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

Life metabolism Pub Date : 2024-09-18 eCollection Date: 2025-02-01 DOI:10.1093/lifemeta/loae035
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
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Abstract

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 angiotensin Ⅱ (Ang Ⅱ)-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.

CIDEC/FSP27通过促进血管周围脂肪组织炎症加重肥胖相关性腹主动脉瘤。
腹主动脉瘤(AAA)与肥胖密切相关,部分原因是腹部血管周围脂肪组织(PVAT)的异常扩张。细胞死亡诱导DNA片段化因子样效应物C (CIDEC),也被称为脂肪特异性蛋白27 (FSP27),在啮齿类动物中特异性表达,介导脂滴融合和脂肪组织扩张。CIDEC/FSP27是否以及如何在AAA病理中起作用尚不清楚。在这里,我们表明FSP27加剧肥胖和血管紧张素Ⅱ(AngⅡ)诱导的AAA进展。小鼠FSP27缺乏抑制高脂饮食诱导的PVAT扩张和炎症。整体和脂肪组织特异性FSP27消融均可显著降低肥胖相关的AAA发生率。脂肪细胞中FSP27的缺乏会破坏主动脉组织中基质金属蛋白酶-12 (MMP12)的表达。与MMP12部分共定位的浸润性巨噬细胞在fsp27缺失的主动脉中显著减少。在机制上,3T3-L1脂肪细胞中Fsp27的下调通过c-Jun n -末端激酶(JNK)依赖途径抑制C-C基模趋化因子配体2 (CCL2)的表达和分泌,从而导致巨噬细胞迁移诱导减少,而Cidec的过表达则恢复了这一作用。总体而言,我们的研究表明,脂肪组织中的CIDEC/FSP27通过增强PVAT炎症和巨噬细胞浸润,至少在一定程度上促进了肥胖相关AAA的形成,从而阐明了其作为肥胖相关AAA的关键调节因子的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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