The Single-cell Atlas of Short-chain Fatty Acid Receptors in Human and Mice Hearts

Abstract

Abstract The short-chain fatty acids (SCFAs), the product of dietary fiber fermentation by the gut microbiota, can protect against multiple cardiovascular diseases, while the molecular targets and underlying mechanisms need to be elucidated. One of the primary mechanisms of SCFA benefits was the direct activation of a group of G-protein-coupled receptors (GPCRs), termed free fatty acid receptors (FFARs), the FFAR2 (GPR43), and FFAR3 (GPR41). GPCRs serve as key regulators of a variety of intracellular responses and enable the design of highly selective novel drugs with reduced unwanted side effects. This needs an understanding of the heterogeneous distribution of GPCRs across multiple cell types and their overlapping signaling networks. At present, the distribution of FFAR2/3 in cardiac cells has not been entirely clarified. Using the public single-cell RNA-seq and single-nuclear RNA-seq data of human and mouse hearts, we illustrate the entire atlas of FFAR2/3 distribution in different regions and cell types in normal and infarcted hearts. These findings provide valuable information on the possible effect of SCFAs via FFAR2/3 in the heart and valuable references for future studies.