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

• Applicant: Dr. Karolin Piepelow
• Subject Area: Nutritional Sciences
• Term: from 2018 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 405898524

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.

• DFG Programme: Research Grants