Protection against Metabolic Associated Fatty Liver Disease by Protocatechuic Acid

Abstract

Gut microbiota–diet interaction has been identified as a key factor of metabolic associated fatty liver disease (MAFLD). Recent studies suggested that dietary polyphenols may protect against MAFLD by regulating gut microbiota; however, the underlying mechanisms remain elusive. We first investigated the effects of cyanidin 3-glucoside and its phenolic metabolites on high-fat diet induced MAFLD in C57BL/6J mice, and protocatechuic acid (PCA) showed a significant positive effect. Next, regulation of PCA on lipid metabolism and gut microbiota were explored by MAFLD mouse model and fecal microbiota transplantation (FMT) experiment. Dietary PCA reduced intraperitoneal and hepatic fat deposition with lower levels of transaminases (AST & ALT) and inflammatory cytokines (IL-1β, IL-2, IL-6, TNF-α & MCP-1), but higher HDL-c/LDL-c ratio. Characterization of gut microbiota indicated that PCA decreased the Firmicutes/Bacteroidetes ratio mainly by reducing the relative abundance of genus Enterococcus , which was positively correlated with the levels of LDL-c, AST, ALT and most of the up-regulated hepatic lipids by lipidomics analysis. FMT experiments showed that Enterococcus faecalis caused hepatic inflammation, fat deposition and insulin resistance with decreased expression of carnitine palmitoyltransferase-1 alpha ( CPT1α ), which can be reversed by PCA through inhibiting Enterococcus faecalis . Transcriptomics analysis suggested that Enterococcus faecalis caused a significant decrease in the expression of fibroblast growth factor 1 ( Fgf1 ), and PCA recovered the expression of Fgf1 with insulin-like growth factor binding protein 2 ( Igfbp2 ), insulin receptor substrate 1 ( Irs1 ) and insulin receptor substrate 2 ( Irs2 ). These results demonstrated that high proportion of gut Enterococcus faecalis accelerates MAFLD with decreased expression of CPT1α and Fgf1 , which can be prevented by dietary supplementation of PCA.

High-protein high-konjac glucomannan diets changed glucose and lipid metabolism by modulating colonic microflora and bile acid profiles in healthy mouse models

“…13,30,31 The high fiber diets potentially reduced the blood glucose levels through remodeling the gut microbes in the current study, and might act on glucose and lipid metabolism. 32–34 Therefore, in this study, high dietary fiber contents improved the glucose response in the healthy mouse models, although the body weight and feed intake of mice was not significantly altered. However, the limitation was that we did not detect changes to the insulin levels therefore we cannot directly declare that the insulin activity was changed by high fiber diets in this study.…”

Indole-3-acetamide from gut microbiota activated hepatic AhR and mediated the remission effect of Lactiplantibacillus plantarum P101 on alcoholic liver injury in mice

“…3G) suggested a potential alteration in the ratio of Firmicutes/Bacteroidota induced by alcohol consumption, which was effectively counteracted by L. plantarum P101 intervention. In a study conducted by Tan et al , 32 mice afflicted with metabolic associated fatty liver disease exhibited an elevated Firmicutes/Bacteroidota ratio. Notably, the ratio was effectively restored to the levels similar to that of the control group through protocatechuic acid treatment.…”

Preventive effect of low-carbohydrate high-fat dietary pattern on liver disease caused by alcohol consumption via a 6pgd-involved mechanism in mice

“…Emerging evidence suggests that gut microbes play a critical role in the occurrence and development of metabolic liver disease. 43,44 It has been reported that chronic alcohol intake impairs intestinal microbiota homeostasis and biological barrier, which contribute to the pathological process of ALD through the gut-liver interaction system. 45 Dietary patterns are closely related to gut microbiota homeostasis.…”