MiR‐21‐3p Inhibits Adipose Browning by Targeting FGFR1 and Aggravates Atrial Fibrosis in Diabetes
Jianan Pan, Hao Lin, Jianying Yu, Huili Zhang, Jun-feng Zhang, Chang-qian Wang, Jun Gu
Abstract
A relationship between excess epicardial adipose tissue (EAT) and the risk of atrial fibrillation (AF) has been reported. Browning of EAT may be a novel approach for the prevention or treatment of AF by attenuating atrial fibrosis. Previous studies have identified microRNA‐21 (miR‐21) as a regulatory factor in atrial fibrosis. The present study examined the role of different subtypes of miR‐21 in adipose browning and atrial fibrosis under hyperglycemic conditions. Wild type and miR‐21 knockout C57BL/6 mice were used to establish a diabetic model via intraperitoneal injection of streptozotocin. A coculture model of atrial fibroblasts and adipocytes was also established. We identified miR‐21‐3p as a key regulator that controls adipocyte browning and participates in atrial fibrosis under hyperglycemic conditions. Moreover, fibroblast growth factor receptor (FGFR) 1, a direct target of miR‐21‐3p, decreased in this setting and controlled adipose browning. Gain and loss‐of‐function experiments identified a regulatory pathway in adipocytes involving miR‐21a‐3p, FGFR1, FGF21, and PPAR γ that regulated adipocyte browning and participated in hyperglycemia‐induced atrial fibrosis. Modulation of this signaling pathway may provide a therapeutic option for the prevention and treatment of atrial fibrosis or AF in DM.