Human antigen R (HuR) is an essential regulator of RNA metabolism, but its function in metabolism remains unclear. This study identifies HuR as a major repressor during adipogenesis. Knockdown and overexpression of HuR in primary adipocyte culture enhances and inhibits adipogenesis *in vitro*, respectively. Fat-specific knockout of *Hur* significantly enhances adipogenic gene program in adipose tissues, accompanied by a systemic glucose intolerance and insulin resistance. HuR knockout also results in depot-specific phenotypes: it can repress myogenesis program in brown fat, enhance inflammation program in epididymal white fat and induce browning program in inguinal white fat. Mechanistically, HuR may inhibit adipogenesis by recognizing and modulating the stability of hundreds of adipocyte transcripts including Insig1, a negative regulator during adipogenesis. Taken together, our work establishes *Hur* as an important posttranscriptional regulator of adipogenesis and provides insights into how RNA processing contributes to 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