Abstract
Fermentation of dietary fibers by colonic microbiota generates short-chain fatty acids (SCFAs), e.g., propionic acid and butyric acid, which have been described to have “anti-obesity properties” by ameliorating fasting glycaemia, body weight and insulin tolerance in animal models. In the present study, we therefore investigate if propionic acid and butyric acid have effects on lipolysis, de novo lipogenesis and glucose uptake in primary rat adipocytes. We show that both propionic acid and butyric acid inhibit isoproterenol- and adenosine deaminase-stimulated lipolysis as well as isoproterenol-stimulated lipolysis in the presence of a phosphodiesterase (PDE3) inhibitor. In addition, we show that propionic acid and butyric acid inhibit basal and insulin-stimulated de novo lipogenesis, which is associated with increased phosphorylation and thus inhibition of acetyl CoA carboxylase, a rate-limiting enzyme in fatty acid synthesis. Furthermore, we show that propionic acid and butyric acid increase insulin-stimulated glucose uptake. To conclude, our study shows that SCFAs have effects on fat storage and mobilization as well as glucose uptake in rat primary adipocytes. Thus, the SCFAs might contribute to healthier adipocytes and subsequently also to improved energy metabolism with for example less circulating free fatty acids, which is beneficial in the context of obesity and type 2 diabetes.
Abbreviations:
- AMPK, AMP-activated protein kinase
- ACC, acetyl-CoA carboxylase
- ADA, adenosine deaminase
- BA, butyric acid
- BSA, bovine serum albumin
- FFAR, free fatty acid receptor
- GLUT, glucose transporter
- GPCR, G-protein-coupled receptor
- HSL, hormone-sensitive lipase
- ISO, isoproterenol
- KRBH, Krebs-Ringer bicarbonate-HEPES
- KRH, Krebs Ringer-HEPES
- PA, propionic acid
- PDE, cyclic nucleotide phosphodiesterase
- SCFAs, short-chain fatty acids
- T2D, type 2 diabetes
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Acknowledgments
Eva Ohlson is acknowledged for her excellent technical assistance.
Funding
The study was financially supported by the Antidiabetic Food Center (AFC), a VINNOVA VINN Excellence Center at Lund University.
Author Contributions
All authors contributed to the design of the study and manuscript writing. EH contributed to the conduct of the study and data collection, whereas all authors contributed with analysis as well as data interpretation.