Role of dietary derived propionyl-CoA in the prevention of obesity-induced health impairments

膳食来源的丙酰辅酶A在预防肥胖引起的健康损害中的作用

• 批准号: 405898524
• 负责人: Dr. Karolin Piepelow
• 金额: --
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/405898524?language=en
• 关键词: Role; dietary; derived; propionyl; CoA

Recent data provide evidence for an improvement of diet-induced hepatic steatosis and insulin resistance by propionate (Pr) which is intestinally produced from fermentable fiber. Correspondingly, odd-chain fatty acids (OCFA) in plasma phospholipids are induced indicating that propionyl-CoA (Pr-CoA) is used for fatty acid synthesis. Beside their consideration as biomarkers for dairy intake, OCFA are related to an improved insulin sensitivity and type 2 diabetes risk. However, causal relationships are not elucidated. Since the detectable amount of OCFA in plasma is low, I hypothesize that beneficial associations are rather a consequence of increased Pr-CoA availability. For drawing causal conclusions I will perform dietary intervention studies in mice to identify by which dietary components metabolic Pr-CoA concentrations are increased by comparing circulating concentrations of Pr, Pr-CoA and OCFA. To systematically examine the causality of metabolic improvements, an additional OCFA-supplemented diet will be used to differentiate between Pr-CoA- and OCFA-mediated health effects. Subsequent analysis of hepatic mechanisms supported by cell culture experiments will be carried out to uncover underlying mechanisms. This project is important to understand how Pr-CoA can change metabolic characteristics and further improve whole body energy metabolism.

最近的数据提供了证据，证明丙酸盐（Pr）可以改善饮食诱导的肝脏脂肪变性和胰岛素抵抗，而丙酸盐是由可发酵纤维代谢产生的。相应地，诱导血浆磷脂中的奇数链脂肪酸（OCFA），表明丙酰辅酶A（Pr-CoA）用于脂肪酸合成。除了被认为是乳制品摄入的生物标志物外，OCFA还与改善胰岛素敏感性和2型糖尿病风险有关。然而，因果关系没有阐明。由于血浆中OCFA的可检测量较低，因此我假设有益的关联是Pr-CoA可用性增加的结果。为了得出因果关系的结论，我将在小鼠中进行饮食干预研究，通过比较Pr，Pr-CoA和OCFA的循环浓度，确定哪些饮食成分代谢Pr-CoA浓度增加。为了系统地检查代谢改善的因果关系，将使用额外的OCFA补充饮食来区分Pr-CoA和OCFA介导的健康影响。随后将对细胞培养实验支持的肝脏机制进行分析，以揭示潜在的机制。该项目对于了解Pr-CoA如何改变代谢特征并进一步改善全身能量代谢非常重要。