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

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: acetate; butyrate; energy metabolism; leucine; myotubes; propionate; protein synthesis; short‐chain fatty acids.