Targeted Lipidomic and Transcriptomic Analysis Identifies Dysregulated Renal Ceramide Metabolism in a Mouse Model of Diabetic Kidney Disease.

Fri, 2016-06-24 12:01 -- voskuhlt
TitleTargeted Lipidomic and Transcriptomic Analysis Identifies Dysregulated Renal Ceramide Metabolism in a Mouse Model of Diabetic Kidney Disease.
Publication TypeJournal Article
Year of Publication2015
AuthorsSas KM, Nair V, Byun J, Kayampilly P, Zhang H, Saha J, Brosius FC, Kretzler M, Pennathur S
JournalJ Proteomics Bioinform
VolumeSuppl 14
Date Published2015 Oct
ISSN0974-276X
Abstract

Both type 1 and type 2 diabetes are associated with altered lipid metabolism, which might in part contribute to debilitating complications such as diabetic kidney disease (DKD). Ceramides are bioactive sphingolipids that have been implicated in a variety of diseases as they can regulate cellular responses to stress and invoke a myriad of downstream signaling responses. To investigate a potential role of altered ceramide metabolism in DKD, we utilized a highly sensitive and specific mass spectrometry (MS) method to quantitatively measure species in plasma and kidney cortex from the C57BLKS db/db mouse model of DKD and littermate controls. Long-chain ceramides (C14:0, C16:0, C18:0, C20:0) and a glucosylceramide (Glu-Cer C18:0) were increased in diabetic mouse plasma, while long-chain (C14:0, C16:0, C18:0) and very-long-chain (C24:0, C24:1) ceramides and a glucosylceramide (Glu-Cer C16:0) were decreased in diabetic mouse kidney tissue. Kidney and plasma ceramide levels correlated to functional and histopathological features of DKD. Transcriptomic analysis of mouse kidney tissue revealed expression changes indicative of decreased ceramide synthesis (Degs2, Smpd2) and increased conversion to sphingosine (Acer2) and downstream sphingosine-1-phosphate signaling. Correlation analysis identified a negative relationship between plasma and kidney tissue levels of ceramide C16:0 and ceramide C24:1. Overall, the findings suggest a previously unrecognized role for ceramide metabolism in DKD.

DOI10.4172/jpb.S14-002
Alternate JournalJ Proteomics Bioinform
PubMed ID26778897
PubMed Central IDPMC4712744
Grant ListDP3 DK094292 / DK / NIDDK NIH HHS / United States
P30 DK081943 / DK / NIDDK NIH HHS / United States
P30 DK089503 / DK / NIDDK NIH HHS / United States
R24 DK082841 / DK / NIDDK NIH HHS / United States
U24 DK097153 / DK / NIDDK NIH HHS / United States