Investigating the Acute Effects of Dietary Short-chain and Medium-chain Fatty Acids on Glucose Metabolism, Energy Balance, and Circulating Factors

• Applicant: Professor Maximilian Kleinert, Ph.D.
• Subject Area: Endocrinology, Diabetology, Metabolism ; Nutritional Sciences
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 578455552

Dietary medium-chain fatty acids (MCFAs) have been found to be beneficial for blood sugar levels, cholesterol, and energy balance, even helping with weight loss. However, how exactly they achieve these benefits has remained unclear. In a recent project supported by the DFG, we explored the idea that MCFAs, which are mostly absorbed directly into the liver as free fatty acids, trigger the release of specific proteins called hepatokines. These hepatokines then coordinate the systemic benefits throughout the body. Our team discovered that consuming MCFAs increases the levels of two important proteins in both the liver and bloodstream: growth/differentiation factor 15 (GDF15) and fibroblast growth factor 21 (FGF21). These proteins are crucial for the full effects of MCFAs on reducing appetite and lowering liver fat. We also found other potential hepatokines that might be regulated by MCFAs, but whether these proteins work similarly in humans is an important question to explore. Additionally, we developed a new method to increase the amounts of MCFAs and short-chain fatty acids (SCFAs) in milk fat. When people consume this enhanced milk fat, it increases ketone bodies in their bloodstream, boosts energy expenditure, and helps control blood sugar levels after meals. Although similar benefits have been seen with pure MCFA oils, the effects from our method were notable because the amounts of MCFAs and SCFAs consumed were relatively low. This finding has motivated us to study whether combining dietary intake of both MCFAs and SCFAs can lead to even greater health benefits, potentially offering a new approach to treating metabolic diseases. Building on our previous findings, we are now looking for funding to conduct studies in humans and mice that will examine how circulating metabolites, certain potential hepatokines, blood sugar, insulin, ketone bodies, satiety (feeling full), and energy expenditure change after consuming SCFAs, MCFAs, or both. These studies aim to provide new insights into how these compounds affect metabolism and overall health.

• DFG Programme: Research Grants