Resistin Regulates Inflammation and Insulin Resistance in Humans via the Endocannabinoid System  

作　　者：Han-Mo Yang Joonoh Kim Baek-Kyung Kim Hyun Ju Seo Ju-Young Kim Joo-Eun Lee Jaewon Lee Jihye You Sooryeonhwa Jin Yoo-Wook Kwon Hyun-Duk Jang Hyo-Soo Kim 

机构地区：[1]Department of Internal Medicine,Seoul National University Hospital,Seoul,Korea [2]National Research Laboratory for Stem Cell Niche,Seoul National University Hospital,Seoul,Korea [3]Innovative Research Institute for Cell Therapy,Seoul National University Hospital,Seoul,Korea [4]Molecular Medicine and Biopharmaceutical Sciences,Seoul National University,Seoul,03080,Korea

出　　处：《Research》2024年第4期596-607,共12页研究(英文)

基　　金：supported by grants of the Korea Health Technology R&D Project“Korea Research-Driven Hospital(HI14C1277)”through the KHIDI;funded by the Korea Government(MHW)and by Korea Drug Development Fund funded by Ministry of Science and ICT,Ministry of Trade,Industry,and Energy,and Ministry of Health and Welfare(HN21C0524);National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(no.RS-2023-00228390).

摘　　要：Resistin plays an important role in the pathophysiology of obesity-mediated insulin resistance in mice.However,the biology of resistin in humans is quite different from that in rodents.Therefore,the association between resistin and insulin resistance remains unclear in humans.Here,we tested whether and how the endocannabinoid system(ECS)control circulating peripheral blood mononuclear cells(PBMCs)that produce resistin and infiltrate into the adipose tissue,heart,skeletal muscle,and liver,resulting in inflammation and insulin resistance.Using human PBMCs,we investigate whether the ECS is connected to human resistin.To test whether the ECS regulates inflammation and insulin resistance in vivo,we used 2 animal models such as“humanized”nonobese diabetic/Shi-severe combined immunodeficient interleukin-2Rγ(null)(NOG)mice and“humanized”resistin mouse models,which mimic human body.In human atheromatous plaques,cannabinoid 1 receptor(CB1R)-positive macrophage was colocalized with the resistin expression.In addition,resistin was exclusively expressed in the sorted CB1R-positive cells from human PBMCs.In CB1R-positive cells,endocannabinoid ligands induced resistin expression via the p38–Sp1 pathway.In both mouse models,a high-fat diet increased the accumulation of endocannabinoid ligands in adipose tissue,which recruited the CB1R-positive cells that secrete resistin,leading to adipose tissue inflammation and insulin resistance.This phenomenon was suppressed by CB1R blockade or in resistin knockout mice.Interestingly,this process was accompanied by mitochondrial change that was induced by resistin treatment.These results provide important insights into the ECS–resistin axis,leading to the development of metabolic diseases.Therefore,the regulation of resistin via the CB1R could be a potential therapeutic strategy for cardiometabolic diseases.

关 键 词：INFLAMMATION expression. RESISTIN 

分 类 号：R58[医药卫生—内分泌]