The health benefits of dietary short-chain fatty acids in metabolic diseases

Short-chain fatty acids (SCFAs) are a subset of fatty acids that play crucial roles in maintaining normal physiology and developing metabolic diseases, such as obesity, diabetes, cardiovascular disease, and liver disease. Even though dairy products and vegetable oils are the direct dietary sources of SCFAs, their quantities are highly restricted. SCFAs are produced indirectly through microbial fermentation of fibers. The biological roles of SCFAs in human health and metabolic diseases are mainly due to their receptors, GPR41 and GPR43, FFAR2 and FFAR3. Additionally, it has been demonstrated that SCFAs modulate DNMTs and HDAC activities, inhibit NF-κB-STAT signaling, and regulate G(i/o)βγ-PLC-PKC-PTEN signaling and PPARγ-UCP2-AMPK autophagic signaling, thus mitigating metabolic diseases. Recent studies have uncovered that SCFAs play crucial roles in epigenetic modifications of DNAs, RNAs, and post-translational modifications of proteins, which are critical regulators of metabolic health and diseases. At the same time, dietary recommendations for the purpose of SCFAs have been proposed. The objective of the review is to summarize the most recent research on the role of dietary SCFAs in metabolic diseases, especially the signal transduction of SCFAs in metabolic diseases and their functional efficacy in different backgrounds and models of metabolic diseases, at the same time, to provide dietary and nutritional recommendations for using SCFAs as food ingredients to prevent metabolic diseases.