ADAR1 inhibits adipogenesis and obesity by interacting with Dicer to promote the maturation of miR-155-5P

Abstract

Adipogenesis is closely related to various metabolic diseases, such as obesity, type 2 diabetes, cardiovascular diseases and cancer. This cellular process is highly dependent on the expression and sequential activation of a diverse group of transcription factors. Here, we report that ADAR1 (also known as ADAR) could inhibit adipogenesis through binding with Dicer (also known as DICER1), resulting in enhanced production of miR-155-5p, which downregulates the adipogenic early transcription factor C/EBPβ. Consequently, the expression levels of late-stage adipogenic transcription factors (C/ EBPα and PPARγ) are reduced and adipogenesis is inhibited. More importantly, in vivo studies reveal that overexpression of ADAR1 suppresses white adipose tissue expansion in high fat diet-induced obese mice, leading to improved metabolic phenotypes, such as insulin sensitivity and glucose tolerance.