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日粮中胆汁酸通过AKT/FOXO1和cAMP/AMPK/SREBP1信号通路促进大口黑鲈生长，缓解高淀粉日粮诱导的肝纤维化

Dietary bile acids enhance growth, and alleviate hepatic fibrosis induced by a high starch diet via AKT FOXO1 and cAMP AMPK SREBP1 pathway in Micropterus salmoides

作者：Huanhuan Yu, Lulu Zhang, Pei Chen, Xiaofang Liang, Aizhi Cao, Juan Han, Xiufeng Wu, Yinhua Zheng, Yuchang Qin, Min Xue.

发布期刊：Front Physiol. 2019 Nov 19;10:1430.

在为期10周的饲养试验中，研究了高淀粉饵料中添加胆汁酸对大口黑鲈（Micropterus salmoides）的生长性能、葡萄糖和脂质代谢、肝脏组织病理学以及AKT/FOXO1（forkhead box O1）和cAMP/AMPK/SREBP1（sterol regulatory element-binding protein 1）信号通路的调节机制。根据18.7%淀粉的基础饵料制备了6种试验饵料，胆汁酸水平分别为0、80、160、240、300和600 mg/kg。每个处理组6个重复，每个重复30尾鱼（6.17±0.03g）。胆汁酸300组观察到最高的增重率（WGR），通过单因素方差分析确定胆汁酸的最佳量为475mg/kg。饵料中胆汁酸的添加显著降低了肝重指数（HSI）和肝脏脂肪含量。胆汁酸300组的鱼类明显减轻了肝纤维化，但在各种组织病理学和免疫荧光分析中更多地诊断出脂肪肝炎症状。在胆汁酸0组中，12个样本中有10个观察到肝纤维化，而在胆汁酸300组中仅有2个纤维化样本。日粮中胆汁酸的促进肝脏病理学与改善葡萄糖和脂质代谢有关。日粮中的胆汁酸通过激活AKT和降低FOXO1的转录来抑制G6Pase的表达，从而改善了糖异生的调节能力，激活cAMP/AMPK并抑制SREBP1的转录，来抑制肝脏脂肪合成，防止肝脏脂质积累。总之，日粮中的胆汁酸通过改善葡萄糖和脂质代谢，调节AKT/FOXO1和cAMP/AMPK/SREBP1信号通路，在高淀粉饵料下增强了大口黑鲈的生长并减轻了肝纤维化，改善脂肪肝炎/恢复症状。

A 10-week feeding trial was conducted to investigate the effects of dietary bile acids (BA) on growth, glucose and lipid metabolism, liver histopathology, and the underlying regulation mechanism on AKT/FOXO1 (forkhead box O1) and cAMP/AMPK/SREBP1 (sterol regulatory element-binding protein 1) pathway in largemouth bass (Micropterus salmoides) fed with a high starch diet. Six experimental diets were prepared with BA levels at 0 (B0), 80 (B80), 160 (B160), 240 (B240), 300 (B300), and 600 (B600) mg/kg in a basal diet with 18.7% starch. Each diet was fed to six replicates with 30 fish (6.17 ± 0.03 g) in each tank. The highest weight gain rate (WGR) was observed in B300 group and the optimal level of BA was estimated at 475 mg/kg by a monistic cubic equation regression analysis. Dietary BA inclusion decreased hepatosomatic index (HSI) and hepatic lipid content significantly. The fish in B300 group clearly showed alleviated hepatic fibrosis, but more steatohepatitis symptoms diagnosed with various histopathological and immunofluorescence analysis. 10 out of 12 samples were observed hepatic fibrosis in B0 group while only two fibrosis samples in B300 group. The promoted liver histopathology by dietary BA was related to improved glucose and lipid metabolism. Dietary BA inhibited the expression of G6Pase by activating AKT and reducing FOXO1 transcription, which improved the regulation ability of gluconeogenesis, activated cAMP/AMPK and repressed SREBP1 transcription to inhibit hepatic lipogenesis, which prevented hepatic lipid accumulation. In conclusion, dietary BA enhanced the growth and alleviated liver fibrosis induced by a high starch diet to steatohepatitis/recovery symptom via improving glucose and lipid metabolism, which regulated by AKT/FOXO1 and cAMP/AMPK/SREBP1 pathway in largemouth bass.

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