title: Chronic delivery of α-melanocyte-stimulating hormone in rat hypothalamus using albumin-alginate microparticles: effects on food intake and body weight.
abstract: Chronic delivery of neuropeptides in the brain is a useful experimental approach to study their long-term effects on various biological parameters. In this work, we tested albumin-alginate microparticles, as a potential delivery system, to study if continuous release in the hypothalamus of α-melanocyte-stimulating hormone (α-MSH), an anorexigenic neuropeptide, may result in a long-term decrease in food intake and body weight. The 2-week release of α-MSH from peptide-loaded particles was confirmed by an in vitro assay. Then, daily food intake and body weight were studied for 18 days in rats injected bilaterally into the paraventricular hypothalamic nucleus with particles loaded or not with α-MSH. A decrease in body weight gain, persisting throughout the study, was found in rats injected with α-MSH-charged particles as compared with rats receiving non-charged particles and with rats injected with the same dose of α-MSH in solution. Food intake was significantly decreased for 3 days in rats receiving α-MSH-loaded particles and it was not followed by the feeding rebound effect which appears after food restriction. The presence of α-MSH-loaded particles in the hypothalamus was confirmed by immunohistochemistry. In conclusion, our study validates albumin-alginate microparticles as a new carrier system for long-term delivery of neuropeptides in the brain and demonstrates that chronic delivery of α-MSH in the hypothalamus results in a prolonged suppression of food intake and a decrease of body weight gain in rats.
authors: Inserm UMR1073, Nutrition, Gut and Brain Laboratory, Rouen 76183, France; Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, 76000, France.
authors: N
authors: N
authors: Lucas
authors: Inserm UMR1073, Nutrition, Gut and Brain Laboratory, Rouen 76183, France; Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, 76000, France.
authors: R
authors: R
authors: Legrand
authors: Inserm UMR1073, Nutrition, Gut and Brain Laboratory, Rouen 76183, France; Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, 76000, France.
authors: J
authors: J
authors: Breton
authors: Inserm UMR1073, Nutrition, Gut and Brain Laboratory, Rouen 76183, France; Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, 76000, France; Rouen University Hospital, CHU Charles Nicolle, Rouen 76183, France.
authors: P
authors: P
authors: Déchelotte
authors: Institute of Molecular Chemistry of Reims (ICMR), UMR CNRS 7312, University of Reims Champagne-Ardenne, 51100, France.
authors: F
authors: F
authors: Edwards-Lévy
authors: Inserm UMR1073, Nutrition, Gut and Brain Laboratory, Rouen 76183, France; Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, 76000, France. Electronic address: Serguei.Fetissov@univ-rouen.fr.
authors: S O
authors: SO
authors: Fetissov
mesh_terms: D000418:Albumins; D000464:Alginates; D000818:Animals; D019440:Anti-Obesity Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D060766:Drinking Water / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000295:instrumentation* / Q000379:methods; D004435:Eating / Q000187:drug effects; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D007031:Hypothalamus / Q000187:drug effects* / Q000503:physiopathology; D007276:Injections, Intraventricular; D008297:Male; D009479:Neuropeptides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D000521:alpha-MSH / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000418:Albumins; D000464:Alginates; D019440:Anti-Obesity Agents; D060766:Drinking Water; D006603:Hexuronic Acids; D009479:Neuropeptides; D000521:alpha-MSH; D020723:Glucuronic Acid
keywords: brain delivery; eating disorders; feeding behavior; microparticles; neuropeptides; obesity