Estrogen-related receptor gamma regulates hepatic triglyceride metabolism through phospholipase A2 G12B

摘要

Hypersecretion of hepatic very LDL (VLDL)-associated triglyceride (TG) is the hallmark of hypertriglyceridemia. The estrogen-related receptor gamma (ERR gamma), an orphan nuclear receptor, plays crucial roles in the regulation of metabolic homeostasis, including TG formation in the liver. It remains unclear whether ERR gamma regulates hepatic VLDL-TG secretion. We demonstrated that knockdown of ERR gamma impairs hepatic VLDL-TG secretion in mice, whereas overexpression of ERR gamma favors the secretion, indicating a novel role of ERR gamma in hepatic TG metabolism. We found that ERR gamma transcriptionally regulates the expression of PLA2G12B by binding to the promoter region of the Pla2g12b gene. In Pla2g12b-null mice, ERR gamma fails to regulate hepatic VLDL-TG secretion. There is an apparent accumulation of large lipid droplets in the liver of Pla2g12b-null mice. These data suggest that ERR gamma is a novel regulator of hepatic VLDL-TG secretion, which is mediated through the action on PLA2G12B.-Chen, L., Wu, M., Zhang, S., Tan, W., Guan, M., Feng, L., Chen, C., Tao, J., Chen, L., Qu, L. Estrogen-related receptor gamma regulates hepatic triglyceride metabolism through phospholipase A2 G12B.