Brown adipose tissue-derived Nrg4 alleviates endothelial inflammation and atherosclerosis in male mice

• Type of Material: Article
• Authors: Lingfeng Shi, General Hospital of Central Theater Command; Yixiang Li, Emory University School of Medicine; Xiaoli Xu, General Hospital of Central Theater Command; Yangyang Cheng, General Hospital of Central Theater Command; Biying Meng, General Hospital of Central Theater Command; Jinling Xu, Southern Medical University; Lin Xiang, General Hospital of Central Theater Command; Jiajia Zhang, General Hospital of Central Theater Command; Kaiyue He, Southern Medical University; Jiayue Tong, Southern Medical University; Junxia Zhang, General Hospital of Central Theater Command; Lingwei Xiang, Brigham and Women's Hospital; Guangda Xiang, General Hospital of Central Theater Command
• Language: English
• Date: 2022-11-01
• Publisher: Springer Nature Limited
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2022, corrected publication 2022
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s42255-022-00671-0
• Title of Journal or Parent Work: Nature Metabolism
• Volume: 4
• Issue: 11
• Start Page: 1573
• End Page: 1590
• Keywords: Atherosclerosis; Inflammation; Male; Endothelial Cells; Endothelium; Adipose Tissue, Brown; Animals; Neuregulins; Mice
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

Brown adipose tissue (BAT) activity contributes to cardiovascular health by its energy-dissipating capacity but how BAT modulates vascular function and atherosclerosis through endocrine mechanisms remains poorly understood. Here we show that BAT-derived neuregulin-4 (Nrg4) ameliorates atherosclerosis in mice. BAT-specific Nrg4 deficiency accelerates vascular inflammation and adhesion responses, endothelial dysfunction and apoptosis and atherosclerosis in male mice. BAT-specific Nrg4 restoration alleviates vascular inflammation and adhesion responses, attenuates leukocyte homing and reduces endothelial injury and atherosclerosis in male mice. In endothelial cells, Nrg4 decreases apoptosis, inflammation and adhesion responses induced by oxidized low-density lipoprotein. Mechanistically, protein kinase B (Akt)–nuclear factor-κB signaling is involved in the beneficial effects of Nrg4 on the endothelium. Taken together, the results reveal Nrg4 as a potential cross-talk factor between BAT and arteries that may serve as a target for atherosclerosis.