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      Nesfatin-1: role as possible new anti-obesity treatment

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          Abstract

          In this article, we review on the current concepts about Nesfatin-1 as a new anti-obesity treatment and evaluate the existing issues in the context of this knowledge and the available literature. The intent is to enable clinicians to know Nesfatin-1 as a new anti-obesity treatment and make rational decisions based on this perspective as possible clinical application. Future research should seek to clarify whether Nesfatin-1 would be beneficial in the management of obesity.

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          Nesfatin-1-regulated oxytocinergic signaling in the paraventricular nucleus causes anorexia through a leptin-independent melanocortin pathway.

          Yasuo Uchiyama, Masatomo Mori, Natsu Yoshida … (2009)
          The hypothalamic paraventricular nucleus (PVN) functions as a center to integrate various neuronal activities for regulating feeding behavior. Nesfatin-1, a recently discovered anorectic molecule, is localized in the PVN. However, the anorectic neural pathway of nesfatin-1 remains unknown. Here we show that central injection of nesfatin-1 activates the PVN and brain stem nucleus tractus solitarius (NTS). In the PVN, nesfatin-1 targets both magnocellular and parvocellular oxytocin neurons and nesfatin-1 neurons themselves and stimulates oxytocin release. Immunoelectron micrographs reveal nesfatin-1 specifically in the secretory vesicles of PVN neurons, and immunoneutralization against endogenous nesfatin-1 suppresses oxytocin release in the PVN, suggesting paracrine/autocrine actions of nesfatin-1. Nesfatin-1-induced anorexia is abolished by an oxytocin receptor antagonist. Moreover, oxytocin terminals are closely associated with and oxytocin activates pro-opiomelanocortin neurons in the NTS. Oxytocin induces melanocortin-dependent anorexia in leptin-resistant Zucker-fatty rats. The present results reveal the nesfatin-1-operative oxytocinergic signaling in the PVN that triggers leptin-independent melanocortin-mediated anorexia.
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            Central nesfatin-1 reduces dark-phase food intake and gastric emptying in rats: differential role of corticotropin-releasing factor2 receptor.

            Yvette Taché, Miriam Goebel-Stengel, Lixin Wang … (2009)
            Nesfatin-1, derived from nucleobindin2, is expressed in the hypothalamus and reported in one study to reduce food intake (FI) in rats. To characterize the central anorexigenic action of nesfatin-1 and whether gastric emptying (GE) is altered, we injected nesfatin-1 into the lateral brain ventricle (intracerebroventricular, icv) or fourth ventricle (4v) in chronically cannulated rats or into the cisterna magna (intracisternal, ic) under short anesthesia and compared with ip injection. Nesfatin-1 (0.05 microg/rat, icv) decreased 2-3 h and 3-6 h dark-phase FI by 87 and 45%, respectively, whereas ip administration (2 microg/rat) had no effect. The corticotropin-releasing factor (CRF)(1)/CRF(2) antagonist astressin-B or the CRF(2) antagonist astressin(2)-B abolished icv nesfatin-1's anorexigenic action, whereas an astressin(2)-B analog, devoid of CRF-receptor binding affinity, did not. Nesfatin-1 icv induced a dose-dependent reduction of GE by 26 and 43% that was not modified by icv astressin(2)-B. Nesfatin-1 into the 4v (0.05 microg/rat) or ic (0.5 microg/rat) decreased cumulative dark-phase FI by 29 and 60% at 1 h and by 41 and 37% between 3 and 5 h, respectively. This effect was neither altered by ic astressin(2)-B nor associated with changes in GE. Cholecystokinin (ip) induced Fos expression in 43% of nesfatin-1 neurons in the paraventricular hypothalamic nucleus and 24% of those in the nucleus tractus solitarius. These data indicate that nesfatin-1 acts centrally to reduce dark phase FI through CRF(2)-receptor-dependent pathways after forebrain injection and CRF(2)-receptor-independent pathways after hindbrain injection. Activation of nesfatin-1 neurons by cholecystokinin at sites regulating food intake may suggest a role in gut peptide satiation effect.
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              Nesfatin-1 exerts long-term effect on food intake and body temperature.

              K Könczöl, O Pintér, S Ferenczi … (2012)
              To determine whether the anorexigenic peptide, nesfatin-1 affects energy expenditure, and to follow the time course of its effects.
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                Author and article information

                Journal
                Journal ID (nlm-ta): EXCLI J
                Journal ID (iso-abbrev): EXCLI J
                Journal ID (publisher-id): EXCLI J
                Title: EXCLI Journal
                Publisher: Leibniz Research Centre for Working Environment and Human Factors
                ISSN (Electronic): 1611-2156
                Publication date (Electronic): 26 May 2014
                Publication date Collection: 2014
                Volume: 13
                Pages: 586-591
                Affiliations
                [1 ]Center of Obesity and Eating Disorders, Stella Maris Mediterraneum Foundation, Chiaromonte, Potenza, Italy
                [2 ]Department of Science, University of Basilicata, Potenza, Viale dell'Ateneo Lucano, 10, 85100, Italy
                [3 ]Unit of Surgery, S. Giovanni Hospital - Lagonegro, Potenza, Italy
                [4 ]National Cancer Institute "Pascale Foundation" - IRCS- 83013 Mercogliano (Av), Italy
                Author notes
                *To whom correspondence should be addressed: Carmine Finelli, Center of Obesity and Eating Disorders, Stella Maris Mediterraneum Foundation, Chiaromonte, Potenza, Italy, E-mail: carminefinelli74@ 123456yahoo.it
                Article
                Publisher ID: 2014-288 Publisher ID: Doc586
                PMC ID: 4464156
                SO-VID: 138e31c1-eb32-4d0d-9920-da873a46841e
                Copyright © Copyright © 2014 Finelli et al.
                License:

                This is an Open Access article distributed under the following Assignment of Rights http://www.excli.de/documents/assignment_of_rights.pdf. You are free to copy, distribute and transmit the work, provided the original author and source are credited.

                History
                Date received : 02 April 2014
                Date accepted : 08 May 2014
                Categories
                Subject: Review Article

                Keywords: nesfatin-1,obesity,drug treatment
                Data availability:
                Keywords: nesfatin-1, obesity, drug treatment

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