Dihydromyricetin improves colonic mucosal barrier function in mice with metabolism-associated fatty liver disease

Abstract

Objective To investigate the ameliorative effects of dihydromyricetin (DHM) on metabolism-associated fatty liver disease (MAFLD), and to reveal the mechanism of its regulation of intestinal mucosal barrier function. Methods Thirty-two male C57BL/6J mice were randomly divided into 4 groups (n=8): CON (control diet, with 10% fat) group, HFD (high-fat diet, with 45% fat) group, HFD+DHM (high-fat diet+0.6% DHM) group, and DHM (control diet+0.6% DHM) group.All the subjects were intervened for 12 weeks, the body weight and food consumption of mice were measured weekly.Fasting blood glucose, glucose tolerance and intestinal permeability were tested before sacrifice.Serum levels of biochemical indexes and lipopolysaccharide (LPS) were detected with corresponding kits.The liver tissues were stained with HE and oil red O staining, respectively, and the histopathological changes were observed.Moreover, RT-qPCR and Western blotting were used to measure the expression levels of intestinal epithelial tight junction proteins, antimicrobial peptides and liver inflammatory factors.Flow cytometry was adopted to determine the proportion of group 3 innate lymphoid cells (ILC3) and the level of IL-22 in the colon. Results As compared with the CON group, the HFD group presented increased body weight, impaired glucose tolerance, as well as elevated serum total cholesterol, triglyceride, alanine transaminase and aspartate transaminase.HFD also led to liver lipid deposition and higher mRNA levels of IL-1β, IL-6 and TNF-α in the liver.The intestinal permeability and serum LPS were increased, whereas the expression levels of tight junction proteins ZO-1 and Occludin and antimicrobial peptides RegⅢ β and RegⅢ γ in the intestinal mucosa were decreased, and the proportions of ILC3 and IL-22+ ILC3 in the colon were declined (P < 0.05).In the HFD+DHM group, the impaired glucose tolerance was significantly improved, the hepatic lipid deposition and the expression of inflammatory factors were reduced, so was the serum LPS level.DHM also upregulated the levels of intestinal tight junction proteins and antimicrobial peptides, and ameliorated the intestinal permeability.Furthermore, the colonic ILC3 and IL-22+ ILC3 ratios were increased by DHM treatment as well (P < 0.05). Conclusion DHM may ameliorate the progression of MAFLD by improving intestinal barrier function to reduce lipid accumulation and inflammatory responses in the liver.

Keywords

• dihydromyricetin
• metabolism-related fatty liver disease
• intestinal mucosal barrier
• intestinal epithelial cells
• group 3 innate lymphoid cells