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

Abstract

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.

Keywords:

• Cecum ligation perforation
• organ injury
• inflammation

Author contributions

Peng Liu and Ming Li contributed to data collection, statistical analysis, data interpretation and manuscript preparation. Chengzhi Yi contributed to data collection and manuscript preparation. Wei Wu, Anjie Liu, Honglin Hu, and Qin Liu contributed to data collection and data interpretation.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Additional information

Funding

The present study was supported by the Youth Project of the Wuhan Municipal Health and Family Planning Commission [grant no. WX18Y06].