Poster Presentation ANZOS-ASLM-ICCR 2019

Peripheral cannabinoid 1 receptor antagonism improves insulin sensitivity by suppressing adipose tissue inflammation in mouse models of obesity (#151)

Ji Hye Han 1 , Wook Kim 1
  1. Ajou University, Youngtong-Gu, SUWON, South Korea

Adipose tissue inflammation caused by obesity, associated with the development of insulin resistance, in which NLRP3 inflammasome acts as a pivotal mediator. Cannabinoid 1 receptor (CB1R) antagonists have been shown to improve insulin resistance and associated metabolic abnormalities, but treatment development has been halted due to side effects of neuropsychiatry. While increasing evidence suggests CB1R's role in inflammatory signals, their direct impact on adipose tissue inflammation has yet to be evaluated. Here we report that CB1R antagonist AJ-compound, which is limited in peripheral, has beneficial metabolic effects comparable to its brain permeable parenting compound rimonabant, suppress macrophages infiltration into white adipose tissue, activation of NLRP3 inflammasome, and the production of inflammatory cytokine in diet-induced obese mice. Furthermore, we have identified the downstream signal path in which CB1R regulates inflammatory gene expression. These results suggest that the peripheral CB1R blockade enhances obesity-causing insulin resistance by inhibiting adipose tissue inflammation through NLRP3 inflammasome.