Resistance to diet-induced obesity in mu-opioid receptor-deficient mice: evidence for a "thrifty gene"

• Published in: Diabetes (New York, N.Y.) Vol. 54; no. 12; pp. 3510 - 3516
• Main Authors: Tabarin, Antoine, Diz-Chaves, Yolanda, Chaves, Yolanda Diz, del Carmen Carmona, Maria, Catargi, Bogdan, Zorrilla, Eric P., Roberts, Amanda J., Coscina, Donald V., Rousset, Sophie, Redonnet, Anabelle, Parker, Graham C., Inoue, Koki, Ricquier, Daniel, Pénicaud, Luc, Kieffer, Brigitte, Koob, Georges F.
• Format: Journal Article
• Language: English
• Published: American Diabetes Association 2005
• Subjects: Biochemistry, Molecular Biology; Life Sciences
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.54.12.3510

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.