Gallic Acid Ameliorated Impaired Glucose and Lipid Homeostasis in High Fat Diet-Induced NAFLD Mice

Abstract

Gallic acid (GA), a naturally abundant plant phenolic compound in vegetables and fruits, has been shown to have potent anti-oxidative and anti-obesity activity. However, the effects of GA on nonalcoholic fatty liver disease (NAFLD) are poorly understood. In this study, we investigated the beneficial effects of GA administration on nutritional hepatosteatosis model by a more “holistic view” approach, namely 1H NMR-based metabolomics, in order to prove efficacy and to obtain information that might lead to a better understanding of the mode of action of GA. Male C57BL/6 mice were placed for 16 weeks on either a normal chow diet, a high fat diet (HFD, 60%), or a high fat diet supplemented with GA (50 and 100 mg/kg/day, orally). Liver histopathology and serum biochemical examinations indicated that the daily administration of GA protects against hepatic steatosis, obesity, hypercholesterolemia, and insulin resistance among the HFD-induced NAFLD mice. In addition, partial least squares discriminant analysis scores plots demonstrated that the cluster of HFD fed mice is clearly separated from the normal group mice plots, indicating that the metabolic characteristics of these two groups are distinctively different. Specifically, the GA-treated mice are located closer to the normal group of mice, indicating that the HFD-induced disturbances to the metabolic profile were partially reversed by GA treatment. Our results show that the hepatoprotective effect of GA occurs in part through a reversing of the HFD caused disturbances to a range of metabolic pathways, including lipid metabolism, glucose metabolism (glycolysis and gluconeogenesis), amino acids metabolism, choline metabolism and gut-microbiota-associated metabolism. Taken together, this study suggested that a 1H NMR-based metabolomics approach is a useful platform for natural product functional evaluation. The selected metabolites are potentially useful as preventive action biomarkers and could also be used to help our further understanding of the effect of GA in hepatosteatosis mice.

Metabolomics reveals the protective of Dihydromyricetin on glucose homeostasis by enhancing insulin sensitivity

“…Lactate, G-3-P, and F-6-P were correlated with glycolysis, suggesting modulation of the glycolytic pathway. A reduction in lactate levels was observed in the HFD group, which suggests a decreased rate of glycolysis and increased the expression of glycolysis-related enzymes in HFD-fed rats (Figs S3 and S11), consistent with a previous study47. Intriguingly, DMY treatment reversed these pathological changes (i.e., the reduction in the expression of G6Pase and PEPCK and the increase in the level of lactate).…”

Protective effect of quercetin on high-fat diet-induced non-alcoholic fatty liver disease in mice is mediated by modulating intestinal microbiota imbalance and related gut-liver axis activation

“…As previously described [23], in our in vivo model of NAFLD high fat diet feeding induced body weight gain, increased epididymal fat accumulation and developed hallmark characteristic of metabolic syndrome as elevated fasting blood glucose and insulin, and HOMA-IR (+52%, +328%, +537%, respectively, vs Control) ( Table 3).…”

Fermented Rhus verniciflua Stokes Extract Exerts an Antihepatic Lipogenic Effect in Oleic-Acid-Induced HepG2 Cells via Upregulation of AMP-Activated Protein Kinase

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