Endocrine Abstracts

Background/Aims: Food intake is orchestrated by complex neuronal networksresiding in the forebrain, hypothalamus, and brainstem, via orexigenic and anorexigenic neuropeptides. Nesfatin-1, the amino-terminal fragment of nucleobindin 2, is a potent anorexigenic and anti-obesogenic neuropeptide, with widespread central distribution in rodents. In obese humans, our research group has recently reported reduced nesfatin-1 protein expression in the lateral hypothalamic area, a brain structure involved in appetite and body weight regulation and connected with brainstem feeding centres. In spite of the wealth of data in animals, no information is available about nesfatin-1 localization in the human brainstem. The aim of the present study was to explore nesfatin-1 distribution pattern in human brainstem nuclei as well as the association between nesfatin-1 protein expression and body mass index.

Methods: For this purpose, human brainstemsections from 20 autopsy cases (13 males, seven females; 8 normal weight, 6 overweight, 6 obese) were examined using immunohistochemistry and double immunofluorescence labeling

Results: Intense nesfatin-1 immunoexpression was observed in various brainstem areas, including nuclei involved in energy homeostasis and in autonomic and behavioral functions, such as the nucleus of the solitary tract, dorsal motor nucleus of vagus, area postrema, inferior olive, reticular formation, raphe nuclei, locus coeruleus, parabrachial nuclei, and pontine nuclei, and in Purkinje cellsof the cerebellum. In addition, nesfatin-1 was extensively colocalized with neuropeptide Y and cocaine- and amphetamine-regulated transcript (peptides playing pivotal role in food intake and energy metabolism)in nucleus of the solitary tract, inferior olive, locus coeruleus, and dorsal raphe nucleus. Interestingly, nesfatin-1protein expression was significantly lower in obese than normal weight subjects in nucleus of the solitary tract (P < 0.05).

Conclusions: These findings provide for the first time neuroanatomical support for the potential role of nesfatin-1 in the human brainstem neuronal network controlling food intake and energy balance. In the nucleus of the solitary tract, an important hub of energy statusintegration and a neural substrate of food reward, altered neurochemistry such as nesfatin-1 deficiency may contribute to dysregulation of homeostatic and/or hedonic feeding behavior and thus to obesity.