Peripheral Cannabinoid-1 Receptor Inverse Agonism Reduces Obesity by Reversing Leptin Resistance

• Published in: Cell metabolism Vol. 16; no. 2; pp. 167 - 179
• Main Authors: Tam, Joseph, Cinar, Resat, Liu, Jie, Godlewski, Grzegorz, Wesley, Daniel, Jourdan, Tony, Szanda, Gergő, Mukhopadhyay, Bani, Chedester, Lee, Liow, Jeih-San, Innis, Robert B., Cheng, Kejun, Rice, Kenner C., Deschamps, Jeffrey R., Chorvat, Robert J., McElroy, John F., Kunos, George
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.08.2012
• Subjects: adipocytes; Adipocytes - metabolism; agonistic behavior; agonists; Animals; Anti-Obesity Agents - chemistry; Anti-Obesity Agents - pharmacology; Anti-Obesity Agents - therapeutic use; appetite; Body Weight - drug effects; Drug Inverse Agonism; Drug Resistance - drug effects; energy expenditure; fatty liver; Fatty Liver - drug therapy; Fatty Liver - etiology; Insulin Resistance; kidneys; leptin; Leptin - metabolism; Mice; Molecular Structure; obesity; Obesity - complications; Obesity - drug therapy; Obesity - metabolism; Pyrazoles - chemistry; Pyrazoles - pharmacology; Pyrazoles - therapeutic use; Receptor, Cannabinoid, CB1 - agonists; Regression Analysis; risk; secretion; Sulfonamides - chemistry; Sulfonamides - pharmacology; Sulfonamides - therapeutic use; weight loss

Obesity-related leptin resistance manifests in loss of leptin’s ability to reduce appetite and increase energy expenditure. Obesity is also associated with increased activity of the endocannabinoid system, and CB1 receptor (CB1R) inverse agonists reduce body weight and the associated metabolic compl...