title: Resistance to diet-induced obesity in mu-opioid receptor-deficient mice: evidence for a "thrifty gene".
abstract: Using pharmacological tools, a role for opioid receptors in the regulation of food intake has been documented. However, the involvement of specific receptor subtypes remains questionable, and little information is available regarding a role for opioid receptors in energy metabolism. Using adult male mice lacking the mu-opioid receptor (MOR) gene (MOR-/-), we show that the MOR is not essential for the maintenance of normal levels of ad libitum food intake but does modulate the efficiency of energy storage during high-fat diets through the regulation of energy partitioning. When fed a regular diet, MOR-/- mice displayed only subtle alterations in energy homeostasis, suggesting a relative overuse of fat as a fuel source in the fed state. When fed a high-fat diet, MOR-/- mice were resistant to obesity and impaired glucose tolerance, despite having similar energy intake to wild-type mice. This resistance to obesity was associated with a strong induction of the expression of key mitochondrial enzymes involved in fatty acid oxidation within skeletal muscle. This metabolic role of the MOR, which is consistent with the properties of a "thrifty gene," suggests that the MOR pathway is a potential target for pharmacological intervention in the treatment of obesity associated with the intake of fatty diets.
authors.affiliation: Laboratoire Homéostasie-Allostasie-Pathologie, EA 3666, University of Bordeaux 2, 146 Rue Leo Saignat, 33076 Bordeaux, France. antoine.tabarin@chu-bordeaux.fr
authors.forename: Antoine
authors.initials: A
authors.lastname: Tabarin
authors.forename: Y
authors.initials: Y
authors.lastname: Diz-Chaves
authors.forename: Yolanda Diz
authors.initials: YD
authors.lastname: Chaves
authors.forename: Maria del Carmen
authors.initials: Mdel C
authors.lastname: Carmona
authors.forename: Bogdan
authors.initials: B
authors.lastname: Catargi
authors.forename: Eric P
authors.initials: EP
authors.lastname: Zorrilla
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Roberts
authors.forename: Donald V
authors.initials: DV
authors.lastname: Coscina
authors.forename: Sophie
authors.initials: S
authors.lastname: Rousset
authors.forename: Anabelle
authors.initials: A
authors.lastname: Redonnet
authors.forename: Graham C
authors.initials: GC
authors.lastname: Parker
authors.forename: Koki
authors.initials: K
authors.lastname: Inoue
authors.forename: Daniel
authors.initials: D
authors.lastname: Ricquier
authors.forename: Luc
authors.initials: L
authors.lastname: Pénicaud
authors.forename: Brigitte L
authors.initials: BL
authors.lastname: Kieffer
authors.forename: Georges F
authors.initials: GF
authors.lastname: Koob
mesh_terms: D000818:Animals; D004038:Diet, Reducing; D004435:Eating; D004734:Energy Metabolism; D005215:Fasting; D006706:Homeostasis; D007030:Hypothalamo-Hypophyseal System; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics*; D010913:Pituitary-Adrenal System; D017450:Receptors, Opioid, mu / Q000172:deficiency* / Q000235:genetics*
chemical_list: D017450:Receptors, Opioid, mu