Chaihu Shugan powder restores fatty acid synthesis to alleviate insulin resistance in metabolic syndrome by regulating the LXRα/SREBP-1 signaling pathway

Sisi Lei; Weihang Peng; Lulu Wu; Liyuan Yu; Meida Wang; Qingmin Li; Yi Deng; Shuai Zhao; Peiying Huang; Bojun Chen

doi:10.3389/fphar.2024.1442279

Chaihu Shugan powder restores fatty acid synthesis to alleviate insulin resistance in metabolic syndrome by regulating the LXRα/SREBP-1 signaling pathway

Front Pharmacol. 2024 Nov 5:15:1442279. doi: 10.3389/fphar.2024.1442279. eCollection 2024.

Authors

Sisi Lei^#^{1

2}, Weihang Peng^#¹, Lulu Wu^#¹, Liyuan Yu¹, Meida Wang¹, Qingmin Li³, Yi Deng⁴, Shuai Zhao⁴, Peiying Huang⁴, Bojun Chen^{1

4

5}

Affiliations

¹ The Second Clinical Medical School of Guangzhou University of Chinese Medicine, Guangzhou, China.
² Department of Traditional Chinese Medicine, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.
³ Department of Traditional Chinese Medicine, First People's Hospital of Chenzhou, Chenzhou, China.
⁴ Emergency Department of Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China.
⁵ Guangdong Provincial Key Laboratory of Research on Emergency in Traditional Chinese Medicine, Clinical Research Team of Prevention and Treatment of Cardiac Emergencies with Traditional Chinese Medicine, Guangzhou, China.

^# Contributed equally.

Abstract

Background: Metabolic syndrome (MS) is a significant risk factor for cardiovascular and cerebrovascular diseases, primarily driven by insulin resistance (IR). Although the herbal compound Chaihu Shugan powder (CSP) has demonstrated the potential to improve IR in animal models of MS, its mechanism of action remains incompletely understood. Therefore, this study aimed to investigate the biological pathways through which CSP exerts its therapeutic effects on IR in MS using both in vitro and in vivo methods.

Methods: The primary metabolites of CSP aqueous extract and CSP-containing serum were measured by LC-MS/MS. A mouse model of MS-related IR was induced by a high-fat, high-fructose diet combined with chronic immobilization stress. The CSP's therapeutic potential was evaluated through glucose and insulin tolerance tests and hepatic insulin signaling molecules (p-IRS-1, IRS-1, p-Akt, and Akt). The expression of lipid metabolism-related factors (FFA, DAG, LXRα, SREBP-1, FASN, and ACC) in the liver was also measured. Hepatocyte IR was modeled using high-glucose and high-insulin conditions, and CSP impact was evaluated using 2-NBDG uptake and insulin signaling molecule expression. The specific mechanism of CSP was explored using the LXRα agonist T0901317.

Results: The MS-related IR model exhibited a decreased p-Akt/Akt ratio and increased fasting glucose, insulin, homeostatic model assessment of IR, and hepatic lipid metabolism factors. Treatment with CSP mitigated these effects. In the hepatocyte IR model, CSP-containing serum improved glucose uptake and modulated the expression of insulin signaling and lipid metabolism factors. Furthermore, T0901317 reversed the beneficial effects of CSP, indicating the role of LXRα in CSP's therapeutic action.

Conclusion: The CSP ameliorated IR in MS by restoring fatty acid metabolism through the regulation of the LXRα/SREBP-1 signaling pathway.

Keywords: Chaihu Shugan powder; LXRα/SREBP-1; fatty acid synthesis; insulin resistance; metabolic syndrome.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was financially supported by grants from the National Natural Science Foundation of China (No. 82074342).