Obesity is a global health threat, and the induction of white adipose tissue (WAT) browning presents a promising therapeutic method for it. Recent publications revealed the essential role of protein arginine methyltransferase 4 (PRMT4) in lipid metabolism and adipogenesis, but its involvement in WAT browning has not been investigated. Our initial studies found that the expression of PRMT4 in adipocytes was upregulated in cold-induced WAT browning but downregulated in obesity. Besides, PRMT4 overexpression in inguinal adipose tissue accelerated WAT browning and thermogenesis to protect against high-fat dietāinduced obesity and metabolic disruptions. Mechanistically, our work demonstrated that PRMT4 methylated peroxisome proliferator-activated receptor-Ī³ (PPARĪ³) on Arg240 to enhance its interaction with the coactivator PR domain-containing protein 16 (PRDM16), leading to the increased expression of thermogenic genes. Taken together, our results uncover the essential role of the PRMT4/PPARĪ³/PRDM16 axis in the pathogenesis of WAT browning.
Article Highlights
- Protein arginine methyltransferase 4 (PRMT4) expression was upregulated during cold exposure and negatively correlated with body mass of mice and humans.
- PRMT4 overexpression in inguinal white adipose tissue of mice improved high-fat dietāinduced obesity and associated metabolic impairment due to enhanced heat production.
- PRMT4 methylated peroxisome proliferator-activated receptor-Ī³ on Arg240 and facilitated the binding of the coactivator PR domain-containing protein 16 to initiate adipose tissue browning and thermogenesis.
- PRMT4-dependent methylation of peroxisome proliferator-activated receptor-Ī³ on Arg240 is important in the process of inguinal white adipose tissue browning.
