Resistance to diet-induced obesity in mu-opioid receptor-deficient mice: evidence for a "thrifty gene".
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.
Tabarin
Antoine
A
Laboratoire Homéostasie-Allostasie-Pathologie, EA 3666, University of Bordeaux 2, 146 Rue Leo Saignat, 33076 Bordeaux, France. antoine.tabarin@chu-bordeaux.fr
Diz-Chaves
Y
Y
Chaves
Yolanda Diz
YD
Carmona
Maria del Carmen
Mdel C
Catargi
Bogdan
B
Zorrilla
Eric P
EP
Roberts
Amanda J
AJ
Coscina
Donald V
DV
Rousset
Sophie
S
Redonnet
Anabelle
A
Parker
Graham C
GC
Inoue
Koki
K
Ricquier
Daniel
D
Pénicaud
Luc
L
Kieffer
Brigitte L
BL
Koob
Georges F
GF
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*
D017450:Receptors, Opioid, mu