Laboratory of Aquatic Nutrition and Feed, College of Fisheries, Guangdong Ocean University, Zhanjiang, PR China; Aquatic Animals Precision Nutrition and High-Efficiency Feed Engineering Research Center of Guangdong Province, Zhanjiang, PR China; Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, PR China; Guangdong Provincial Key Lab of Aquatic Animals Disease Control and Healthy Culture, Zhanjiang, China.
Guangxi Academy of Marine Sciences, Guangxi Academy of Sciences, Nanning, China.
J Nutr. 2024 Aug;154(8):2381-2395. doi: 10.1016/j.tjnut.2024.06.016. Epub 2024 Jun 28.
Carnivorous fish have a low carbohydrate utilization ability, and the physiologic and molecular basis of glucose intolerance has not been fully illustrated.
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 single-nuclei RNA sequencing (snRNA-seq).
Two diets were formulated, a low-carbohydrate (LC) diet and a high-carbohydrate (HC) diet. The feeding trial lasted for 6 wk, and then, growth performance, biochemical parameters, liver histology, and snRNA-seq were performed.
Growth performance of fish was not affected by the HC diet, while liver glucolipid metabolism disorder and liver injury were observed. A total of 13,247 and 12,848 cells from the liver derived from 2 groups were isolated and sequenced, and 7 major liver cell types were annotated by the marker genes. Hepatocytes and cholangiocytes were lower and hepatic stellate cells (HSCs) and immune cells were higher in the HC group than those in the LC group. Reclustering 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 hepatocyte subtypes. Cell-cell communication mainly focused on cell junction-related signaling pathways. Uncovered by the pseudotime analysis, midzonal hepatocytes were differentiated into 2 major branches-biliary epithelial hepatocytes and hepatobiliary hybrid progenitor. Cell junction and liver fibrosis-related genes were highly expressed in the HC group. HC diet induced the activation of HSCs and, therefore, led to the liver fibrosis of largemouth bass.
HC diet induces 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 differentiates into 2 major branches-biliary epithelial hepatocytes and hepatobiliary hybrid progenitors.
肉食性鱼类碳水化合物利用率较低，葡萄糖不耐受的生理和分子基础尚未完全阐明。
本研究以大口黑鲈为模型，借助单细胞 RNA 测序（snRNA-seq）探讨肉食性鱼类葡萄糖不耐受的可能机制。
配制两种饲料，即低碳水化合物（LC）饲料和高碳水化合物（HC）饲料。进行为期 6 周的饲养试验，然后进行生长性能、生化参数、肝脏组织学和 snRNA-seq 检测。
HC 饲料对鱼类的生长性能没有影响，但观察到肝脏糖脂代谢紊乱和肝损伤。从 2 组肝脏中分别分离和测序得到 13247 个和 12848 个细胞，并用标记基因注释了 7 种主要的肝细胞类型。HC 组的肝细胞和胆管细胞较低，肝星状细胞（HSCs）和免疫细胞较高。重聚类分析分别鉴定出 7 种亚型的肝细胞和免疫细胞。HSCs 与其他细胞类型的细胞间通讯较多，门脉周围肝细胞与其他肝细胞亚型的细胞间通讯较多。细胞间通讯主要集中在细胞连接相关的信号通路。伪时间分析未揭示门脉周围肝细胞分化为胆管上皮细胞和肝胆杂交祖细胞的 2 个主要分支。细胞连接和肝纤维化相关基因在 HC 组中高表达。HC 饲料诱导 HSCs 活化，从而导致大口黑鲈的肝纤维化。
HC 饲料诱导大口黑鲈肝脏糖脂代谢紊乱和肝损伤。HSCs 的增加和活化可能是肝损伤的主要原因。在适应 HC 饲料时，门脉周围肝细胞分化为胆管上皮细胞和肝胆杂交祖细胞的 2 个主要分支。
