Inhibition Of Liver Steatosis In Zebrafish Under Simulated Dark Breeding Conditions With The Mongolian Medicine Yihe-Tang

Constant darkness(DD)induces hepatic lipid degeneration and non-alcoholic fatty liver disease(NAFLD)in zebrafish,which may be closely related to the imbalance of intestinal flora and needs to be studied in depth.The goal of our study is to test whether Yihe-Tang targets from the intestinal-liver axis,and to explore the mechanism of action of Yihe-Tang in the treatment of NAFLD from the perspective of intestinal flora balance,which will lay the theoretical foundation for the regulation of the intestinal-liver axis.In this study,144 zebrafish were divided into 4 groups: Control group,Yihe-Tang group,constan dark group,and constant dark + Yihe-Tang group,and were given dark treatment for 21 d.The body weights of zebrafish were recorded at 8 d,15 d and 22 d,respectively,and samples were collected on day 22 of the experiment for gut flora sequencing analysis,detection of histopathological changes in the liver,and detection of gene expression related to lipid metabolism The results showed that the continuous darkness treatment induced the induction of the gastrointestinal flora.The results showed that constant darkness treatment induced an increase in body weight in zebrafish and that Yihe-Tang inhibited this weight gain and suppressed liver steatosis.Gene level studies showed that constant darkness treatment also resulted in significant up-regulation of lipid synthesis-related genes,fasn,and down-regulation of lipid synthesis-related genes,cpt1 and acadm,in the liver of zebrafish,while Yihe-Tang treatment restored the expression of various genes,almost to normal group levels.Constant darkness was able to alter the composition of the zebrafish gut flora.21 d Constant darkness increased the relative abundance of harmful bacteria in the zebrafish gut flora and reduced the proportion of Cetobacterium,Bacteroides and Firmicutes in the gut.In contrast,the Yihe-Tang treatment restored the abundance of Proteobacteria to the tract Control level,and Yihe-Tang also increased the abundance of Clostridium spp.(Fusobacteria)and Cetobacterium,with the increase in Cetobacterium being particularly pronounced.The experimental results showed that constant darkness treatment led to abnormal expression of hepatic lipid-related genes,inhibiting lipid metabolism,promoting lipid accumulation and causing steatosis.In contrast,Yihe-Tang restored these changes to control levels.This may be closely related to the changes in the gut microbiota.