Acetylation of PPARγin macrophages promotes visceral fat degeneration in obesity

作     者：Nicole Aaron Tarik Zahr Ying He Lexiang Yu Brent Mayfield Utpal BPajvani Li Qiang 

作者机构：Naomi Berrie Diabetes CenterColumbia UniversityNew YorkNYUSA Department of PharmacologyColumbia UniversityNew YorkNYUSA Department of Pathology and Cell BiologyColumbia UniversityNew YorkNYUSA Department of Genetics and DevelopmentColumbia UniversityNew YorkNYUSA Department of MedicineColumbia UniversityNew YorkNYUSA 

出 版 物：《Life Metabolism》 (生命（代谢（英文）)

年 卷 期：2022年第1卷第3期

页      面：258-269页

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：This work was supported by the National Institutes of Health F31DK124926(N.A.) T32DK007328(N.A.) R01DK112943(L.Q.) R01DK128848(L.Q.) R01DK131169(U.B.P.and L.Q.) and P01 HL087123(L.Q.) 

主　　题：PPARγacetylation adipose tissue remodeling macrophage inflammation fibrosis 

摘      要：Obesity is characterized by chronic,low-grade inflammation,which is driven by macrophage infiltration of adipose ***γ is well established to have an anti-inflammatory function in macrophages,but the mechanism that regulates its function in these cells remains to be fully ***γundergoes post-translational modifications(PTMs),including acetylation,to mediate ligand responses,including on metabolic ***,we report that PPARγacetylation in macrophages promotes their infiltration into adipose tissue,exacerbating metabolic *** generated a mouse line that expresses a macrophage-specific,constitutive acetylation-mimetic form of PPARγ(K293Q^(flox/flox):LysM-cre,mK293Q)to dissect the role of PPARγacetylation in *** highfat diet feeding to stimulate macrophage infiltration into adipose tissue,we assessed the overall metabolic profile and tissue-specific phenotype of the mutant mice,including responses to the PPARγagonist ***-specific PPARγK293Q expression promotes proinflammatory macrophage infiltration and fibrosis in epididymal white adipose tissue,but not in subcutaneous or brown adipose tissue,leading to decreased energy expenditure,insulin sensitivity,glucose tolerance,and adipose tissue ***,mK293Q mice are resistant to Rosiglitazone-induced improvements in adipose tissue *** study reveals that acetylation is a new layer of PPARγregulation in macrophage activation,and highlights the importance and potential therapeutic implications of such PTMs in regulating metabolism.