Nonalcoholic fatty liver disease and cirrhosis are strongly associated with insulin resistance and glucose intolerance. To date, the influence of metformin on glycogen synthesis in the liver is controversial. Limited studies have evaluated the effect of metformin on hepatic insulin signaling pathwayin vivo. In this study, an insulin-resistant rat model of nonalcoholic steatohepatitis and cirrhosis was developed by high-fat and high-sucrose diet feeding in combination with subcutaneous injection of carbon tetrachloride. Liver tissues of the model rats were featured with severe steatosis and cirrhosis, accompanied by impaired liver function and antioxidant capacity. The glucose tolerance was impaired, and the index of insulin resistance was increased significantly compared with the control. The content of hepatic glycogen was dramatically decreased. The expression of insulin receptor β (IRβ); phosphorylations of IRβ, insulin receptor substrate 2 (IRS2), and Akt; and activities of phosphatidylinositol 3-kinase (PI3K) and glycogen synthase (GS) in the liver were significantly decreased, whereas the activities of glycogen synthase kinase 3α (GSK3α) and glycogen phosphorylase a (GPa) were increased. Metformin treatment remarkably improved liver function, alleviated lipid peroxidation and histological damages of the liver, and ameliorated glucose intolerance and insulin resistance. Metfromin also significantly upregulated the expression of IRβ; increased the phosphorylations of IRβ, IRS2, and Akt; increased the activities of PI3K and GS; and decreased GSK3α and GPa activities. In conclusion, our study suggests that metformin upregulates IRβ expression and the downstream IRS2/PI3K/Akt signaling transduction, therefore, to increase hepatic glycogen storage and improve insulin resistance. These actions may be attributed to the improved liver histological alterations by metformin.

Stringent non-pharmaceutical measures to contain the COVID-19 outbreak in China also significantly reduced the spread of influenza in the winter season 2020.

Background: Currently, active ingredients of herbal extracts that can suppress lipid accumulation in the liver have been considered a potential treatment option for non-alcoholic fatty liver disease. Methods: Steatosis rat model was created by high fat and high sucrose diet feeding and treated with oxymatrine (OMT). Serum biochemical parameters, liver histology and lipid profiles were examined. Hepatic differentially expressed proteins (DEPs) which were significantly changed by OMT treatment were identified by iTRAQ analysis. The expressions of representative DEPs, Sirt1 and AMPKα were evaluated by western blotting. Results: OMT significantly reduced the body weight and liver weight of steatosis animals, decreased the serum levels of triglyceride and total cholesterol as well as the hepatic triglyceride and free fatty acid levels, and effectively alleviated fatty degeneration in the liver. A list of OMT-related DEPs have been screened and evaluated by bioinformatics analysis. OMT significantly decreased the expressions of L-FABP, Plin2, FASN and SCD1 and increased Sirt1 expression and AMPKα phosphorylation in the liver of rats with steatosis. Conclusion: The present study has confirmed the significant efficacy of OMT for improving steatosis and revealed hepatic proteomic changes and Sirt1/AMPK signaling activation by OMT treatment in rats with steatosis.

Background/Aim: High-fat diets induce shifts in the gut microbial community structure in patients or animals with non-alcoholic steatohepatitis (NASH). The objective of this study was to investigate the influence of metformin (MET) and berberine (BER) on the intestinal microbiota of rats with NASH. Materials and Methods: Forty specific pathogen-free male Sprague-Dawley rats were randomized into 4 groups. Model rats were fed high-fat diets to create NASH models. MET or BER rats were administrated MET or BER, respectively, at the onset of induction of NASH. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol, and triglycerides were examined. Plasma endotoxin levels were measured using the turbidimetric endotoxin assay. The incidence of bacterial translocation describes the passage of bacteria of the gastrointestinal tract through the intestinal mucosa barrier to mesenteric lymph nodes and other organs. Hematoxylin and eosin and oil red O staining were used for histopathological analysis. High throughput 16S rRNA sequencing was carried out for analyzing the composition of intestinal microbiota. Results: High-fat diets caused NASH after 16-week induction. Administration of MET and BER ameliorated NASH by attenuating hepatic steatosis and inflammation and decreasing the plasma levels of endotoxin. MET and BER restored the composition of the intestinal microbiota disrupted by NASH. Both MET and BER altered the abundance of Atopobiaceae, Brevibacterium, Christensenellaceae, Coriobacteriales, Papillibacter, Pygmaiobacter, and Rikenellaceae RC9 in rats with NASH. The screened intestinal microbiota may be responsible for the improvement in fat accumulation and glucose metabolism. Conclusion: MET and BER demonstrated beneficial effects on the intestinal microbiota, which was disturbed in NASH. This finding may explain the functional mechanism of MET and BER in NASH.

Mosapride significantly improves intestinal motility in liver cirrhosis, ultimately leading to the reduction in plasma endotoxin levels and bacterial translocation. To investigate the effects of mosapride on intestinal microecology in cirrhotic rats and its potential mechanisms. Forty-five healthy male Sprague-Dawley rats that were pathogen-free (weight 200-220 g) were randomly divided into a control group (n = 15), model group (n = 15) and mosapride group (n = 15). Then, the pathological changes in the liver and intestine were determined through tissue staining and using transmission electron microscope (TEM). Bacterial translocation was examined. High throughput 16S rRNA sequencing was performed to determine the changes of gut microbiota in each group. Compared with the model group, mosapride treatment induced no attenuation in hepatic morphology and pathology changes. The TEM indicated no differences in intestinal structure in both groups. There was a significant decline in the rate of gut microbiota translocation in the mosapride group compared with the model group. There were intestinal microbiota changes in the mosapride group compared with that of the model group, including Bacteroidetes, Prevotellaceae, Alloprevotella, Ruminiclostridium, Negativicutes, Selenomonadales, Veillonellaceae, Anaerovibrio, Campylobacterales, Epsilonbacteraeota, Helicobacter, Oscillibacter, Verrucomicrobiales, Akkermansia, Intestinimonas, Eubacterium, Clostridiaceae, Clostridium, Bacteroides, Tyzzerella, Actinobacteria, and Bifidobacteriales. Among these bacteria, Alloprevotella showed a strong correlation with the other bacteria. Taken together, we concluded that mosapride may reduce intestinal bacterial translocation through regulating the gut microbiota in rats with hepatic cirrhosis.

A polysaccharide LDOP‐A with a molecular weight of 9.9 kDa was isolated and purified from Dendrobium officinale leaves by membrane separation, cellulose column, and dextran gel column. The Smith degradable products, methylation products, and nuclear magnetic resonance analysis showed that LDOP‐A may be composed of →4)‐Glc‐(1→, →3,6)‐Man‐(1→, and →6)‐Glc‐(1→sugar residues. In vitro, simulated digestion assays showed that LDOP‐A could be partially digested in the stomach and small intestine, and produced a large amount of acetic acid and butyric acid during colonic fermentation. Further cell experiment results illustrated that LDOP‐A‐I (LDOP‐A digested by gastrointestinal tract) could induce glucagon‐like peptide‐1 (GLP‐1) secretion in NCI‐H716 cells without showing any cytotoxicity.