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.

中文翻译：

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膳食菊粉通过抑制小鼠中性鞘磷脂酶的表达和活性来减少循环神经酰胺。

神经酰胺（Cers）的循环水平升高与心脏代谢疾病的风险增加相关，并且Cers可能在心脏事件之前的代谢功能异常中起因果作用，例如冠状动脉疾病导致的死亡。尽管所涉及的机制可能很复杂，但这些关联表明降低循环Cer水平可以预防心血管疾病。相反，据报道，膳食纤维（如菊粉）可促进心血管和代谢健康。但是，还没有很好地理解这些保护过程中涉及的机制。我们使用脂质组学和转录组学研究了LDL受体缺陷型小鼠的动脉粥样硬化模型中菊粉对脂质代谢的影响。在给小鼠补充了菊粉或纤维素的致动脉粥样化饮食后10天和/或12周收集血浆和组织。与对照组相比，用菊粉喂养的小鼠显示出降低的C16：0 / C24：0血浆Cer比，并降低了与VLDL和LDL相关的循环Cer水平。肝转录组分析显示菊粉喂养的小鼠中，编码中性SMase（NSMase）的基因Smpd3下调了2倍。菊粉喂养的小鼠的肝NSMase活性比对照组低3倍。此外，菊粉还改善了肝脏氧化还原状态以及磷脂酰丝氨酸和FFA种类的成分，这些因素是决定NSMase活性的主要因素。综上，这些结果表明，在小鼠中，菊粉可以通过降低NSMase表达和活性来降低血浆Cer水平，这表明纤维可以降低心脏代谢疾病的风险。