Involvement of neuropeptide CART in the central effects of insulin on feeding and body weight

• Published in: Pharmacology, biochemistry and behavior Vol. 181; pp. 101 - 109
• Main Authors: Nakhate, Kartik T., Subhedar, Nishikant K., Kokare, Dadasaheb M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2019
• Subjects: Animals; Anorexia - chemically induced; Antibodies, Monoclonal - pharmacology; Body weight; Body Weight - drug effects; CART; Eating - drug effects; Feeding Behavior - drug effects; Food intake; Hypothalamus - drug effects; Hypothalamus - immunology; Immunohistochemistry; Insulin; Insulin - administration & dosage; Insulin - pharmacology; Male; Nerve Tissue Proteins - administration & dosage; Nerve Tissue Proteins - immunology; Nerve Tissue Proteins - pharmacology; Neuropeptides - administration & dosage; Neuropeptides - immunology; Neuropeptides - pharmacology; Photoperiod; Rats; Rats, Sprague-Dawley; Weight Loss - drug effects; Immunohistochemistry; Food intake; Insulin; Body weight; CART
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2019.05.001

While insulin secreted from pancreas plays a pivotal role in the control of glucose homeostasis, it also interacts with hypothalamic sites and negatively influences the energy balance. The present study was undertaken to reveal the functional interaction between cocaine- and amphetamine-regulated transcript (CART), a well-known anorexic peptide, and insulin within the framework of hypothalamus in the regulation of feeding behavior and body weight. Insulin was administered daily by intracerebroventricular (icv) route, alone or in combination with CART (icv) for a period of seven days. Immediately thereafter, preweighed food was offered to the animals at the commencement of the dark phase. The food intake and body weight were measured daily just prior to next injection. Furthermore, brains of insulin-treated rats were processed for the immunohistochemical analysis of CART-containing elements in the hypothalamus. Treatment with insulin (6 mU, icv) for a period of 7 days caused a significant decrease in food intake and body weight as compared to control. Concomitant administration of CART (0.5 μg, icv) potentiated insulin-induced anorexia and weight loss. Insulin administration resulted in a significant increase in CART immunoreactivity in the hypothalamic arcuate, paraventricular, dorsomedial and ventromedial nuclei. We suggest that increased CART contents in the hypothalamus may be causally linked with anorexia and weight loss induced by insulin. •Insulin treatment induced anorexia and weight loss in rats.•Pretreatment with neuropeptide CART potentiated the effects of insulin.•Insulin treatment increased CART immunoreactivity in the hypothalamus.•Hypothalamic CART mediates the effects of insulin on feeding behavior.