CONICET | Buscador de Institutos y Recursos Humanos

The hormones leptin and ghrelin act in the brain to regulate body weight homeostasis in anopposite fashion. Some of leptin?s and ghrelin?s central targets overlap suggesting that theaction of these hormones may modulate the same neuronal populations to drive food intake and energy expenditure. The present study aimed to explore the neuroanatomical bases of leptin and ghrelin interactions in the central nervous system and the functional consequence of the lack of the ghrelin signaling on leptin sensitivity. Thus, we systematically mapped the distribution of leptin receptor- and ghrelin receptor-expressing neurons throughout the adult mouse brain using dual-label histochemistry techniques. In particular, we performed both in situ hybridization histochemistry for ghrelin receptor in transgenic mice expressing EYFP in leptin-receptor expressing neurons. We found that cells containing both ghrelin and leptin receptors are mainly located in the medial part of the hypothalamic arcuate nucleus (Arc). In contrast, co-expression of ghrelin receptor mRNA within EYFP-containing neurons was much less extensive elsewhere in the brain. To further assess the physiological consequence of the observed co-localization, we assessed the responses of mice lacking ghrelin receptor to the anorectic actions of leptin in several experimental conditions using ad-libitum fed, diet-induced obese and fasted mouse models. We found that deletion of the ghrelin receptor does not affect the sensitivity to exogenously administrated leptin. Thus, we conclude that ghrelin and leptin act largely on distinct neuronal populations and that ghrelin receptor deficiency does not affect sensitivity to the actions of leptin on the regulation of the body weight homeostasis.