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.

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

doi:10.3389/fphys.2019.01430

Abstract

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.

Highlights

Fish, the carnivorous species have limited capability of using carbohydrate as energy sources (Hemre et al, 2002; Gong et al, 2015)
Based on the data of weight gain rate (WGR), the optimal dietary bile acids (BA) level based on an 18.7% starch inclusion diet for largemouth bass was 475 mg/kg when estimated by monistic cubic equation regression analysis (Figure 1)
The results of the present study indicated that dietary BA inhibited gluconeogenesis to improve glucose homeostasis and reduced lipogenesis to prevent lipid accumulation of the largemouth bass fed with 18.7% starch inclusion diets

Summary

Introduction

The carnivorous species have limited capability of using carbohydrate as energy sources (Hemre et al, 2002; Gong et al, 2015). The poor adaptation to high dietary carbohydrate loads in carnivorous fish may induce glycogen accumulation in liver tissue and further initiate glucose and lipid metabolic disorder in fish (Amoah et al, 2008; Yu et al, 2018). High dietary digestible carbohydrate induced prevalent metabolic liver disease (MLD) in largemouth bass. Previous studies suggested that the starch (the main source of digestible carbohydrate in aquafeeds) inclusion level in the diet should be lower than 10% to ensure the liver health of largemouth bass (Xu et al, 2016; Ma et al, 2019). Low-starch inclusion leads to increased feed costs and processing energy consumption

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Discussion

Conclusion