Melatonin alleviates PM_2.5 -induced glucose metabolism disorder and lipidome alteration by regulating endoplasmic...

Area of Science:

• Environmental Health
• Hepatology
• Molecular Biology

Background:

• Fine particulate matter (PM2.5) exposure is linked to increased liver metabolic disease.
• Melatonin is known to prevent liver glucolipid metabolism disorders.
• The protective effect of melatonin against PM2.5-induced liver damage is not fully understood.

Purpose of the Study:

• To evaluate melatonin's mitigating effect on PM2.5-accelerated hepatic glucose metabolism imbalance.
• To investigate the molecular mechanisms underlying PM2.5-induced liver metabolic abnormalities.
• To explore the therapeutic potential of melatonin in air pollution-related liver disorders.

Main Methods:

• In vivo and in vitro experiments using ApoE-/- mice and L02 cells.
• Schiff periodic acid Schiff staining, targeted lipidomics, gene microarray, and quantitative polymerase chain reaction.
• Luciferase reporter assays to verify gene targeting relationships.
• Analysis of endoplasmic reticulum stress markers and key proteins involved in glucose metabolism.

Main Results:

• PM2.5 exposure decreased hepatic glycogen and increased glucose, which melatonin alleviated.
• PM2.5 activated miR-200a-3p and inhibited DNAJB9, a relationship confirmed by luciferase assays.
• DNAJB9 regulates endoplasmic reticulum stress via Ca2+ homeostasis, impacting GSK3B, FOXO1, and PCK2.
• Melatonin inhibited miR-200a-3p, alleviating PM2.5-induced glucose metabolism disorder and ER stress.
• Knockout of miR-200a-3p confirmed its role in PM2.5-induced liver damage and melatonin's therapeutic effect.

Conclusions:

• Melatonin alleviates PM2.5-induced liver metabolic dysregulation.
• The protective mechanism involves regulating endoplasmic reticulum stress via the miR-200a-3p/DNAJB9 signaling pathway.
• Melatonin offers a potential targeted therapy for liver metabolic disorders associated with air pollution.