The RNA-binding protein HuR is a negative regulator in adipogenesis

Human antigen R (HuR) is a universally expressed RNA-binding protein that regulates RNA metabolism, yet its metabolic functions are unclear. This study identifies HuR as a major repressor of adipogenesis. In primary adipocyte cultures, HuR knockdown enhances, and HuR overexpression inhibits, adipogenesis in vitro. Adipose tissue–specific knockout of Hur markedly augments adipogenic gene programs and increases fat mass in mice, accompanied by systemic glucose intolerance and insulin resistance. HuR loss also yields depot-specific phenotypes: repression of myogenesis programs in brown fat, increased inflammation programs in epididymal white fat, and induction of browning programs in inguinal white fat. Mechanistically, HuR recognizes and modulates the stability of hundreds of adipocyte transcripts, including Insig1, a negative regulator of adipogenesis, thereby inhibiting adipocyte differentiation. These findings establish Hur as an important posttranscriptional regulator of adipogenesis and provide insight into RNA processing in adipocyte development.

Diana Teh Chee Siang, Yen Ching Lim, Aung Maung Maung Kyaw, Khaing Nwe Win, Sook Yoong Chia, Ufuk Degirmenci, Xiang Hu, Bryan C. Tan, Arcinas Camille Esther Walet, Lei Sun, Dan Xu