First Author | Tang Y | Year | 2023 |
Journal | Cell Rep | Volume | 42 |
Issue | 1 | Pages | 111948 |
PubMed ID | 36640325 | Mgi Jnum | J:332900 |
Mgi Id | MGI:7430628 | Doi | 10.1016/j.celrep.2022.111948 |
Citation | Tang Y, et al. (2023) Exosomal miR-27b-3p secreted by visceral adipocytes contributes to endothelial inflammation and atherogenesis. Cell Rep 42(1):111948 |
abstractText | 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-kappaB pathway by downregulating PPARalpha. Mechanistically, miR-27b-3p binds directly to the CDS region of PPARalpha 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 PPARalpha protects against atherosclerosis. Thus, obesity-induced exosomal miR-27b-3p promotes endothelial inflammation and facilitates atherogenesis by PPARalpha suppression. We reveal an exosomal pathway by which obesity aggravates atherosclerosis and proposed therapeutic strategies for atherosclerosis in people with obesity. |