introduction
Lipid: It is a kind of biomolecule that can be dissolved in non-polar solvents, including fats, sterols, fat-soluble vitamins (such as vitamin A, D, E, and K), monoglycerides, diglycerides, triglycerides, sphingolipids, phospholipids and so on. Its main biological functions include serving as a cell barrier, signal transduction, substance transport, energy storage, etc., and it plays a very important role in life activities.
Lipidomics: It studies the structure, function, and interactions of lipids, their interactions with other metabolites and proteins, as well as their impacts on the physiological and pathological states of the whole body system.
Widely targeted lipidomics: Combining the dual advantages of the “wide coverage” of non-targeted lipids and the “accuracy and stability” of targeted lipids, it can stably detect thousands of lipids at one time. It covers multiple types of lipids such as fatty acids (FA), phosphatidylcholines (PC), phosphatidylethanolamines (PE), phosphatidylserines (PS), phosphatidic acids (PA), phosphatidylinositols (PI), phosphatidylglycerols (PG), lysophosphatidic acids (LPA), lysophosphatidylcholines (LPC), lysophosphatidylethanolamines (LPE), lysophosphatidylglycerols (LPG), lysophosphatidylserines (LPS), cholesterol esters (CE), ceramides (Cer), hexosylceramides (HexCer), diacylglycerols (DG), triacylglycerols (TG), monoacylglycerols (MG), eicosanoids, and acylcarnitines.
advantages
✔ High throughput: It can detect thousands of lipids at one time.
✔ Wide coverage: It simultaneously covers multiple types of lipids such as FA (fatty acids), PC (phosphatidylcholines), PE (phosphatidylethanolamines), PS (phosphatidylserines), PA (phosphatidic acids), PI (phosphatidylinositols), PG (phosphatidylglycerols), LPA (lysophosphatidic acids), LPC (lysophosphatidylcholines), LPE (lysophosphatidylethanolamines), LPG (lysophosphatidylglycerols), LPS (lysophosphatidylserines), CE (cholesterol esters), Cer (ceramides), HexCer (hexosylceramides), DG (diacylglycerols), TG (triacylglycerols), MG (monoacylglycerols), eicosanoids, and acylcarnitines.
✔ Reproducibility: The results of multiple detections have better reproducibility, effectively increasing the success rate of later data verification.
✔ High sensitivity: The high-sensitivity mass spectrometer AB SCIEX 6500+ is used, with the lower limit of detection as low as the picogram level.
✔ High specificity: The MRM (Multiple Reaction Monitoring) mode is adopted for the specific targeted detection of thousands of lipids.
Research Cases
Title：Qige Decoction attenuated non-alcoholic fatty liver disease through regulating SIRT6-PPARα-mediated fatty acid oxidation
Journal：Phytomedicine（双一区，IF=6.7）
Publication Date：2025.3
DOI：10.1016/j.phymed.2025.156395
Background: Sirtuin 6 (SIRT6) is a potential therapeutic target for non-alcoholic fatty liver disease (NAFLD) and has been demonstrated to regulate fatty acid oxidation (FAO) through its interaction with peroxisome proliferator-activated receptor α (PPARα). However, the impact of the SIRT6-PPARα pathway on the NAFLD phenotype has not been reported yet. Qige Decoction (QG), a traditional Chinese medicine (TCM) formula, is widely used in the treatment of disorders in glucose and lipid metabolism. Our previous experiments showed that QG reduced hepatic steatosis and provided preliminary evidence that QG might promote FAO. Nevertheless, a thorough understanding of the molecular mechanism by which QG regulates FAO requires further investigation.
Objective: To explore the role of the SIRT6-PPARα signaling pathway in the NAFLD phenotype, and to investigate the mechanism by which QG improves NAFLD and its relationship with FAO regulated by the SIRT6-PPARα signaling pathway.
Methods: In vivo studies divided high-fat diet (HFD)-induced NAFLD mice into two parts. The first part involved four groups: the control group (CON), the model group (MOD), the PPARα agonist (WY-14,643, WY) group, and the SIRT6 inhibitor (OSS-128,167, OS) group. The second part involved the CON group, the MOD group, the positive drug (POS) group, the low-dose QG (QGL) group, and the high-dose QG (QGH) group. Widely targeted lipidomics analysis was performed by UHPLC-QTOF/MS to analyze the differential lipids (DEL) in the liver, and transcriptome analysis was carried out on the Illumina sequencing platform to analyze the differentially expressed genes (DEGs). In vitro studies, co-immunoprecipitation and dual-luciferase assays were employed to further determine the molecular mechanism of the SIRT6-PPARα interaction. Lentiviral vectors, TG assays, and acetyl-CoA assays were used to clarify the indispensable role of the SIRT6-PPARα signaling pathway in QG-improved lipid accumulation in vitro.
Results: Downregulation of SIRT6 inhibited PPARα-mediated FAO and aggravated lipid accumulation in hepatocytes both in vivo and in vitro. SIRT6 bound to PPARα in HepG2 cells; however, SIRT6 activation of the PPARα promoter was not detected. As QG reduced lipid accumulation in hepatocytes, the SIRT6-PPARα signaling pathway was upregulated both in vivo and in vitro. However, the alleviating effect of QG on lipid accumulation was blocked by silencing SIRT6 in vitro.
Conclusion: This study confirmed that the inhibition of the SIRT6-PPARα signaling pathway aggravated dyslipidemia and hepatic steatosis in NAFLD. Moreover, this study provided the first in-depth analysis of the molecular mechanism by which QG improves NAFLD, involving the promotion of FAO through activating the SIRT6-PPARα signaling pathway. This study offers important insights for the clinical application of QG.