Liver-adipose tissue crosstalk in alcohol-associated liver disease: The role of mTOR

作     者：Yssa Rodriguez Jack Dunfield Tyson Roderique Hong-Min Ni Yssa Rodriguez;Jack Dunfield;Tyson Roderique;Hong-Min Ni

作者机构：Department of PharmacologyToxicology and TherapeuticsUniversity of Kansas Medical CenterKansas CityKSUSA 

出 版 物：《Liver Research》 (肝脏研究（英文）)

年 卷 期：2022年第6卷第4期

页      面：227-237页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：The research was supported in part by the USA NIDDK DK129234,NIAAA AA026904 NIGMS P20GM144269 P30GM118247(to H.-M.Ni) 

主　　题：Alcohol-associated liver disease(ALD) Liver injury Mechanistic target of rapamycin(mTOR) Adipose atrophy Adipokine Liver-adipose tissue crosstalk 

摘      要：Background:Alcohol-associated liver disease(ALD)is a major chronic liver disease around the world without successful *** alcoholic hepatitis is one of the most severe forms of ALD with high mortality,which is often associated with binge *** drinking dysregulates lipid metabolism,increases adipose tissue lipolysis,and induces liver steatosis and adipose tissue *** ev-idence implicates that crosstalk of liver and adipose tissue in the pathogenesis of *** target of rapamycin(mTOR)is a phosphatidylinositol 3-kinase(PI3K)-like serine/threonine protein kinase that regulates lipid metabolism,cell proliferation and ***,the role of mTOR in regulating adipose-liver crosstalk in binge drinking-induced organ damage remains ***:We generated liver-specific and adipocyte-specific regulatory-associated protein of mTOR(Rptor)knockout(Rptor LKO and Rptor AKO)as well as Mtor knockout(Mtor LKO and Mtor AKO)mice,by crossing Rptor flox and Mtor flox mice with albumin Cre or adiponectin Cre mice,*** addition,we generated liver and adipocyte double deletion of Rptor or Mtor(Mtor LAKO and Rptor LAKO)*** knockout mice with their matched wild-type littermates(Rptor WT and Mtor WT)were subjected to acute gavage of 7 g/kg ***:Mice with adipocyte deletion of Rptor or Mtor developed hepatomegaly and adipose tissue *** gavage increased liver injury,hepatic steatosis and inflammation in mouse livers as demonstrated by elevated serum alanine aminotransferase activities,increased hepatic levels of tri-glyceride and increased hepatic numbers of CD68 positive macrophages in mouse livers after alcohol *** injury was further exacerbated by deletion of adipocyte Rptor or *** adipokine array analysis revealed that increased levels of pro-inflammatory cytokines IL-6 and TNF a as well as chemokine MCP-1 following acute alcohol gavage in wild-type mice,which were further incr