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Effect of Trilobatin from Lithocarpus polystachyus Rehd on Gut Microbiota of Obese Rats Induced by a High-Fat Diet.

ABSTRACT: Trilobatin was identified as the primary bioactive component in the Lithocarpus polystachyus Rehd (LPR) leaves. This study explored the antiobesity effect of trilobatin from LPR leaves and its influence on gut microbiota in obese rats. Results showed that trilobatin could significantly reduce body and liver weight gain induced by a high-fat diet, and the accumulation of perirenal fat, epididymal fat, and brown fat of SD (Male Sprague-Dawley) obese rats in a dose-independent manner. Short-chain fatty acids (SCFAs) concentrations increased, especially the concentration of butyrate. Trilobatin supplementation could significantly increase the relative abundance of Lactobacillus, Prevotella, CF231, Bacteroides, and Oscillospira, and decrease greatly the abundance of Blautia, Allobaculum, Phascolarctobacterium, and Coprococcus, resulting in an increase of the ratio of Bacteroidetes to Firmicutes (except the genera of Lactobacillus and Oscillospira). The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway predicted by the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) indicated the different relative metabolic pathways after trilobatin supplementation. This study may reveal the contribution of gut microbiota to the antiobesity effect of trilobatin from LPR leaves and predict the potential regulatory mechanism for obesity induced by a high-fat diet.

SUBMITTER: Shen H

PROVIDER: S-EPMC8001797 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The purpose of this study was to investigate the effects of leaf extract from Lithocarpus polystachyus Rehd. on type II diabetes mellitus (T2DM) and the active ingredients of this effect. In addition, this study determined, for the first time, the underlying molecular and pharmacological mechanisms of the extracts on hyperglycemia using long-term double high diet-fed and streptozotocin (STZ) induced type II diabetic mice. In the present study, leaf extract, phloridzin and trilobatin were assessed in vivo (gavage) and in vitro (non-invasive micro-test technique, NMT) in experimental T2DM mice. The biochemical parameters were measured including blood glucose and blood lipid level, liver biochemical indexes, and hepatic glycogen. The relative expression of glycometabolism-related genes was detected. The effect of leaf extracts on physiological glucose flux in liver tissue from control and T2DM mice was also investigated. Body weight of experimental T2DM mice increased significantly after the first week, but stabilized over the subsequent three weeks; body weight of all other groups did not change during the four weeks' study. After four weeks, all treatment groups decreased blood glucose, and treatment with leaf extract had numerous positive effects: a) promoted in glucose uptake in liver, b) increased synthesis of liver glycogen, c) reduced oxidative stress, d) up-regulation of glucokinase (GK), glucose transporter 2 (GLUT2), insulin receptor (IR) and insulin receptor substrate (IRS) expression in liver, e) down-regulation of glucose-6-phosphatase (G-6-P) expression, and f) ameliorated blood lipid levels. Both treatment with trilobatin or phloridzin accelerated liver glycogen synthesis, decreased oxidative stress and increased expression of GK. IRS and phosphoenolpyruvate carboxykinase (PEPCK) were both up-regulated after treatment with trilobatin. Expression of GLUT2, PEPCK and G-6-P were also increased in liver tissue after treatment with phloridzin. Our data indicate that leaf extract from L. polystachyus Rehd. has a preferable hypoglycemic effects than trilobatin or phloridzin alone. Leaf extract significantly increased glucose uptake and hepatic glycogen synthesis while also inducing a decline of hepatic gluconeogenesis and oxidative stress in T2DM mice. From this study, we draw conclusions that L. polystachyus promoted glycogen synthesis in T2DM mice, and that the active compounds were not only the trilobatin or phloridzin.

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Effect of Trilobatin from Lithocarpus polystachyus Rehd on Gut Microbiota of Obese Rats Induced by a High-Fat Diet.

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