Circulating Lipoprotein Sphingolipids in Chronic Kidney Disease with and without Diabetes

Author:

Lopes-Virella Maria F.12,Hammad Samar M.3ORCID,Baker Nathaniel L.4,Klein Richard L.12,Hunt Kelly J.24

Affiliation:

1. Department of Medicine, Division of Diabetes, Endocrinology and Medical Genetics, Medical University of South Carolina, Charleston, SC 29425, USA

2. Ralph H. Johnson VA Medical Center, Charleston, SC 29401, USA

3. Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA

4. Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC 29425, USA

Abstract

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.

Funder

NIH/NIDDK

Research Service of the Ralph H. Johnson Department of the Veterans Affairs Medical Center

Lipidomics Shared Resource, Hollings Cancer Center, MUSC

Publisher

MDPI AG

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