Exosomal miR-27b-3p secreted by visceral adipocytes contributes to endothelial inflammation and atherogenesis
Yan Tang,
Li-Jie Yang,
Hao Liu,
Yan-Jue Song,
Qi-Qi Yang,
Yang Liu,
Shu-Wen Qian,
Qi-Qun Tang
Affiliations
Yan Tang
Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology of School of Basic Medical Sciences and Department of Endocrinology and Metabolism of Zhongshan Hospital, Fudan University, Shanghai 200032, China
Li-Jie Yang
Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology of School of Basic Medical Sciences and Department of Endocrinology and Metabolism of Zhongshan Hospital, Fudan University, Shanghai 200032, China
Hao Liu
Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiaotong University of Medicine College, Shanghai 200032, China
Yan-Jue Song
Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology of School of Basic Medical Sciences and Department of Endocrinology and Metabolism of Zhongshan Hospital, Fudan University, Shanghai 200032, China
Qi-Qi Yang
Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology of School of Basic Medical Sciences and Department of Endocrinology and Metabolism of Zhongshan Hospital, Fudan University, Shanghai 200032, China
Yang Liu
Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology of School of Basic Medical Sciences and Department of Endocrinology and Metabolism of Zhongshan Hospital, Fudan University, Shanghai 200032, China
Shu-Wen Qian
Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology of School of Basic Medical Sciences and Department of Endocrinology and Metabolism of Zhongshan Hospital, Fudan University, Shanghai 200032, China
Qi-Qun Tang
Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology of School of Basic Medical Sciences and Department of Endocrinology and Metabolism of Zhongshan Hospital, Fudan University, Shanghai 200032, China; Corresponding author
Summary: Obesity, particularly increased visceral fat, positively correlates with various metabolic challenges, including atherosclerosis, but the mechanism is not fully understood. The aim of this study is to determine the role of visceral-fat-derived exosomes (Exo) in endothelial cells and atherosclerosis. We show that obesity changes the miRNA profile of visceral adipose exosomes in mice. Importantly, exosomal miR-27b-3p efficiently enters into the vascular endothelial cells and activates the NF-κB pathway by downregulating PPARα. Mechanistically, miR-27b-3p binds directly to the CDS region of PPARα mRNA, thereby promoting mRNA degradation and suppressing translation. In ApoE-deficient mice, administration of miR-27b-3p mimic increases inflammation and atherogenesis, while overexpression of PPARα protects against atherosclerosis. Thus, obesity-induced exosomal miR-27b-3p promotes endothelial inflammation and facilitates atherogenesis by PPARα suppression. We reveal an exosomal pathway by which obesity aggravates atherosclerosis and proposed therapeutic strategies for atherosclerosis in people with obesity.
