In the modern society, the unhealthy lifestyle, such as excess calorie intake and lessened physical exercise contribute to the occurrence of metabolic diseases. As a kind of metabolism disorder disease, hyperlipidemia is characterized by abnormally increased lipid or lipoprotein levels in the blood which is generally accompanied by the elevation of total cholesterol (TG), triglyceride (TC) and low-density lipoprotein cholesterol (LDL-C), and the reduction of high-density lipoprotein cholesterol (HDL-C) (Nie et al., 2017). Hyperlipidemia is commonly regarded as the critical cause of cardiovascular disease (CVD), such as atherosclerosis, coronary artery disease, ischemic heart disease, myocardial infarction and stroke (Fukami et al., 2021). Moreover, dyslipidemia is also closely associated with obesity, type 2 diabetes mellitus (T2DM), nonalcoholic fatty liver disease (NAFLD) and cancers (Cobbina and Akhlaghi, 2017; Koene et al., 2016). Great developments of drugs in the therapy of hyperlipidemia have emerged during the past decades. Nevertheless, the medicine interventions such as statins (inhibitors of HMG-CoA) and fibrates (agonists of peroxisome proliferator-activated receptor) have complicated with adverse complications clinically, so the therapeutic effects of currently anti-hyperlipidemia drugs have been highly limited (Cham et al., 2016; Ferreira and da Silva, 2017; Ren et al., 2021; Yan et al., 2014). Therefore, it is urgent to explore new therapeutic drugs to meet the high prevalence of hyperlipidemia.

It has been significantly indicated that the natural products showed prominent potential in the improvements of metabolic syndromes (Wang et al., 2022, Wang et al., 2022, Wang et al., 2022). For example, curcumin has been recognized as potential candidate on reducing lipid levels effectively against hyperlipidemia (Maithilikarpagaselvi et al., 2016). Plantago asiatica L. polysaccharides have shown powerful effects on reversing lipid profiles, serum insulin and blood glucose, and enhancing the antioxidant capacity to attenuate hyperlipidemia in type 2 diabetes (Nie et al., 2019). At present, it seems a potential choice on developing multifunctional foods from natural sources as alternative therapeutic agents because of its diverse health benefits and low levels of adverse side effects (Li et al., 2019).

In the Asian countries, traditional Chinese Medicine has a long history which can go back to several thousands of years ago, and medicinal mushrooms are one of the traditional remedies commonly, such as Ganoderma lucidum (Chang et al., 2015). As a traditional medicinal mushroom known as the “plant of immortality”, G. lucidum has been widely used as a folk medicine in traditional Chinese medicine to improve health and longevity, and treat various human diseases, including dyslipidemia (de Camargo et al., 2022; Lee et al., 2020; Wu, 2018). In the recent years, the lipid-lowering, anti-lipidperoxidant and anti-obesity activities of G. lucidum polysaccharides have attracted the academic attentions of researchers worldwide (Fu et al., 2019; Wu, 2018). Besides, modern pharmacological studies have also demonstrated that G. lucidum showed other various medicinal applications such as antitumor, antidiabetic, antihyperglycemic, antioxidant, anti-inflammatory, anti-aging, immunomodulatory and hepatoprotective activities (Jin et al., 2017; Zhong et al., 2018). Polysaccharides have been considered to be the main bioactive constituents in G. lucidum, and diversified polysaccharides have been isolated from the fruiting bodies, mycelia, spores and mushroom residues of G. lucidum (Fu et al., 2019). Sang et al. have reported that polysaccharide extracted from sporoderm-broken spores of G. lucidum exhibited biological effects by modulating gut microbiota, maintaining intestinal barrier functions, ameliorating endotoxemia, and downregulating the TLR4/Myd88/NF-κB signaling pathway in adipose tissue (Sang et al., 2021). Li et al. have investigated the protective effects of G. lucidum mycelia polysaccharides (GLPS3) on chronic pancreatitis, and the results showed that GLPS3 increased the antioxidant activity, decreased the IFN-γ and TNF-α expressions, and modulated the composition and diversity of intestinal microbiota (Li et al., 2016). However, the underlying mechanism of G. lucidum mycelium polysaccharides (GLP) in ameliorating hyperlipidemia and dyslipidemia-related disorders is not completely clear.

In the present study, we aimed to investigate the influence of GLP on hyperlipidemia by using the high-fat diet (HFD)-induced mice model. The findings were helpful for exploring the potential lipid-lowering mechanisms of GLP, and may provide the theoretical basis for the dietary interventions on the treatment of hyperlipidemia.