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

Xiaojun He ^1,2 Qiang Wang ² Qiang Long ¹ Yiming Zhong ¹ Zhaoxi Qi ¹ Yecen Zhang ¹ Lan Chang ¹ Bei Qian ¹ Shixing Huang ¹ Xinming Wang ¹ Xuemei Chen ³ Feifei Li ⁴ Xiaomei Yang ^5,6,7 Wei Dong Gao ⁸ Zhizhao Song ² Li Xu ⁹ Qiang Zhao ^1*

• ¹ Department of Cardiovascular Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
• ² Cardiovascular Medical Center, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
• ³ Department of Anesthesiology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, Shanghai Municipality, China
• ⁴ Department of Cardiology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, Shanghai Municipality, China
• ⁵ Department of Anesthesiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China
• ⁶ School of Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China
• ⁷ Department of Cardiology, Johns Hopkins School of Medicine, Baltimore, Maryland, United States
• ⁸ Department of Anesthesiology & Critical Care Medicine, School of Medicine, Johns Hopkins Medicine, Baltimore, Maryland, United States
• ⁹ Clinical Trial Institution, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China

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.