Lopes-Virella Maria F, Hammad Samar M, Baker Nathaniel L, Klein Richard L, Hunt Kelly J
Department of Medicine, Division of Diabetes, Endocrinology and Medical Genetics, Medical University of South Carolina, Charleston, SC 29425, USA.
Ralph H. Johnson VA Medical Center, Charleston, SC 29401, USA.
Biomedicines. 2024 Jan 15;12(1):190. doi: 10.3390/biomedicines12010190.
Abnormalities of sphingolipid metabolism play an important role in diabetes. We compared sphingolipid levels in plasma and in isolated lipoproteins between healthy control subjects and two groups of patients, one with chronic kidney disease without diabetes (ND-CKD), and the other with type 2 diabetes and macroalbuminuria (D-MA). Ceramides, sphingomyelins, and sphingoid bases and their phosphates in LDL were higher in ND-CKD and in D-MA patients compared to controls. However, ceramides and sphingoid bases in HDL2 and HDL3 were lower in ND-CKD and in D-MA patients than in controls. Sphingomyelins in HDL2 and HDL3 were lower in D-MA patients than in controls but were normal in ND-CKD patients. Compared to controls, lactosylceramides in LDL and VLDL were higher in ND-CKD patients but not in D-MA patients. However, lactosylceramides in HDL2 and HDL3 were lower in both ND-CKD and D-MA patients than in controls. Plasma hexosylceramides in ND-CKD patients were increased and sphingoid bases decreased in both ND-CKD and D-MA patients. However, hexosylceramides in LDL, HDL2, and HDL3 were higher in ND-CKD patients than in controls. In D-MA patients, only C16:0 hexosylceramide in LDL was higher than in controls. The data suggest that sphingolipid measurement in lipoproteins, rather than in whole plasma, is crucial to decipher the role of sphingolipids in kidney disease.
鞘脂代谢异常在糖尿病中起重要作用。我们比较了健康对照受试者与两组患者（一组为无糖尿病的慢性肾脏病患者（ND-CKD），另一组为2型糖尿病伴大量蛋白尿患者（D-MA））血浆及分离出的脂蛋白中的鞘脂水平。与对照组相比，ND-CKD组和D-MA组患者低密度脂蛋白（LDL）中的神经酰胺、鞘磷脂、鞘氨醇及其磷酸盐含量更高。然而，ND-CKD组和D-MA组患者高密度脂蛋白2（HDL2）和高密度脂蛋白3（HDL3）中的神经酰胺和鞘氨醇含量低于对照组。D-MA组患者HDL2和HDL3中的鞘磷脂含量低于对照组，但ND-CKD组患者的鞘磷脂含量正常。与对照组相比，ND-CKD组患者LDL和极低密度脂蛋白（VLDL）中的乳糖神经酰胺含量更高，但D-MA组患者并非如此。然而，ND-CKD组和D-MA组患者HDL2和HDL3中的乳糖神经酰胺含量均低于对照组。ND-CKD组患者血浆己糖神经酰胺增加，ND-CKD组和D-MA组患者的鞘氨醇均减少。然而，ND-CKD组患者LDL、HDL2和HDL3中的己糖神经酰胺含量高于对照组。在D-MA组患者中，仅LDL中的C16:0己糖神经酰胺含量高于对照组。数据表明，测定脂蛋白而非全血浆中的鞘脂对于解读鞘脂在肾脏疾病中的作用至关重要。
