Roles of short-chain fatty acids in metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis

Figure 2 Graphic demonstration of the role of short-chain fatty acids in CD8⁺ T cells and Tregs during metabolic dysfunction-associated steatotic liver disease/metabolic dysfunction-associated steatohepatitis. Short-chain fatty acids (SCFAs) bind with receptor free fatty acid receptor 2 on hepatocytes to enhance insulin sensitivity. SCFAs support memory CD8⁺ T cell survival and maintenance and accelerate the apoptosis of activated hepatic stellate cells. SCFAs increase the number of Tregs and IL-10⁺ effector Tregs in metabolic dysfunction-associated steatohepatitis (MASH)-hepatocellular carcinoma. SCFAs promote the conversion of CXCR6⁺ CD8 T cells to cytotoxic auto-aggressive CD8⁺ T cells in MASH. SCFA: Short-chain fatty acid; FFAR2: Free fatty acid receptor 2; HSC: Hepatic stellate cells; MASH: Metabolic dysfunction-associated steatohepatitis; MASLD: Metabolic dysfunction-associated steatotic liver disease; HCC: Hepatocellular carcinoma. This figure was created using BioRender.com (Supplementary material).