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

## TL;DR

Brown remodeling of fat tissue protects against aortic aneurysms by secreting a protective protein called FSTL1.

## Contribution

The study identifies FSTL1 as a novel protective batokine that inhibits vascular cell death in AAA.

## Key findings

- AAA patients have reduced adipose tissue browning levels.
- FSTL1 inhibits vascular smooth muscle cell apoptosis via DIP2A/AKT signaling.
- FSTL1 supplementation reduces aortic dilation and AAA progression in mice.

## 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.

Brown remodeling of white adipose tissue inhibited abdominal aortic aneurysm (AAA) progression via a vessel-protective adipokine Follistatin-like 1 (FSTL1), suggesting a novel therapeutic strategy for AAA intervention.

Browning level is decreased in AAA patients and browning induction in mice attenuates AAA development.Browning adipocytes secrete FSTL1 and inhibit VSMC apoptosis via receptor Dip2A-mediated Akt activation.Adipocyte-specific FSTL1 deficiency abrogates the protective effect of browning induction.Supplementation of recombinant FSTL1 attenuates AAA development.

Browning level is decreased in AAA patients and browning induction in mice attenuates AAA development.

Browning adipocytes secrete FSTL1 and inhibit VSMC apoptosis via receptor Dip2A-mediated Akt activation.

Adipocyte-specific FSTL1 deficiency abrogates the protective effect of browning induction.

Supplementation of recombinant FSTL1 attenuates AAA development.

CETN3 loss-of-function mutations were identified in a primary microcephaly patient. Mechanistic studies revealed that CETN3 knockout results in impaired centrosome assembly, disrupted neurogenesis, and defective neural precursor cell (NPC) proliferation.