Dietary inulin decreases circulating ceramides by suppressing neutral sphingomyelinase expression and activity in mice

Pan Deng, Jessie B. Hoffman, Michael C. Petriello, Chun Yan Wang, Xu Sheng Li, Maria P. Kraemer, Andrew J. Morris, Bernhard Hennig

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Elevated circulating levels of ceramides (Cers) are associated with increased risk of cardiometabolic diseases, and Cers may play a causative role in metabolic dysfunction that precedes cardiac events, such as mortality as a result of coronary artery disease. Although the mechanisms involved are likely complex, these associations suggest that lowering circulating Cer levels could be protective against cardiovascular diseases. Conversely, dietary fibers, such as inulin, have been reported to promote cardiovascular and metabolic health. However, the mechanisms involved in these protective processes also are not well understood. We studied the effects of inulin on lipid metabolism with a model of atherosclerosis in LDL receptor-deficient mice using lipidomics and transcriptomics. Plasma and tissues were collected at 10 days and/or 12 weeks after feeding mice an atherogenic diet supplemented with inulin or cellulose (control). Compared with controls, inulin-fed mice displayed a decreased C16:0/C24:0 plasma Cer ratio and lower levels of circulating Cers associated with VLDL and LDL. Liver transcriptomic analysis revealed that Smpd3, a gene that encodes neutral SMase (NSMase), was downregulated by 2-fold in inulin-fed mice. Hepatic NSMase activity was 3-fold lower in inulin-fed mice than in controls. Furthermore, liver redox status and compositions of phosphatidylserine and FFA species, the major factors that determine NSMase activity, were also modified by inulin. Taken together, these results showed that, in mice, inulin can decrease plasma Cer levels through reductions in NSMase expression and activity, suggesting a mechanism by which fiber could reduce cardiometabolic disease risk.

Original languageEnglish
Pages (from-to)45-53
Number of pages9
JournalJournal of Lipid Research
Volume61
Issue number1
DOIs
StatePublished - 2020

Bibliographical note

Publisher Copyright:
© 2020 American Society for Biochemistry and Molecular Biology Inc.. All rights reserved.

Keywords

  • Fiber
  • Lipidomics
  • Transcriptomics

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Dietary inulin decreases circulating ceramides by suppressing neutral sphingomyelinase expression and activity in mice'. Together they form a unique fingerprint.

Cite this