Peripheral CB1 cannabinoid receptor blockade improves cardiometabolic risk in mouse models of obesity.

ABSTRACT: Obesity and its metabolic consequences are a major public health concern worldwide. Obesity is associated with overactivity of the endocannabinoid system, which is involved in the regulation of appetite, lipogenesis, and insulin resistance. Cannabinoid-1 receptor (CB1R) antagonists reduce body weight and improve cardiometabolic abnormalities in experimental and human obesity, but their therapeutic potential is limited by neuropsychiatric side effects. Here we have demonstrated that a CB1R neutral antagonist largely restricted to the periphery does not affect behavioral responses mediated by CB1R in the brains of mice with genetic or diet-induced obesity, but it does cause weight-independent improvements in glucose homeostasis, fatty liver, and plasma lipid profile. These effects were due t

SUBMITTER: Tam J 

PROVIDER: S-EPMC2912197 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature