Protein arginine methyltransferase (PRMT) 1 regulates glucose metabolism in the liver and catabolic pathways in the skeletal muscle, suggesting its role as an important regulator of metabolic pathway. However, the role of PRMT1 in the fat tissues has not been explored to date. Here, we delineate the function of PRMT1 in adipocytes by using adipocyte-specific PRMT1 knockout (PRMT1 FKO) mice. PRMT1 expression is abundant in white adipose tissues (WAT) but not in brown adipose tissues (BAT), and is induced upon high fat diet, prompting us to explore the phenotype of PRMT1 FKO mice in diet-induced obesity (DIO) conditions. We found that the depletion of adipose PRMT1 reduced the weight of WAT, with a reciprocal increase in the liver weight without changes in overall body weight. We found that activation of autophagy and mitochondrial biogenesis led to the increased energy expenditure and the decreased fat cell size of WAT, while lipid accumulation was eminent in BAT and the liver. Furthermore, we observed an impaired glucose homeostasis upon PRMT1 depletion, as evidenced by the higher plasma glucose levels and impaired insulin tolerance in PRMT1 FKO mice compared with the control. These data collectively suggest that PRMT1 protects WAT from excessive degradation of stored triglycerides to control whole body energy homeostasis in DIO conditions.