Impact of Short-Chain Fatty Acids on Glucose, Fatty Acid and Leucine Metabolism in Primary Human Myotubes

Short-chain fatty acids (SCFAs) are small molecule metabolites mainly produced during microbial fermentation of dietary fibre in the gut and have been shown to have a beneficial impact on human health. The aim of this study was to evaluate the effect of SCFAs on human skeletal muscle energy metabolism.

Primary human myotubes were analysed for glucose and fatty acid (oleic acid) metabolism, as well as insulin sensitivity and protein synthesis in the presence or absence of SCFAs.

The most pronounced effects of SCFAs were observed on ¹⁴C-oleic acid uptake and oxidation, as well as ¹⁴C-leucine uptake and protein synthesis, following butyrate treatment. Butyrate increased ¹⁴C-leucine accumulation twofold, potentially due to protein incorporation. On the other hand, the conversion of ¹⁴C-leucine into free fatty acids was reduced by more than 50% by butyrate. Both ¹⁴C-acetate and ¹⁴C-butyrate were shown to be taken up and utilised by primary human myotubes. None of the SCFAs were found to influence glucose metabolism or insulin effects.

The results from the current study thus suggest that among the SCFAs, butyrate emerges as the most powerful SCFA in regulating primary human myotube metabolism.