Effect of leptin administration versus re-feeding on hypothalamic neuropeptide gene expression in fasted male rats

• Published in: Canadian journal of physiology and pharmacology Vol. 82; no. 12; pp. 1128 - 1134
• Main Authors: McAlister, Edward D, Van Vugt, Dean A
• Format: Journal Article
• Language: English
• Published: Ottawa, Canada NRC Research Press 01.12.2004; National Research Council of Canada; Canadian Science Publishing NRC Research Press
• Subjects: Adipocytes; Animals; Appetite - physiology; Arcuate nucleus; Biological and medical sciences; Body Weight - physiology; Cell Count; Cocaine- and amphetamine-regulated transcript protein; Eating - physiology; Fasting; Fasting - physiology; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression - drug effects; Histochemistry; Hypothalamus; Hypothalamus - drug effects; Hypothalamus - physiology; In Situ Hybridization; Lateral Ventricles - physiology; Leptin - pharmacology; Leptin receptors; Male; Metabolism; Nerve Tissue Proteins - metabolism; Neuroendocrine system; Neurons; Neuropeptide Y; Neuropeptide Y - metabolism; Neuropeptides - biosynthesis; Neuropeptides - genetics; Nutritional status; Perfusion; Rats; RNA, Complementary - biosynthesis; RNA, Complementary - genetics; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Neuropeptide Y; Feeding behavior; Rat; Rodentia; Central nervous system; Neuroendocrine regulation; Hypothalamus; Gene expression; Neuropeptide; Encephalon; Feeding; Vertebrata; Mammalia; Leptin; Nutritional status
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/y04-122

Adipocytes are the primary source of circulating leptin. Leptin inhibits eating, increases metabolism, and stimulates the reproductive axis. Numerous hypothalamic neuropeptides have been implicated in leptin's behavioral and neuroendocrine effects, including neuropeptide Y (NPY) and cocaine- and amphetamine-regulated transcript (CART). The aim of this study was to investigate the physiological relevance of leptin's signaling of nutritional status by comparing the effects of leptin with the effects of re-feeding on fasting-induced changes in the expression of the long form of the leptin receptor (Ob-Rb), NPY, and CART. Adult male rats were fasted for 48 h and treated with either intra cere broventricular (i.c.v.) or subcutaneous (s.c.) leptin throughout the fast, or fed ad libitum for 24 h after terminating the fast. Expression of NPY, Ob-Rb, and CART mRNA in the arcuate nucleus (ARC) was determined by in situ hybridization histochemistry and compared with vehicle-treated fed or fasted controls. Fasting increased NPY and Ob-Rb expression and decreased CART expression in the ARC. Leptin (regardless of route) and re-feeding were equally effective in normalizing CART mRNA expression. A similar trend was observed with Ob-Rb expression. In contrast, neither re-feeding nor s.c. leptin reversed the increased expression of NPY that was induced by fasting. Only i.c.v. leptin was effective in this regard. Our results indicate leptin and re-feeding are equally effective in normalizing fasting-induced changes in CART and Ob-Rb expression, but less effective in normalizing NPY expression. These results suggest that leptin is the primary nutritional signal regulating CART and Ob-Rb expression in the ARC, and highlight potential differences between CART and NPY neuron sensitivity to leptin signaling.Key words: CART, leptin receptor, NPY, neuropeptide gene expression, fasting, refeeding, hypothalamus.