摘要：SummaryGanoderma lucidumis a traditional Chinese medicine with a variety of active compounds and possesses adequate lipid-lowering and anti-atherosclerotic effects. However, its main active components and potential mechanisms still remain unclear. Here, we evaluated the anti-hyperlipidemic effect of the adenosine extract fromGanoderma lucidum(AEGL) in high-fat-diet (HFD)-induced hyperlipidemic ApoE−/−mice and explored the underlying biological mechanism by multi-omics analysis. Treatment with AEGL for 8 weeks significantly decreased the serum levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-c) by 45.59%, 41.22%, and 39.02%, respectively, as well as reduced liver TC and TG by 44.15% and 76.23%, compared with the HFD-only group. We also observed significant amelioration of hepatic steatosis without liver and kidney damage after AEGL treatment. Regulating the expression and acetylation/crotonylation of proteins involved in the PPAR signaling pathway may be one of the potential mechanisms involved in the observed lipid-lowering effects of AEGL.Graphical abstractDisplay OmittedHighlights•AEGL significantly reduced LDL, TC, and TG•AEGL improved hepatic steatosis without impairing liver and kidney function•AEGL regulated the expression and modification of proteins involved in the peroxisome proliferator-activated receptors (PPAR)Alternative medicine; Lipid; Physiology; Omics;
