Tocopheryl quinone improves non-alcoholic steatohepatitis (NASH) associated dysmetabolism of glucose and lipids by upregulating the expression of glucagon-like peptide 1 (GLP-1) via restoring the balance of intestinal flora in rats

Abstract

Context

Glucagon-like peptide 1 (GLP-1) and α-tocopheryl quinone can promote the growth of intestinal flora and affect the pathogenesis of non-alcoholic steatohepatitis (NASH).

Objective

This study determines the molecular mechanism of the effect of tocopheryl quinone in the treatment of high cholesterol and cholate diet (HFCC)-induced NASH.

Materials and methods

Thirty-two male Sprague Dawley (SD) rats grouped as lean control (LC), LC + tocopheryl quinone (1 mL of 3 × 10⁶ dpm tocopheryl quinone via i.p. injection), HFCC (5.1 kcal/g of fat diet), and HFCC + tocopheryl quinone. Profiles of intestinal flora were assessed by 16S ribosomal ribonucleic acid–based analysis. Levels and activity of GLP-1, interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α) in intestinal tissues were detected by immunohistochemistry (IHC), Western blot and enzyme-linked immunosorbent assay (ELISA).

Results

HFCC rats presented higher levels of cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL), while tocopheryl quinone reversed the effects of HFCC. HFCC dysregulated malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), Vitamin E, 12-hydroxyeicosatetraenoic acid (12-HETE), 13-hydroxyoctadecadienoic acid (13-HODE) and nuclear factor kappa B (NF-κB), and the effects of HFCC were reversed by the treatment of tocopheryl quinone. Also, GLP-1 in the HFCC group was down-regulated while the IL-6 and TNF-α activity and endotoxins were all up-regulated. HFCC significantly decreased the number and diversity of bacteria, whereas tocopheryl quinone substantially restored the balance of intestinal flora and promoted the growth of both Bacteroides and Lactobacilli in vitro.

Discussion and conclusions

α-Tocopheryl quinone relieves HFCC-induced NASH via regulating oxidative stress, GLP-1 expression, intestinal flora imbalance, and the metabolism of glucose and lipids.

Keywords:

• Diabetes mellitus
• high cholesterol
• cholate diet

Author contributions

TS BZ and BDL performed the majority of the laboratory work, statistics and data analysis and participated in writing. QJR XMC and BDL were involved in writing. All authors conceived and designed the experiments and drafted the manuscript.

Disclosure statement

The authors report no declarations of interest. The authors alone are responsible for the content and writing of the article.

Data availability statement

The data sets generated during and/or analysed during this study are available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by the Zhejiang Traditional Chinese Medicine Science and Technology Project [2019ZQ029].