CIDEC as a novel player in abdominal aortic aneurysm formation

Abdominal aortic aneurysm (AAA) is a degenerative lesion characterized by structural disruption of the abdominal aortic wall and progressive dilatation into a pulsatile mass. AAA is strongly associated with obesity, partly due to abnormal dilatation of perivascular adipose tissue (PVAT) in the abdomen, however, direct evidence is still lacking.

Cell death-inducing DNA fragmentation factor-like effector C (CIDEC), also known as fat-specific protein 27 (FSP27) in rodents, is a lipid droplet (LD)-associated protein that plays an important role in lipid storage. It has been reported that CIDEC/FSP27 promotes the growth of LDs by mediating the exchange and transfer of lipids at the contact sites of LDs. A recent study showed that FSP27-deficient mice were resistant to obesity induced by high-fat diet (HFD) or leptin deficiency (ob/ob). Considering the physiological and pathological roles, it is intriguing to investigate whether or not CIDEC/FSP27 is involved in PVAT dysfunction and the AAA pathogenesis.

Recently, a study published in Life Metabolism titled "CIDEC/FSP27 exacerbates obesity-related abdominal aortic aneurysm by promoting perivascular adipose tissue inflammation" reports that CIDEC/FSP27 enhances PVAT inflammation and macrophage infiltration, thereby exacerbating the formation of AAA induced by HFD and angiotensin Ⅱ (Ang Ⅱ).

The investigators first found that FSP27 deficiency attenuated HFD-induced pathological dilation and inflammation of the PVAT in mice. They further found that CIDEC/FSP27 deficiency prevented both HFD and Ang Ⅱ-induced AAA formation. Transcriptome analysis revealed significant differences between Fsp27^fl/fl and adipocyte tissue-specific Fsp27 knockout mice (Fsp27^AKO). In particular, matrix metalloproteinase 12 (MMP12) levels and macrophage infiltration were significantly reduced in the aorta of Fsp27^AKO mice. Based on these results, the investigators hypothesized that the decreased macrophage accumulation in the aorta may be due to a reduction in chemokine secretion by perivascular adipocytes. FSP27 was shown to promote adipocyte expression and secretion of the chemokine CCL2 (C–C motif chemokine ligand 2), which increases macrophage migration through the CCL2/C-C motif chemokine receptor 2 (CCR2) axis (Figure 1).

In conclusion, this study demonstrates that global or adipose tissue-specific knockout of CIDEC/FSP27 significantly reduces AAA incidence after HFD treatment and Ang Ⅱ infusion, providing novel insights into the inflammatory mechanisms of PVAT during AAA progression and highlighting the potential of CIDEC/FSP27 as a therapeutic target for obesity-related AAA.