title: Role of hypothalamic melanocortin system in adaptation of food intake to food protein increase in mice.
abstract: The hypothalamic melanocortin system--the melanocortin receptor of type 4 (MC4R) and its ligands: α-melanin-stimulating hormone (α-MSH, agonist, inducing hypophagia), and agouti-related protein (AgRP, antagonist, inducing hyperphagia)--is considered to play a central role in the control of food intake. We tested its implication in the mediation of the hunger-curbing effects of protein-enriched diets (PED) in mice. Whereas there was a 20% decrease in food intake in mice fed on the PED, compared to mice fed on an isocaloric starch-enriched diet, there was a paradoxical decrease in expression of the hypothalamic proopiomelanocortin gene, precursor of α-MSH, and increase in expression of the gene encoding AgRP. The hypophagia effect of PED took place in mice with invalidation of either MC4R or POMC, and was even strengthened in mice with ablation of the AgRP-expressing neurons. These data strongly suggest that the hypothalamic melanocortin system does not mediate the hunger-curbing effects induced by changes in the macronutrient composition of food. Rather, the role of this system might be to defend the body against the variations in food intake generated by the nutritional environment.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U855, Lyon, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Pillot
authors.forename: Céline
authors.initials: C
authors.lastname: Duraffourd
authors.forename: Martine
authors.initials: M
authors.lastname: Bégeot
authors.forename: Aurélie
authors.initials: A
authors.lastname: Joly
authors.forename: Serge
authors.initials: S
authors.lastname: Luquet
authors.forename: Isabelle
authors.initials: I
authors.lastname: Houberdon
authors.forename: Danielle
authors.initials: D
authors.lastname: Naville
authors.forename: Michèle
authors.initials: M
authors.lastname: Vigier
authors.forename: Amandine
authors.initials: A
authors.lastname: Gautier-Stein
authors.forename: Christophe
authors.initials: C
authors.lastname: Magnan
authors.forename: Gilles
authors.initials: G
authors.lastname: Mithieux
mesh_terms: D054369:Agouti-Related Protein / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004044:Dietary Proteins / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects* / Q000235:genetics; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000521:alpha-MSH / Q000235:genetics / Q000378:metabolism
chemical_list: D054369:Agouti-Related Protein; D004044:Dietary Proteins; D044105:Receptor, Melanocortin, Type 4; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin