Gypenosides ameliorate high-fat diet-induced nonalcoholic fatty liver disease in mice by regulating lipid metabolism

Tingting Zhou; Ligang Cao; Yimei Du; Lin Qin; Yanliu Lu; Qianru Zhang; Yuqi He; Daopeng Tan

doi:10.7717/peerj.15225

Gypenosides ameliorate high-fat diet-induced nonalcoholic fatty liver disease in mice by regulating lipid metabolism

PeerJ. 2023 Apr 11:11:e15225. doi: 10.7717/peerj.15225. eCollection 2023.

Authors

Tingting Zhou¹, Ligang Cao¹, Yimei Du¹, Lin Qin^{1

2}, Yanliu Lu^{1

2}, Qianru Zhang^{1

2}, Yuqi He^{1

2}, Daopeng Tan^{1

2}

Affiliations

¹ Guizhou Engineering Research Center of Industrial Key-technology for Dendrobium Nobile, Zunyi Medical University, Zunyi Medical University, Zunyi, Guizhou, China.
² Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi Medical University, Zunyi, Guizhou, China.

Abstract

Gypenosides (GP), extracted from the traditional Chinese herb Gynostemma pentaphyllum (Thunb.) Makino, have been used to treat metabolic disorders, including lipid metabolism disorders and diabetes. Although recent studies have confirmed their beneficial effects in nonalcoholic fatty liver disease (NAFLD), the underlying therapeutic mechanism remains unclear. In this study, we explored the protective mechanism of GP against NAFLD in mice and provided new insights into the prevention and treatment of NAFLD. Male C57BL6/J mice were divided into three experimental groups: normal diet, high-fat diet (HFD), and GP groups. The mice were fed an HFD for 16 weeks to establish an NAFLD model and then treated with GP for 22 weeks. The transcriptome and proteome of the mice livers were profiled using RNA sequencing and high-resolution mass spectrometry, respectively. The results showed that GP decreased serum lipid levels, liver index, and liver fat accumulation in mice. Principal component and heatmap analyses indicated that GP significantly modulated the changes in the expression of genes associated with HFD-induced NAFLD. The 164 differentially expressed genes recovered using GP were enriched in fatty acid and steroid metabolism pathways. Further results showed that GP reduced fatty acid synthesis by downregulating the expression of Srebf1, Fasn, Acss2, Acly, Acaca, Fads1, and Elovl6; modulated glycerolipid metabolism by inducing the expression of Mgll; promoted fatty acid transportation and degradation by inducing the expression of Slc27a1, Cpt1a, and Ehhadh; and reduced hepatic cholesterol synthesis by downregulating the expression of Tm7sf2, Ebp, Sc5d, Lss, Fdft1, Cyp51, Nsdhl, Pmvk, Mvd, Fdps, and Dhcr7. The proteomic data further indicated that GP decreased the protein expression levels of ACACA, ACLY, ACSS2, TM7SF2, EBP, FDFT1, NSDHL, PMVK, MVD, FDPS, and DHCR7 and increased those of MGLL, SLC27A1, and EHHADH. In conclusion, GP can regulate the key genes involved in hepatic lipid metabolism in NAFLD mice, providing initial evidence for the mechanisms underlying the therapeutic effect of GP in NAFLD.

Keywords: Data mining; Gypenosides; High-fat diet; NAFLD; Transcriptome.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3-Hydroxysteroid Dehydrogenases / metabolism
Animals
Diet, High-Fat / adverse effects
Fatty Acids / therapeutic use
Gynostemma / metabolism
Lipid Metabolism
Male
Mice
Non-alcoholic Fatty Liver Disease* / drug therapy
Proteomics

Substances

gypenoside
Fatty Acids
Nsdhl protein, mouse
3-Hydroxysteroid Dehydrogenases

Grants and funding

The study was supported by the National Nature Science Foundation of China (82260843, 82060649), the Department of Science and Technology of Guizhou Province (nos. QKHZC [2019]2953, QKHZC [2021]476, QKHPTRC [2017]5733-060, QKHTRC [2018]5772-001), and the Guizhou Engineering Research Center of Industrial Key-technology for Dendrobium Nobile (QJJ [2022]048). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.