Metabolic and inflammatory functions of cannabinoid receptor type 1 are differentially modulated by adiponectin  

作　　者：Qiong Wei Jong Han Lee Chia-Shan Wu Qun S Zang Shaodong Guo Hui-Chen Lu Yuxiang Sun 

机构地区：[1]Department of Endocrinology,Zhongda Hospital,School of Medicine,Southeast University,Nanjing 210009,Jiangsu Province,China [2]Department of Pediatrics,USDA/ARS Children’s Nutrition Research Center,Baylor College of Medicine,Houston,TX 77030,United States [3]Department of Marine Bioindustry,Hanseo University,Seosan 31962,South Korea [4]Department of Nutrition,Texas A and M University,College Station,TX 7743,United States [5]Department of Surgery,Stritch School of Medicine,Loyola University Chicago Health Science Campus,Maywood,IL 60153,United States [6]Department of Psychological and Brain Sciences,Linda and Jack Gill Center of for Biomolecular Science,Bloomington,IN 47405,United States

出　　处：《World Journal of Diabetes》2021年第10期1750-1764,共15页世界糖尿病杂志（英文版）（电子版）

基　　金：Supported by the NIH,No.DK118334 and No.AG064869;and the BrightFocus,No.A2019630S(to Sun Y).

摘　　要：BACKGROUND Antagonists of cannabinoid type 1 receptor(CB1)have been shown to promote body weight loss and improve insulin sensitivity.Cannabinoids decrease adiponectin,and CB1 blocker increase adiponectin.However,the mediators of CB1 actions are not well defined.AIM To investigate whether the beneficial effects of CB1 inhibition are,at least in part,mediated by adiponectin.METHODS We compared metabolic and inflammatory phenotypes of wild-type(WT)mice,CB1-null(CB1^(-/-))and CB1/adiponectin double-knockout(DKO)mice.We assessed the insulin sensitivity using insulin tolerance test and glucose tolerance test,and inflammation using flow cytometry analysis of macrophages.RESULTS CB1^(-/-)mice exhibited significantly reduced body weight and fat mass when compared to WT mice.While no significance was found in total daily food intake and locomotor activity,CB1^(-/-)mice showed increased energy expenditure,enhanced thermogenesis in brown adipose tissue(BAT),and improved insulin sensitivity compared to WT mice.DKO showed no difference in body weight,adiposity,nor insulin sensitivity;only showed a modestly elevated thermogenesis in BAT compared to CB1^(-/-)mice.The metabolic phenotype of DKO is largely similar to CB1^(-/-)mice,suggesting that adiponectin is not a key mediator of the metabolic effects of CB1.Interestingly,CB1^(-/-)mice showed reduced pro-inflammatory macrophage polarization in both peritoneal macrophages and adipose tissue macrophages compared to WT mice;in contrast,DKO mice exhibited increased pro-inflammatory macrophage polarization in these macrophages compared to CB1^(-/-)mice,suggesting that adiponectin is an important mediator of the inflammatory effect of CB1.CONCLUSION Our findings reveal that CB1 functions through both adiponectin-dependent and adiponectin-independent mechanisms:CB1 regulates energy metabolism in an adiponectin-independent manner,and inflammation in an adiponectin-dependent manner.The differential effects of adiponectin on CB1-mediated metabolic and inflammatory functions should be ta

关 键 词：Cannabinoid type 1 receptor ADIPONECTIN THERMOGENESIS MACROPHAGES Inflammation Insulin resistance 

分 类 号：R965[医药卫生—药理学]