Central nesfatin-1-expressing neurons are sensitive to peripheral inflammatory stimulus

During infection and inflammation, the immune, endocrine and nervous systems closely interact to coordinate a range of physiological and behavioral changes known as the acute phase reaction. The behavioral symptoms collectively referred to as "sickness behavior" include fever, anorexia, adipsia, lethargy and reduction in social interactions [1,2]. Cytokines peripherally released act on specific central nuclei involved in feeding and homeostatic regulation, which leads to the central component of the acute phase response. The complex neuronal circuitry involved in the coordinated response to inflammation, which includes notably the nucleus of the solitary tract (NTS), area postrema (AP), ventrolateral medulla, parabrachial nucleus, paraventricular hypothalamic nucleus (PVN), supraoptic nucleus (SON), arcuate nucleus (ARC) and central nucleus of the amygdala, has been identified mainly by quantification of the immediate-early gene c-fos [3,4]. The expression of the c-fos gene is widely considered to be a high resolution marker of neuronal activity, since a body of evidence demonstrates that Fos protein is expressed in neurons whose activity is strongly stimulated by synaptic input [5]. Used in combination with immunohistochemical determination of neuronal phenotype, this approach has led to the identification and location of neurons activated by inflammation and involved in the triggering of sickness behavior [6-8].Recently, Oh-I and co-authors reported the identification of a novel factor with anorexigenic properties, which they called nesfatin-1 [9]. Nesfatin-1 is reported to reduce food intake both after central (3rd ventricle) and peripheral administration [9,10]. Apart from adipose tissue, from which nesfatin-1 was first isolated, this protein is also expressed by gastric mucosa [11] and pancreatic β-cells [12]. This pattern of nesfatin-1 expression, as well as the presence of nesfatin-1 within the plasma of rodents and humans, strongly suggests that this compoun