Melatonin Alleviates PM2.5-Induced Hepatic Steatosis and Metabolic-Associated Fatty Liver Disease in ApoE-/- Mice.

Abstract

Background:

Exposure to fine particulate matter (PM2.5) is associated with the risk of developing metabolic-associated fatty liver disease (MAFLD). Melatonin is the main secreted product of the pineal gland and has been reported to prevent hepatic lipid metabolism disorders. However, it remains uncertain whether melatonin could protect against PM2.5-induced MAFLD.

Methods and Results:

The purpose of our study was to investigate the mitigating effects of melatonin on hepatic fatty degeneration accelerated by PM2.5 in vivo and in vitro. Histopathological analysis and ultrastructural images showed that PM2.5 induced hepatic steatosis and lipid vacuolation in ApoE-/- mice, which could be effectively alleviated by melatonin administration. Increased ROS production and decreased expression of antioxidant enzymes were detected in the PM2.5-treated group, whereas melatonin showed recovery effects after PM2.5-induced oxidative damage in both the liver and L02 cells. Further investigation revealed that PM2.5 induced oxidative stress to activate PTP1B, which in turn had a positive feedback regulation effect on ROS release. When a PTP1B inhibitor or melatonin was administered, SP1/SREBP-1 signalling was effectively suppressed, while Nrf2/Keap1 signalling was activated in the PM2.5-treated groups.

Conclusion:

Our study is the first to show that melatonin alleviates the disturbance of PM2.5-triggered hepatic steatosis and liver damage by regulating the ROS-mediated PTP1B and Nrf2 signalling pathways in ApoE-/- mice. These results suggest that melatonin administration might be a prospective therapy for the prevention and treatment of MAFLD associated with air pollution.

• Authors: Zhou Du, Shuang Liang, Yang Li, Jingyi Zhang, Yang Yu, Qing Xu, Zhiwei Sun, Junchao Duan
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2022 Pg. 8688643 ( 2022) ISSN: 1942-0994 [Electronic] United States
• PMID: 35720187 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Zhou Du et al.

Chemical References

• Apolipoproteins E
• Kelch-Like ECH-Associated Protein 1
• NF-E2-Related Factor 2
• Particulate Matter
• Reactive Oxygen Species
• Melatonin

Topics

• Animals
• Apolipoproteins E (genetics, metabolism)
• Fatty Liver (metabolism)
• Kelch-Like ECH-Associated Protein 1 (metabolism)
• Liver (metabolism)
• Melatonin (metabolism, pharmacology, therapeutic use)
• Mice
• NF-E2-Related Factor 2 (metabolism)
• Oxidative Stress
• Particulate Matter (metabolism, toxicity)
• Reactive Oxygen Species (metabolism)