Integration of Lipidomics and Transcriptomics Reveals the Efficacy and Mechanism of Qige Decoction on NAFLD

Simin Fan; Zunming Zhou; Jintong Ye; Yanfang Li; Keer Huang; Xuehong Ke

doi:10.1155/2022/9739032

Integration of Lipidomics and Transcriptomics Reveals the Efficacy and Mechanism of Qige Decoction on NAFLD

Evid Based Complement Alternat Med. 2022 Nov 21:2022:9739032. doi: 10.1155/2022/9739032. eCollection 2022.

Authors

Simin Fan^{1

2}, Zunming Zhou^{3

4}, Jintong Ye^{1

2}, Yanfang Li^{1

2}, Keer Huang³, Xuehong Ke³

Affiliations

¹ First Clinical School of Guangzhou University of Chinese Medicine, Guangzhou 510410, Guangdong, China.
² Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510410, Guangdong, China.
³ The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong, China.
⁴ Postdoctoral Research Station of Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong, China.

Abstract

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing as obesity and diabetes become more common. There are no drugs approved for NAFLD yet. Qige decoction (QGD), a traditional Chinese medicine (TCM) formula, is used for NAFLD and hyperlipidemia treatment in TCM and has shown hypolipidemic and hepatoprotective effects. This study tried to interpret the pharmacology and molecular mechanisms of QGD in NAFLD rats. Firstly, the therapeutic effects of QGD on high-fat diet (HFD)-induced NAFLD rats were evaluated. Then, integration of lipidomics and transcriptomics was conducted to explore the possible pathways and targets of QGD against NAFLD. QGD at low dosage (QGL) administration reduced serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) (P < 0.05). Liver histopathology indicated that QGL could alleviate hepatic steatosis. The main differential lipids (DELs) affected by QGD were glycerolipids. KEGG enrichment analysis suggested that the main pathways by which QGD improved NAFLD may be cholesterol metabolism, glycerolipid metabolism, and insulin resistance. Transcriptome sequencing identified 179 upregulated and 194 downregulated mRNAs after QGD treatment. An interaction network based on DELs and differential genes (DEGs) suggested that QGD inhibited hepatic steatosis mainly by reducing hepatic insulin resistance and triglyceride biosynthesis via the PPP1R3C/SIK1/CRTC2 and PPP1R3C/SIK1/SREBP1 signal axis, respectively. These findings indicated that QGD could protect against NAFLD induced by HFD. The improvement of hepatic insulin resistance and the reduction of triglyceride biosynthesis might be the potential mechanisms.