Peripheral cannabinoid-1 receptor blockade restores hypothalamic leptin signaling.

ABSTRACT: OBJECTIVE:In visceral obesity, an overactive endocannabinoid/CB1 receptor (CB1R) system promotes increased caloric intake and decreases energy expenditure, which are mitigated by global or peripheral CB1R blockade. In mice with diet-induced obesity (DIO), inhibition of food intake by the peripherally restricted CB1R antagonist JD5037 could be attributed to endogenous leptin due to the rapid reversal of hyperleptinemia that maintains leptin resistance, but the signaling pathway engaged by leptin has remained to be determined. METHODS:We analyzed the hypothalamic circuitry targeted by leptin following chronic treatment of DIO mice with JD5037. RESULTS:Leptin treatment or an increase in endogenous leptin following fasting/refeeding induced STAT3 phosphorylation in neurons in the arcuate nucle

SUBMITTER: Tam J 

PROVIDER: S-EPMC5641628 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature