摘要：SummaryFibrosis is the pathophysiological hallmark of progressive chronic kidney disease (CKD). The kidney is a highly metabolically active organ, and it has been suggested that disruption in its metabolism leads to renal fibrosis. We developed a longitudinal mouse model of acute kidney injury leading to CKD and anin vitromodel of epithelial to mesenchymal transition to study changes in metabolism, inflammation, and fibrosis. Using transcriptomics, metabolic modeling, and serum metabolomics, we observed sustained fatty acid metabolic dysfunction in the mouse model from early to late stages of CKD. Increased fatty acid biosynthesis and downregulation of catabolic pathways for triglycerides and diacylglycerides were associated with a marked increase in these lipids in the serum. We therefore suggest that the kidney may be the source of the abnormal lipid profile seen in patients with CKD, which may provide insights into the association between CKD and cardiovascular disease.Graphical AbstractDisplay OmittedHighlights•Following AKI, markers of fibrosis and inflammation go up simultaneously•AKI is associated with reduced fatty acid oxidation and oxidative phosphorylation•Changes in metabolism persist as chronic kidney disease develops•Changes in metabolism are associated with increased serum levels of triglyceridesHuman Metabolism; Systems Biology; Omics
