biostudies-literatureIto SJSPS KAKENHIe179362https://www.ebi.ac.uk/biostudies/studies/S-EPMC12288908biostudies-literatureUnknown10(13)Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease. Kidney tubular cells have a high energy demand, dependent on fatty acid oxidation (FAO). Although carnitine is indispensable for FAO, the pathological role of carnitine deficiency in DKD is not fully understood. We showed here that ectopic lipid accumulation owing to impaired FAO increased in patients with DKD and inversely correlated with kidney function. Organic cation/carnitine transporter 2-deficient (OCTN2-deficient) mice exhibited systemic carnitine deficiency with increased renal lipid accumulation. Cell death and inflammation were induced in OCTN2-deficient, but not wild-type, tubular cells exposed to high salt and high glucose. Compared with Spontaneously Diabetic Torii (SDT) fatty rats, uninephrectomiJCI insightInvolvement of impaired carnitine-induced fatty acid oxidation in experimental and human diabetic kidney disease.PMC1228890818K15990Grant-in-Aid for Young ScientistsYokota YKodama GKaida YTaguchi KTashiro KFukami KYamagishi SIIto SShinohara MOhta KKubo SMoriyama TYamashita YNakayama YfalseInvolvement of impaired carnitine-induced fatty acid oxidation in experimental and human diabetic kidney disease.Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease. Kidney tubular cells have a high energy demand, dependent on fatty acid oxidation (FAO). Although carnitine is indispensable for FAO, the pathological role of carnitine deficiency in DKD is not fully understood. We showed here that ectopic lipid accumulation owing to impaired FAO increased in patients with DKD and inversely correlated with kidney function. Organic cation/carnitine transporter 2-deficient (OCTN2-deficient) mice exhibited systemic carnitine deficiency with increased renal lipid accumulation. Cell death and inflammation were induced in OCTN2-deficient, but not wild-type, tubular cells exposed to high salt and high glucose. Compared with Spontaneously Diabetic Torii (SDT) fatty rats, uninephrectomi2025-01-01T00:00:00Z2025 Jul2026-07-15T12:34:01.61Z2025-08-30T03:05:28.744ZS-EPMC122889084040257810.1172/jci.insight.179362