PubMed · 6794014
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W Lutz. 1980-12-29. [Sphingolipidosis].. https://pubmed.ncbi.nlm.nih.gov/6794014/
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Ceramides (Cer) are bioactive lipids implicated in cardiovascular disease (CVD), yet their subtype-specific causal effects remain unclear. We performed a two-sample Mendelian randomization (MR) analysis using publicly available GWAS summary statistics to investigate the effects of C16:0-ceramide homologs (Cer16:0) and C24:1-ceramide homologs (Cer24:1) on six CVD outcomes. Instrumental variables were rigorously selected, and multiple MR methods were applied to ensure robust inference. Univariable MR identified a significant inverse association between Cer(d18:1/24:1) and heart failure (HF), which remained significant after false discovery rate correction. In contrast, the association for Cer(d17:1/16:0) did not remain significant after correction. No causal associations were observed for other CVD outcomes. When aggregating subtypes, genetically predicted higher total Cer16:0 levels were associated with increased HF risk, while no significant association was found for total Cer24:1. Multivariable MR further demonstrated that the protective effect of Cer(d18:1/24:1) on HF was robust, while estimates for C16 subtypes were attenuated and sensitive to model specification. In conclusion, our findings support a stable protective role of Cer(d18:1/24:1) in HF and highlight the complexity of subtype-specific effects among structurally related ceramides. These results underscore the importance of considering ceramide heterogeneity in cardiovascular research. Further studies are warranted to validate these findings and explore their clinical implications.
The extractable lipids of the gram-negative, sea-water bacterium Cyclobacterium marinus strain WH contain about 94% of polar components which consist of two phospholipids, phosphatidylethanolamine (29% of the total lipids) and phosphatidylcholine (7%), and two phosphorus-free lipids. One of the latter has been shown to be a novel sulfonic-acid analogue of ceramide, 2-D-(2'-D-hydroxy-13'-methyltetradecanoyl) amino-3-D-hydroxy-15-methylhexadec-4 (E)-en-1-sulfonic acid (48%), and other is a lipodipeptide, N-[3-d-(13'-methyltetradecanoyloxy)-15-methylhexadecanoyl] glycyl-L-serine (11%), which has so far been found only in a Flavobacterium sp. strain. The dominant fatty acid residues of the phospholipids are iso-15:0, n-16:0, 16:1 and 18:1, the acyl residues linked to the sn-1 carbon of the glycerol moiety being somewhat more saturated as compared with those located at the sn-2 position. A new procedure for determination of the absolute configuration of 2- and 3-hydroxy fatty acids is briefly described.
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