Effects of gut metabolites in cell-bioassays
A large body of research indicates that dietary fibers have a profound effect on the regulation of energy homeostasis, weight control and appetite control. These effects appear to be mediated to a large extent by short chain fatty acids (SCFAs) generated from fermentation of dietary fibers, indeed, SCFAs are the main bacterial metabolites of the colonic fermentation process. Acetic acid, propionic acid and butyric acid are the most abundant SCFAs produce, however, the relative amounts of SCFAs generated is influenced by the type of carbohydrates we eat. In addition to acetic acid, propionic acid and butyric acid also branched amino acids are generated during the fermentation process such as isobutyric acid and isovaleric acid. In addition to having effects in the intestine, SCFAs reach the circulation and impact on different tissues in the body. The effects of SCFAs are believed to be mediated via the free fatty acid receptor (FFAR) 2 and 3. In addition, SCFAs are believed to enter cells via specific transporters and can thus bind directly to intracellular targets such as histone deacetylases (HDACs). We focus on the effects of SCFAs on adipose tissue, a key target tissue in the regulation of whole body energy metabolism and a target in the prevention of dysmetabolic states.
To this end, our results show that acute treatment with SCFAs has multiple effects on adipocyte lipid and glucose metabolism. In summary SCFAs decrease lipolysis stimulated by different pathways and basal as well as insulin-stimulated lipogenesis. In addition, SCFAs stimulate insulin-mediated glucose uptake. Inhibition of lipolysis is beneficial in dysmetabolic states, when one is at risk to develop insulin resistance since it prevents the lipotoxic effect of increased levels of circulating fatty acids. Also, inhibition of de novo lipogenesis is beneficial under those conditions since the priority should be to store dietary lipids and not to produce new lipids from other substrates. Finally insulin-mediated glucose uptake is beneficial although not quantitatively important. The beneficial effect is related to the ability of glucose to regulated pathways in adipocytes leading to improved whole body energy homeostasis.
Project leader: Prof Eva Degerman.