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Peripheral cannabinoid 1 receptor blockade mitigates adipose tissue inflammation via NLRP3 inflammasome in mouse models of obesity.

 Ji H. Han  ;  Hanho Shin  ;  Jun G. Rho  ;  Jung‐Eun Kim  ;  Dong H. Son  ;  Juhwan Yoon  ;  Yong J. Lee  ;  Jung‐Hyuck Park  ;  Byung J. Song  ;  Chang-Sik Choi  ;  Seul G. Yoon  ;  il Y. Kim  ;  Eun K. Lee  ;  Je K. Seong DVM  ;  Ki W. Kim  ;  Wook Kim 
 DIABETES OBESITY & METABOLISM, Vol.20(9) : 2179-2189, 2018 
Journal Title
Issue Date
adipose tissue inflammation ; insulin resistance ; obesity ; peripheral cannabinoid 1 receptor
AIM: To analyze the metabolic parameters and adipose tissue inflammation via NLRP3 inflammasome following chronic treatment of mouse models of obesity with AJ5018 as the peripherally restricted cannabinoid 1 receptor (CB1R) antagonist. MATERIALS AND METHODS: The selectivity for CB1R over CB2R, brain/plasma concentration ratio, and centrally mediated neurobehavioural effects of AJ5018, were assessed. The long-term effects of AJ5018 and rimonabant on the metabolic parameters and adipose tissue inflammation were analyzed in diet-induced obese (DIO) mice and diabetic db/db mice. RESULTS: AJ5018 had a higher degree of selectivity for CB1R over CB2R and markedly reduced brain penetrance, as reflected by the lower brain/plasma concentration ratio and the attenuated centrally mediated neurobehavioural effects, compared with its brain-penetrant parent compound rimonabant. In DIO and db/db mice, AJ5018 exhibited comparable effects to rimonabant in improving metabolic abnormalities and suppressing macrophage infiltration into white adipose tissue, activation of the NLRP3 inflammasome, and production of proinflammatory cytokines. CONCLUSIONS: These results suggest that peripheral CB1R blockade improves obesity-induced insulin resistance by suppressing adipose tissue inflammation via the NLRP3 inflammasome.
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Ki Woo(김기우) ORCID logo https://orcid.org/0000-0002-7790-1515
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