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

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

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 AA

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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