Inonotus hispidus Protects against Hyperlipidemia by Inhibiting Oxidative Stress and Inflammation through Nrf2/NF-κB Signaling in High Fat Diet Fed Mice

Obesity is frequently associated with dysregulated lipid metabolism and lipotoxicity. Inonotus hispidus (Bull.: Fr.) P. Karst (IH) is an edible and medicinal parasitic mushroom. In this study, after a systematic analysis of its nutritional ingredients, the regulatory effects of IH on lipid metabolism were investigated in mice fed a high-fat diet (HFD). In HFD-fed mice, IH reversed the pathological state of the liver and the three types of fat and significantly decreased the levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG), and leptin (LEP) and increased the level of high-density liptein cholesterol (HDL-C) in serum. Meanwhile, IH ameliorated liver damage by reducing alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha (TNF-α), and plasminogen activator inhibitor-1 (PAI-1) levels in the liver and serum. Compared with HFD-fed mice, IH significantly modulated the gut microbiota, changed the relative abundances of microflora at different taxonomic levels, and regulated lipid levels. The results showed that 30 differential lipids were found. Results from Western blotting confirmed that IH regulated the nuclear factor erythroid-2 related factor 2 (Nrf2)/nuclear factor-kappa B (NF-κB) signaling pathway and oxidative stress. This study aimed to provide experimental evidence for the applicability of IH in obesity treatment.