Resolvin D1 reduces ER stress-induced apoptosis and triglyceride accumulation through JNK pathway in HepG2 cells

Area of Science:

• Cellular Biology
• Metabolic Disorders
• Pharmacology

Background:

• Endoplasmic reticulum (ER) stress is implicated in metabolic disorders like obesity, type 2 diabetes mellitus, and non-alcoholic fatty liver disease (NAFLD).
• Resolvins, derived from ω-3 fatty acids, possess anti-inflammatory and insulin-sensitizing properties, suggesting a therapeutic role in metabolic dysfunctions.

Purpose of the Study:

• To investigate the protective effects of resolvin D1 (RvD1) against ER stress-induced cellular damage and steatosis in liver cells.
• To elucidate the molecular mechanisms underlying RvD1's action, particularly its involvement with the JNK pathway.

Main Methods:

• HepG2 cells were pretreated with RvD1 and subjected to tunicamycin to induce ER stress.
• Assessed apoptosis, caspase 3 activity, triglyceride accumulation, SREBP-1 expression, ER stress markers, and JNK pathway activation.
• Utilized anisomycin, a JNK activator, to confirm the role of JNK in RvD1's protective effects.

Main Results:

• RvD1 pretreatment attenuated ER stress-induced apoptosis and decreased caspase 3 activity in HepG2 cells.
• RvD1 significantly reduced tunicamycin-induced triglyceride accumulation and SREBP-1 expression.
• RvD1 inhibited tunicamycin-induced c-Jun N-terminal kinase (JNK) expression, while anisomycin-induced JNK activation effects were reversed by RvD1.

Conclusions:

• RvD1 confers cellular protection against ER stress-induced hepatic steatosis and apoptosis, acting downstream of ER stress.
• The protective mechanism involves the modulation of the JNK-mediated pathway.
• RvD1 represents a potential therapeutic strategy for non-alcoholic fatty liver disease (NAFLD).