Protective effect of omega-3 polyunsaturated fatty acids on sepsis via the AMPK/mTOR pathway

Context: Sepsis is a systemic inflammatory response caused by Infection, with high morbidity and mortality. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) have reported biological activities.

Objective: This study explored the signaling pathways through which ω-3 PUFAs protect against sepsis-induced multiorgan failure.

Materials and methods: Septic Sprague-Dawley (SD) rat model was established by the cecum ligation perforation (CLP) method. Rats were divided into control, sham, model, parenteral ω-3 PUFAs (0.5 g/kg) treatment, ω-3 PUFAs (0.5 g/kg) + AMPK Inhibitor Compound C (30 mg/kg) treatment, and ω-3 PUFAs (0.5 g/kg) + mTOR Activator MHY1485 (10 mg/kg) treatment groups. The serum inflammatory cytokines were measured using ELISA. Organ damage-related markers cTnI, CK, CK-MB, Cr, BUN, ALT, and AST were measured using an automated chemical analyzer. The AMPK/mTOR pathway in liver, kidney, and myocardial tissues was detected using western blot and qRT-PCR methods.

Results: CLP treatment enhanced the secretion of pro-inflammatory cytokines and multi-organ related markers, along with increased p-AMPK/AMPK ratio (from 0.47 to 0.87) and decreased p-mTOR/mTOR ratio (from 0.33 to 0.12) in rats. The inflammation response and multi-organ injury induced by CLP treatment could be partially counteracted by 0.5 g/kg parenteral ω-3 PUFA treatment. The activated AMPK/mTOR pathway in CLP-induced rats was further promoted. Finally, Compound C and MHY1485 could reverse the effects of parenteral ω-3 PUFA treatment on sepsis rats.

Discussion and conclusion: ω-3 PUFAs ameliorated sepsis development by activating the AMPK/mTOR pathway, serving as a potent therapeutic agent for sepsis. Further in vivo studies may validate potential clinical use.

Cecum ligation perforation; inflammation; organ injury.