Abstract
Dysregulation in lipid metabolism is the leading cause of chronic kidney disease (CKD) and also the important risk factors for high morbidity and mortality. Although lipid abnormalities were identified in CKD, integral metabolic pathways for specific individual lipid species remain to be clarified. We conducted ultra-high-performance liquid chromatography-high-definition mass spectrometry-based lipidomics and identified plasma lipid species and therapeutic effects of Rheum officinale in CKD rats. Adenine-induced CKD rats were administered Rheum officinale. Urine, blood and kidney tissues were collected for analyses. We showed that exogenous adenine consumption led to declining kidney function in rats. Compared with control rats, a panel of differential plasma lipid species in CKD rats was identified in both positive and negative ion modes. Among the 50 lipid species, phosphatidylcholine (PC), lysophosphatidylcholine (LysoPC) and lysophosphatidic acid (LysoPA) accounted for the largest number of identified metabolites. We revealed that six PCs had integral metabolic pathways, in which PC was hydrolysed into LysoPC, and then converted to LysoPA, which was associated with increased cytosolic phospholipase A2 protein expression in CKD rats. The lower levels of six PCs and their corresponding metabolites could discriminate CKD rats from control rats. Receiver operating characteristic curves showed that each individual lipid species had high values of area under curve, sensitivity and specificity. Administration of Rheum officinale significantly improved impaired kidney function and aberrant PC metabolism in CKD rats. Taken together, this study demonstrates that CKD leads to PC metabolism disorders and that the dysregulation of PC metabolism is involved in CKD pathology.
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Acknowledgements
This study was supported by the National Natural Science Foundation of China (Nos. 81703691 and 82074002), Shaanxi Key Science and Technology Plan Project (No. 2019ZDLSF04-04-02) and ShaanXi Science and Technology Innovation Team (No. 2019TD-016).
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YYZ designed the study. YNW, ZHZ, HJL, and ZYG performed the experiments. YYZ performed the statistical analysis. YYZ prepared the manuscript. LZ and YMZ revised the manuscript. All authors read and approved the final manuscript.
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Wang, Yn., Zhang, Zh., Liu, Hj. et al. Integrative phosphatidylcholine metabolism through phospholipase A2 in rats with chronic kidney disease. Acta Pharmacol Sin 44, 393–405 (2023). https://doi.org/10.1038/s41401-022-00947-x
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DOI: https://doi.org/10.1038/s41401-022-00947-x
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