Omega-3 Fatty Acids Attenuate LPS-Induced Acute Kidney Injury via Activation of AMPK/SIRT1/PGC-1α/NRF2/FOXO3 Signaling and Suppression of NF-κB-Mediated Inflammation

Ahmet B. Halil A. Oznur K. Yusuf T.M. Sinan K. Ilter I. Gulsum B.T. Ozlem O.
February 2026 Multidisciplinary Digital Publishing Institute (MDPI)

Nutrients
2026 #18 Issue 4

Background: Sepsis-induced acute kidney injury (AKI) involves oxidative stress and inflammation. Omega-3 (OMG-3) fatty acids possess antioxidant properties, but their impact on the mitochondrial AMPK/SIRT1/PGC-1α/NRF2/FOXO3 axis in AKI remains unclear. Methods: Thirty-two male Wistar rats were divided into Control, LPS (5 mg/kg), LPS + OMG-3 (500 mg/kg/day), and OMG-3 groups. Renal tissues were analyzed for histopathology, immunohistochemistry (TNF-α, Caspase-3, HSP70), and gene expression (AMPK, SIRT1, PPGC-1α NRF2, FOXO3). Results: LPS caused severe tubular injury, increased TNF-α, Caspase-3, and HSP70 expression, while significantly downregulating the AMPK/SIRT1/PGPGC-1αRF2/FOXO3 signaling pathway. OMG-3 treatment alleviated histopathological damage, suppressed inflammatory and apoptotic markers, and restored the expression of mitochondrial and antioxidant genes. Conclusions: OMG-3 fatty acids protect against LPS-induced AKI by upregulating the gene expression of components in the AMPK/SIRT1/PGCPGC-1αF2/FOXO3 axis and suppressing NF-κB-driven inflammation. This dual regulation highlights OMG-3 as a potential therapeutic agent for sepsis-related renal injury.

apoptosis , Heme oxygenase 1 , HSP70 , inflammation , Interleukin 6 , omega-3 fatty acids , oxidative stress

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Department of Anesthesiology and Reanimation, Faculty of Medicine, Suleyman Demirel University, Türkiye, Isparta, 32260, Kazakhstan
Department of Pharmacology, Faculty of Medicine, Suleyman Demirel University, Türkiye, Isparta, 32260, Kazakhstan
Department of Pharmacology, Institute of Health Sciences, Suleyman Demirel University, Isparta, 32260, Turkey
Department of Medical Genetic, Faculty of Medicine, Suleyman Demirel University, Türkiye, Isparta, 32260, Kazakhstan
Department of Biochemistry, Faculty of Medicine, Suleyman Demirel University, Türkiye, Isparta, 32260, Kazakhstan
Burn Unit, Isparta City Hospital General Surgery Clinic, Isparta, 32200, Turkey
Department of Pathology, Faculty of Veterinary Medicine, Burdur Mehmet Akif Ersoy University, Burdur, 15030, Turkey

Department of Anesthesiology and Reanimation
Department of Pharmacology
Department of Pharmacology
Department of Medical Genetic
Department of Biochemistry
Burn Unit
Department of Pathology

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