title: Intestinal inflammation influences α-MSH reactive autoantibodies: relevance to food intake and body weight.
abstract: Autoantibodies reacting with alpha-melanocyte-stimulating hormone (α-MSH), an anorexigenic neuropeptide, are involved in regulation of feeding. In this work we studied if intestinal inflammation (mucositis) may influence α-MSH autoantibodies production relevant to food intake and body weight. Mucositis and anorexia were produced in Sprague-Dawley rats by methotrexate (MTX, 2.5mg/kg/day, for three days, subcutaneously). Plasma levels of total IgG and of α-MSH autoantibodies were measured during and after MTX-induced mucositis and were compared with pair-fed and ad libitum-fed controls. Effects of intraperitoneal injections of rabbit anti-α-MSH IgG (3 or 10 μg/day/rat) on MTX-induced anorexia and on plasma α-MSH peptide concentration were separately studied. Here we show that in MTX rats, intestinal mucositis and anorexia were accompanied by decreased plasma levels of both total IgG and of α-MSH autoantibodies while refeeding was characterized by their elevated levels. In spite of similar food intake in MTX and pair-fed rats, recovery of body weight was delayed by at least 1 week in the MTX group. During refeeding and body weight deficit in MTX rats, α-MSH IgG autoantibody levels correlated negatively with food to water intake ratios. Injections of anti-α-MSH IgG induced a dose-dependent attenuation of food intake and body weight regain in MTX-treated rats accompanied by increased concentrations of α-MSH peptide which correlated positively with plasma levels of α-MSH autoantibodies. These data show that intestinal inflammation, independently from food restriction, affects general humoral immune response which may influence food intake and body weight control via modulation of α-MSH plasma concentration by α-MSH reactive autoantibodies.
authors.affiliation: Digestive System & Nutrition Laboratory (ADEN EA4311), Institute of Medical Research and Innovation, Rouen University, IFR23, Rouen 76183, France.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Coquerel
authors.forename: Maria Hamze
authors.initials: MH
authors.lastname: Sinno
authors.forename: Nabile
authors.initials: N
authors.lastname: Boukhettala
authors.forename: Moïse
authors.initials: M
authors.lastname: Coëffier
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Terashi
authors.forename: Christine
authors.initials: C
authors.lastname: Bole-Feysot
authors.forename: Denis
authors.initials: D
authors.lastname: Breuillé
authors.forename: Pierre
authors.initials: P
authors.lastname: Déchelotte
authors.forename: Sergueï O
authors.initials: SO
authors.lastname: Fetissov
mesh_terms: D000818:Animals; D000855:Anorexia / Q000097:blood / Q000139:chemically induced / Q000150:complications / Q000276:immunology* / Q000503:physiopathology*; D001323:Autoantibodies / Q000097:blood*; D001835:Body Weight / Q000276:immunology* / Q000502:physiology; D004195:Disease Models, Animal; D004326:Drinking / Q000276:immunology / Q000502:physiology; D004435:Eating / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000494:pharmacology; D008297:Male; D008727:Methotrexate; D052016:Mucositis / Q000097:blood / Q000139:chemically induced / Q000150:complications / Q000276:immunology* / Q000503:physiopathology*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D000521:alpha-MSH / Q000097:blood / Q000276:immunology* / Q000502:physiology
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D000521:alpha-MSH; D008727:Methotrexate