Brown remodeling of white adipose tissue protects against abdominal aortic aneurysm via batokine FSTL1.

Abstract

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease without effective medical therapies. Emerging evidence have suggested a crosstalk between adipose tissue and vascular cells. Besides, brown adipose tissue is considered beneficial for cardiovascular health. Nevertheless, whether brown remodeling of white adipose tissue would protect against AAA remains unclear. Here, we showed that patients with AAA had a decreased browning level of adipose tissue, and induction of adipose tissue browning significantly reduced AAA incidence and attenuated AAA development in mice. Using LC-MS/MS and proteomic analysis, we further identified Follistatin-like 1 (FSTL1) as a novel vessel-protective adipokine secreted by browning adipocytes. Mechanistically, FSTL1 inhibited VSMC apoptosis through DIP2A/AKT signaling. Furthermore, we demonstrated that adipocyte-specific deficiency of FSTL1 abrogated the protective effect of browning induction. Moreover, supplementation of FSTL1 either systemically or patched into hydrogel placing around the abdominal aorta markedly limited aortic dilation and AAA progression. Our data suggest a protective role of adipose tissue browning and batokine FSTL1 in the development of AAA, which may represent a novel intervention strategy for AAA.