A multi-targeting strategy to ameliorate high-fat-diet- And fructose-induced (western diet-induced) non-alcoholic fatty liver disease (NAFLD) with supplementation of a mixture of legume ethanol extracts
Journal
Food and Function
Journal Volume
11
Journal Issue
9
Pages
7545-7560
Date Issued
2020
Author(s)
Abstract
NAFLD (non-alcoholic fatty liver disease) is a multifactorial liver disease related to multiple causes or unhealthy conditions, including obesity and chronic inflammation. The accumulation of excess triglycerides, called steatosis, is known as a hallmark of an imbalance between the rates of hepatic fatty acid uptake/synthesis and oxidation/export. Furthermore, occurrence of NAFLD may lead to a cocktail of disease consequences caused by the altered metabolism of glucose, lipids, and lipoproteins, for instance, insulin resistance, type II diabetes, nonalcoholic steatohepatitis (NASH), liver fibrosis, and even hepatocarcinogenesis. Due to the complexity of the occurrence of NAFLD, a multi-targeting strategy is highly recommended to effectively address the issue and combat the causal loop. Ethanol extracts of legumes are popular supplements due to their richness and diversity in phytochemicals, especially isoflavones and anthocyanins. Although many of them have been reported to have efficacy in the treatment of different metabolic syndromes and obesity, there have not been many studies on them as a supplemental mixture. In this study, the alleviative effects of selected legume ethanol extracts (CrE) on high-fat-diet- and fructose-induced obesity, liver steatosis, and hyperglycemia are discussed. As revealed by the findings, CrE not only ameliorated obesity in terms of weight gained and enlargement of adipose tissue, but also significantly reduced the incidence of steatosis via phosphorylation of AMPK, resulting in inhibition of the downstream SREBP-1c/FAS pathway and an increase in an indicator of ?-oxidation (carnitine palmitoyl transferase 1a, CPT1A). Furthermore, CrE dramatically alleviated inflammatory responses, including both plasma and hepatic TNF-a, IL-6, and MCP-1 levels. CrE also had attenuating effects on hyperglycemia and insulin resistance and significantly reduced the fasting glucose level, fasting insulin level, and plasma leptin, and it exhibited positive effects in the Oral glucose tolerance test (OGTT) and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). At the molecular level, CrE could activate the PI3K/Akt/Glut2 pathway, which indicated an increase in insulin sensitivity and glucose uptake. Taken together, these results suggest that ethanol extracts of legumes could be potential supplements for metabolic syndromes, and their efficacy and effectiveness might facilitate the multi-targeting strategy required to mitigate NAFLD. ? 2020 The Royal Society of Chemistry.
SDGs
Other Subjects
Ethanol; Fatty acids; Flavonoids; Fructose; Glucose; Insulin; Lipids; Metabolism; Mixtures; Nutrition; Pathology; Chronic inflammation; Hepatocarcinogenesis; Inflammatory response; Insulin sensitivity; Metabolic syndromes; Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; Oral glucose tolerance tests; Diseases; fructose; interleukin 6; phosphatidylinositol 3 kinase; plant extract; sterol regulatory element binding protein 1; tumor necrosis factor; adverse event; animal; C57BL mouse; chemistry; dietary supplement; drug effect; Fabaceae; genetics; human; isolation and purification; lipid diet; liver; male; metabolism; nonalcoholic fatty liver; Western diet; Animals; Diet, High-Fat; Diet, Western; Dietary Supplements; Fabaceae; Fructose; Humans; Interleukin-6; Liver; Male; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Phosphatidylinositol 3-Kinases; Plant Extracts; Sterol Regulatory Element Binding Protein 1; Tumor Necrosis Factor-alpha
Type
journal article