Adipocyte RNA-binding protein CELF1 promotes beiging of white fat through stabilizing Dio2 mRNA.

Abstract

RNA-binding proteins (RBPs) regulate diverse post-transcriptional processes and play roles in adipocyte development; however, their role in white fat beiging remains unclear. Here we identify CUG-BP Elav-like family member 1 (CELF1) as a key RBP promoting beiging of inguinal white adipose tissue in response to cold. Adipocyte-specific Celf1 deficiency impairs cold-induced thermogenic gene expression and reduces energy expenditure. Mechanistically, CELF1 binds to the 3'UTR of Dio2 mRNA and enhances its stability, promoting local triiodothyronine (T3) production. Notably, CELF1 expression is significantly reduced in subcutaneous fat of individuals with obesity and negatively correlates with BMI. CELF1 enhances isoproterenol-induced beige adipocyte activation and mitochondrial respiration in vitro, and Celf1 overexpression ameliorates diet-induced obesity and metabolic dysfunction. Hence, our study identifies CELF1 as a physiological regulator of metabolic stress in activating thermogenesis and promoting energy expenditure at the post-transcriptional level, highlighting its potential as a therapeutic target for obesity and metabolic diseases.