83 adrenergic receptor activation alleviated PM2.5-induced hepatic lipid deposition in mice

Increasing energy expenditure through activation of hepatocytes is a potential approach to treat fine particulate matter (PM2.5) induced metabolic-associated fatty liver disease (MAFLD). Beta-3 adrenergic receptor (83-AR) agonists could stimulate brown adipose tissue (BAT) energy expenditure, but it has never been investigated in MAFLD. The objective of this study is to explore the therapeutic effects of administering CL-316,243, a selective agonist of 83-AR, on hepatic lipid metabolism disturbances induced by PM2.5. Firstly, C57BL/6 N mice were intraperitoneally injected with CL-316,243 for one week. CL-316,243 significantly upregulated expression of 83 -AR in the liver, accompanied with reduced serum triglyceride (TG) and free fatty acids (FFA). Next, mice were subjected to PM2.5 exposure for 4 weeks, and CL-316,243 was daily intraperitoneally injected in the fourth week of PM2.5 exposure. Exposure to PM2.5 led to a significant increase in hepatic TG and monounsaturated fatty acids (MUFAs), accompanied with elevated activity of SCD1, increased levels of TG synthesis enzymes and inhibited COX4 activity. Furthermore, the administration of CL-316,243 alleviated PM2.5-induced hepatic lipid deposition by enhancing SCD1 activity, TG lipolysis, fatty acid oxidation and TG synthesis via 03-AR/PKA/CREB/PPAR signaling pathway. Therefore, 03-AR activation may serve as a potential therapeutic approach for PM2.5 exposure-induced MAFLD.