{Reference Type}: Journal Article {Title}: Single Cell Transcriptomic Analysis Revealed the Cell Populations Changes and Cell-Cell Communication in the Liver of a Carnivorous Fish Response to High Carbohydrate Diet. {Author}: Xie S;Xu J;Chen L;Qi Y;Yang H;Tan B; {Journal}: J Nutr {Volume}: 0 {Issue}: 0 {Year}: 2024 Jun 28 {Factor}: 4.687 {DOI}: 10.1016/j.tjnut.2024.06.016 {Abstract}: BACKGROUND: Carnivorous fish have a low carbohydrate utilization ability, and the physiological and molecular basis of glucose intolerance has not been fully illustrated.
OBJECTIVE: This study aimed to use largemouth bass as a model to investigate the possible mechanism of glucose intolerance in carnivorous fish with the help of snRNA-seq.
METHODS: Two diets were formulated, a low carbohydrate diet (LC) and a high carbohydrate diet (HC). The feeding trial lasted for six weeks, then growth performance, biochemical parameters, liver histology, and snRNA-seq were performed.
RESULTS: Growth performance of fish was not affected by the HC diet, while liver glucolipid metabolism disorder and liver injury were observed. A total of 13247 and 12848 cells from the liver derived from two groups were isolated and sequenced, and 7 major liver cell types were annotated by the marker genes. Hepatocytes and cholangiocytes were lower, hepatic stellate cells (HSCs) and immune cells were higher in the HC group compared to the LC group. Re-clustering analysis identified 7 subtypes of hepatocytes and immune cells, respectively. The HSCs showed more cell communication with other cell types, and periportal hepatocytes showed more cell communication with other subtype hepatocytes. Cell-cell communication mainly focused on cell junction related signaling pathways. Uncovered by the pseudotime analysis, midzonal hepatocytes were differentiated into two major branches, biliary epithelial hepatocytes, and hepatobiliary hybrid progenitor. Cell junction and liver fibrosis related genes were highly expressed in HC group, HC diet induced the activation of HSCs, and therefore led to the liver fibrosis of largemouth bass.
CONCLUSIONS: HC diet induced liver glucolipid metabolism disorder and liver injury of largemouth bass,the increase and activation of HSCs might be the main reason for the liver injury. In adaption to HC diet, midzonal hepatocytes differentiated into two major branches, biliary epithelial hepatocytes, and hepatobiliary hybrid progenitors.