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Citrate is a central metabolite in cellular energy regulation and is frequently elevated in advanced kidney disease, yet its impact on renal lipid metabolism has not been investigated. This study tested whether increased circulating citrate promotes lipid accumulation in the kidney by activating acetyl\u2010CoA carboxylase independently of adenosine monophosphate\u2010activated protein kinase.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male Munich Wistar Fr\u00f6mter rats, a genetic model of chronic kidney disease, were studied together with HEK293 cells exposed to citrate. Protein expression, phosphorylation, and polymerization were assessed using western blotting, q\u2010RT\u2010PCR, and native gel electrophoresis. Renal lipid composition was characterized by untargeted high\u2010performance liquid chromatography coupled with quadrupole time\u2010of\u2010flight mass spectrometry, and citrate levels were semi\u2010quantified using capillary electrophoresis\u2013time\u2010of\u2010flight mass spectrometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MWF rats exhibited elevated plasma citrate, reduced vitamin D and bone mineral density, and increased renal fibrosis and mitochondrial dysfunction. Moreover, MWF showed higher expression of ATP\u2010citrate lyase and fatty acid synthase, together with reduced phosphorylation of acetyl\u2010CoA carboxylase and AMP\u2010activated protein kinase, increased renal lipid deposition, and elevated fatty acid content. In HEK293, citrate treatment reproduced these effects, inducing acetyl\u2010CoA carboxylase polymerization, lipid droplet formation, impaired mitochondrial activity, and increased superoxide production.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study identifies citrate\u2010dependent activation of acetyl\u2010CoA carboxylase as a driver of renal lipid accumulation and remodeling independently of AMP\u2010activated protein kinase, revealing a novel metabolic mechanism linking systemic citrate to kidney injury and potential therapeutic strategies.<\/jats:p>\n                  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