title: Nesfatin-130-59 Injected Intracerebroventricularly Differentially Affects Food Intake Microstructure in Rats Under Normal Weight and Diet-Induced Obese Conditions.
abstract: Nesfatin-1 is well-established to induce an anorexigenic effect. Recently, nesfatin-130-59, was identified as active core of full length nesfatin-11-82 in mice, while its role in rats remains unclear. Therefore, we investigated the effects of nesfatin-130-59 injected intracerebroventricularly (icv) on the food intake microstructure in rats. To assess whether the effect was also mediated peripherally we injected nesfatin-130-59 intraperitoneally (ip). Since obesity affects the signaling of various food intake-regulatory peptides we investigated the effects of nesfatin-130-59 under conditions of diet-induced obesity (DIO). Male Sprague-Dawley rats fed ad libitum with standard diet were icv cannulated and injected with vehicle (5 μl ddH2O) or nesfatin-130-59 at 0.37, 1.1, and 3.3 μg (0.1, 0.3, 0.9 nmol/rat) and the food intake microstructure assessed using a food intake monitoring system. Next, naïve rats were injected ip with vehicle (300 μl saline) or nesfatin-130-59 (8.1, 24.3, 72.9 nmol/kg). Lastly, rats were fed a high fat diet for 10 weeks and those developing DIO were icv cannulated. Nesfatin-1 (0.9 nmol/rat) or vehicle (5 μl ddH2O) was injected icv and the food intake microstructure assessed. In rats fed standard diet, nesfatin-130-59 caused a dose-dependent reduction of dark phase food intake reaching significance at 0.9 nmol/rat in the period of 4-8 h post injection (-29%) with the strongest reduction during the fifth hour (-75%), an effect detectable for 24 h (-12%, p < 0.05 vs. vehicle). The anorexigenic effect of nesfatin-130-59 was due to a reduction in meal size (-44%, p < 0.05), while meal frequency was not altered compared to vehicle. In contrast to icv injection, nesfatin-130-59 injected ip in up to 30-fold higher doses did not alter food intake. In DIO rats fed high fat diet, nesfatin-130-59 injected icv reduced food intake in the third hour post injection (-71%), an effect due to a reduced meal frequency (-27%, p < 0.05), while meal size was not altered. Taken together, nesfatin-130-59 is the active core of nesfatin-11-82 and acts centrally to reduce food intake in rats. The anorexigenic effect depends on the metabolic condition with increased satiation (reduction in meal size) under normal weight conditions, while in DIO rats satiety (reduction in meal frequency) is induced.
authors.affiliation: Division of General Internal and Psychosomatic Medicine, Charité Center for Internal Medicine and Dermatology, Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Philip
authors.initials: P
authors.lastname: Prinz
authors.affiliation: Division of General Internal and Psychosomatic Medicine, Charité Center for Internal Medicine and Dermatology, Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Pauline
authors.initials: P
authors.lastname: Teuffel
authors.affiliation: Division of General Internal and Psychosomatic Medicine, Charité Center for Internal Medicine and Dermatology, Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Lembke
authors.affiliation: Division of General Internal and Psychosomatic Medicine, Charité Center for Internal Medicine and Dermatology, Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kobelt
authors.affiliation: Department of Internal Medicine and Institute of Neurogastroenterology, Martin-Luther-Krankenhaus Berlin, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Goebel-Stengel
authors.affiliation: Division of General Internal and Psychosomatic Medicine, Charité Center for Internal Medicine and Dermatology, Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Hofmann
authors.affiliation: Division of General Internal and Psychosomatic Medicine, Charité Center for Internal Medicine and Dermatology, Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Rose
authors.affiliation: Division of General Internal and Psychosomatic Medicine, Charité Center for Internal Medicine and Dermatology, Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Burghard F
authors.initials: BF
authors.lastname: Klapp
authors.affiliation: Division of General Internal and Psychosomatic Medicine, Charité Center for Internal Medicine and Dermatology, Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Stengel
keywords: NUCB2; anorexigenic; brain-gut-axis; satiation; satiety