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.
|Number of pages||9|
|Journal||Journal of Lipid Research|
|State||Published - 2020|
Bibliographical noteFunding Information:
This study was supported in part by the National Institutes of Health/National Institute of Environmental Health Sciences Grant P42ES007380 and National Institutes of Health/National Institute of General Medical Sciences Grants 1S10OD021753 and P30 GM127211. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors declare that they have no conflicts of interest with the contents of this article. Manuscript received 16 August 2019 and in revised form 9 October 2019. Published, JLR Papers in Press, October 11, 2019 DOI https://doi.org/10.1194/jlr.RA119000346
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ASJC Scopus subject areas
- Cell Biology