regulates the HPT axis in hypophysiotropic paraventricular (PVN) neurons (thyrotropin-releasing hormone), we analyzed CART expression and possible implication on high TSH levels of DIA. We examined whether changes in CART expression from lateral hypothalamic area (LHA) and arcuate nucleus (ARC) could participate in food-avoidance of DIA rats. DIA and forced-food restricted (FFR) animals reduced their body weight and food intake. FFR rats had a down-regulation of their HPT axis (reduced serum TH and TSH content), whereas DIA animals had reduced TH but increased TSH levels. CART mRNA expression in ARC decreased similarly between experimental groups and diminished in anterior, medial PVN and in LHA of FFR but DIA showed unchanged levels. This impaired CART mRNA expression in anterior PVN and LHA could be related to the aberrant feeding behavior of DIA rats, but not to their deregulated HPT axis function.

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