Lipidomic analysis reveals therapeutic effects of Yijin-Tang on high-fat/high-cholesterol diet-induced obese mice

Abstract

Background: In Traditional Korean and Chinese medicine, the herbal remedy Yijin (Erchen)-Tang (YJT) is widely used to treat obesity-related disorders, and its therapeutic potential has been demonstrated in numerous studies. However, the systemic effect of YJT on obesity status and change of lipid metabolism by YJT still remains unknown. Purpose: This study aimed to investigate the therapeutic mechanism of the YJT on obesity by using lipidomics. Methods: To evaluate the effects of treatment with YJT on obesity, C57BL/6 J mice were fed a high-fat and high-cholesterol (HFHC, 40% fat and 1% cholesterol) diet for 8 weeks and treated them with YJT for an additional 6 weeks. We then performed untargeted lipidomic analysis using ultra-performance liquid chromatography/ quadrupole-time-of-flight mass spectrometry mass spectroscopy coupled with multivariate statistical analysis. Results: YJT ameliorated obesity induced systemic inflammation and improved insulin resistance. Additionally, YJT protected against HFHC-diet-induced hepatic inflammation. To explore specific changes in lipid metabolism associated with the therapeutic effects of YJT, we performed untargeted lipid profiling of the plasma. Partial least squares-discriminant analysis (PLS-DA) score plots showed that YJT altered the lipid metabolic pattern of HFHC mice. In particular, ceramides and triglycerides with saturated fatty acids and monounsaturated fatty acids were significantly changed by YJT, which were significantly associated with insulin resistance, the AGERAGE signaling pathway in diabetic complications and adipocytokine signaling pathway in pathway enrichment analysis. Thus, we analyzed the changes in adipocytes and adipokine caused by YJT, and confirmed that YJT alleviated adipocytes inflammation and macrophage infiltration, and reversed HFHC-induced alterations in leptin and adiponectin levels in adipose tissue and plasma. Conclusion: These data suggest that YJT ameliorates obesity-induced systemic inflammation and insulin resistance by regulating lipid metabolism, and demonstrated that lipidomic profiling is a useful method to investigate the therapeutic effects of herbal decoctions in traditional Korean and Chinese medicine.