DHA-enriched phosphatidylserine ameliorates high-fat diet-induced kidney injury in mice possibly by regulating TLR4/NF-κB and AMPK pathways

Abstract

The present study sought to investigate the amelioration effects of enzymatically synthesized docosahexaenoic acid-enriched phosphatidylserine (DHA-PS) on the high-fat diet (HFD)-induced kidney injury in mice. After 6 weeks of DHA-PS intervention, the mice's body weight in the 20 and 40 mg/kg DHA-PS groups decreased by 7.09% and 9.71%, respectively, compared to the HFD group. Especially, compared to the HFD group, 40 mg/kg DHA-PS treatment effectively reduced the levels of serum urea nitrogen by 68.48%, creatinine by 38.98%, kidney lipid accumulation (total cholesterol, triglycerides, and nonesterified fatty acids levels by 26.19%, 51.00%, and 26.11%), kidney or serum proinflammatory cytokines and enhanced the levels of kidney or serum oxidative stress parameters, except for malondialdehyde (MDA). Moreover, 40 mg/kg DHA-PS treatment decreased the expression levels of toll-like receptor 4 (TLR4) by 18.63%, IKKα by 31.81%, and p-p65 by 40.73% in the nuclear factor kappa-B pathway, thereby upregulating the expression levels of p-AMPKα by 64.93%, HSL by 99.60%, ATGL by 344.50%, PPARα by 162.02%, CPT1 by 167.95%, p-ACC1 by 144.92%, and p-SREBP1 by 1172.95%, and downregulating the expression levels of SREBP1 by 38.80%, ACC1 by 18.10%, and FAS by 82.28% in the AMPK pathway. Furthermore, our results also suggested that improving serum or kidney parameters and regulating intestinal microbial could affect each other after DHA-PS treatment. These results elucidated that DHA-PS could be a potential dietary supplement to alleviate HFD-induced kidney injury. PRACTICAL APPLICATION: Our results elucidated that DHA-PS could be a potential dietary supplement to alleviate HFD-induced kidney injury.

Keywords: AMPK pathway; DHA-enriched phosphatidylserine; NF-κB pathway; high-fat diet; kidney injury.