CIDEC/FSP27 exacerbates obesity-related abdominal aortic aneurysm by promoting perivascular adipose tissue inflammation  

作　　者：Qing Zhu Da Luo Yining Li Liyang Yu Zixuan Zhang Feng Ouyang Liangkui Li Manxi Lu Changyong Hu Yinuo Dong Chengxin Ma Yan Liang Tong-Jin Zhao Feng-Jung Chen Peng Li Tian-Shu Yang 

机构地区：[1]Shanghai Key Laboratory of Metabolic Remodeling and Health,Institute of Metabolism and Integrative Biology,Institutes of Biomedical Sciences,Fudan University,Shanghai 200438,China [2]Shanghai Qi Zhi Institute,Shanghai 200030,China [3]State Key Laboratory of Membrane Biology and Tsinghua-Peking Center for Life Sciences,Beijing Advanced Innovation Center for Structural Biology,School of Life Sciences,Tsinghua University,Beijing 100086,China [4]School of Life Sciences,Tianjian Laboratory of Advanced Biomedical Sciences,Zhengzhou University,Zhengzhou,Henan 450001,China [5]Shanghai Key Laboratory of Lung Inflammation and Injury,Department of Pulmonary Medicine,Zhongshan Hospital,Fudan University,Shanghai 200032,China

出　　处：《Life Metabolism》2025年第1期35-49,65,共16页生命代谢(英文)

基　　金：supported by the National Natural Science Foundation of China(32271334,32100945,and 81871228);the National Key R&D Program of China(2018YFA0506900 and 2018YFA0800301);Shanghai Basic Research Field Project“Science and Technology Innovation Action Plan”(21JC1400400);the Lingang Laboratory(LG-QS-202204-06);the High-Level Medicine Foundation of Shanghai Government(to P.L.);Shanghai Municipal Science and Technology Major Project(2017SHZDZX01).

摘　　要：Abdominal aortic aneurysm(AAA)is strongly correlated with obesity,partially due to the abnormal expansion of abdominal perivascular adipose tissue(PVAT).Cell death-inducing DNA fragmentation factor-like effector C(CIDEC),also known as fat-specific protein 27(FSP27)in rodents,is specifically expressed in adipose tissue where it mediates lipid droplet fusion and adipose tissue expansion.Whether and how CIDEC/FSP27 plays a role in AAA pathology remains elusive.Here,we show that FSP27 exacerbates obesity and angiotensinⅡ(AngⅡ)-induced AAA progression.FSP27 deficiency in mice inhibited high-fat diet-induced PVAT expansion and inflammation.Both global and adipose tissue-specific FSP27 ablation significantly decreased obesity-related AAA incidence.Deficiency of FSP27 in adipocytes abrogated matrix metalloproteinase-12(MMP12)expression in aortic tissues.Infiltrated macrophages,which partially colocalize with MMP12,were significantly decreased in the FSP27-deficient aorta.Mechanistically,knockdown of Fsp27 in 3T3-L1 adipocytes inhibited C-C motif chemokine ligand 2(CCL2)expression and secretion through a c-Jun N-terminal kinase(JNK)-dependent pathway,thereby leading to reduced induction of macrophage migration,while Cidec overexpression rescued this effect.Overall,our study demonstrates that CIDEC/FSP27 in adipose tissue contributes to obesity-related AAA formation,at least in part,by enhancing PVAT inflammation and macrophage infiltration,thus shedding light on its significance as a key regulator in the context of obesity-related AAA.

关 键 词：AAA INFLAMMATION PVAT Cidec CCL2 

分 类 号：R589.2[医药卫生—内分泌] R543.16[医药卫生—内科学]