Coenzyme Q10 Alleviates Renal Injury through Modulating Lipid Metabolism in ApoE-deficient Mice Fed a High-fat Diet Based on Lipidomic Analysis

Dyslipidemia is a significant risk factor for chronic kidney disease (CKD). Coenzyme Q10 (CoQ10), commonly recognized as a dietary supplement, exhibits a wide range of biological activities. This study aimed to investigate the efficacy of CoQ10 in mitigating renal damage in apolipoprotein E-deficient (ApoE^-/-) mice subjected to a high-fat diet (HFD). The findings revealed that a 12-week supplementation of CoQ10 (1800 mg/kg diet) significantly decreased HFD-induced elevations in levels of renal function parameters, including serum uric acid (SUA; from (54.84 ± 6.35) to (37.96 ± 5.25) μmol/L; <em>P </em>&lt; 0.001), creatinine (SCr; from (22.72 ± 2.69) to (14.02 ± 2.72) μmol/L; <em>P </em>&lt; 0.001), and blood urea nitrogen (BUN; from (5.79 ± 0.65) to (3.70 ± 1.01) mmol/L; <em>P </em>&lt; 0.001). Moreover, CoQ10 supplementation significantly ameliorated HFD-induced pathological alterations, lipid accumulation (<em>P </em>&lt; 0.01), oxidative stress (<em>P </em>&lt; 0.01), inflammation (<em>P </em>&lt; 0.05), and fibrosis (<em>P </em>&lt; 0.01) in the kidneys. Furthermore, untargeted lipidomics analysis of the kidneys demonstrated that CoQ10 effectively promoted the recovery of differential lipid species, primarily including glycerophospholipids (GP), glycerolipids (GL), and sphingolipids (SP) in HFD-fed mice (<em>P </em>&lt; 0.05). Additionally, targeted lipidomic analysis of GP suggested that a HFD led to an increase in renal concentrations of various lipid metabolites, primarily within the osphatidylcholines (PC) and 1-(1Z-alkenyl),2-acylglycerophosphoethanolamines (PE_P) classes. These alterations were favorably restored by CoQ10 supplementation (<em>P </em>&lt; 0.05). Furthermore, Western blot analysis demonstrated that CoQ10 significantly downregulated renal PI3K/Akt (<em>P </em>&lt; 0.01) and TLR4/MyD88/NFκB (<em>P </em>&lt; 0.05) signaling pathways in HFD-fed mice. Consequently, this study suggests that CoQ10 exerts a potent regulatory effect on lipid metabolism disorders induced by a HFD, thereby contributing to the mitigation of renal injury under hyperlipidemic conditions.