Anti-Obesity Activity of Sanghuangporus vaninii by Inhibiting Inflammation in Mice Fed a High-Fat Diet

Abstract

Obesity is an unhealthy condition associated with various diseases characterized by excess fat accumulation. However, in China, the prevalence of obesity is 14.1%, and it remains challenging to achieve weight loss or resolve this issue through clinical interventions. Sanghuangpours vaninii (SPV) is a nutritional fungus with multiple pharmacological activities and serves as an ideal dietary intervention for combating obesity. In this study, a long-term high-fat diet (HFD) was administered to induce obesity in mice. Different doses of SPV and the positive drug simvastatin (SV) were administered to mice to explore their potential anti-obesity effects. SPV regulated weight, serum lipids, and adipocyte size while inhibiting inflammation and hepatic steatosis. Compared with the vehicle-treated HFD-fed mice, the lowest decreases in total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) were 9.72%, 9.29%, and 12.29%, respectively, and the lowest increase in high-density lipoprotein cholesterol (HDL-C) was 5.88% after treatment with different doses of SPV. With SPV treatment, the analysis of gut microbiota and serum lipids revealed a significant association between lipids and inflammation-related factors, specifically sphingomyelin. Moreover, Western blotting results showed that SPV regulated the toll-like receptor (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway in HFD-diet mice, which is related to inflammation and lipid metabolism. This research presents empirical proof of the impact of SPV therapy on obesity conditions.

Keywords: Sanghuangpours vaninii; TLR4/NF-κB; inflammation; lipids; obesity.

Figure 1

SPV alleviated HFD-induced obesity and hyperlipidemia. (A) Establishment of animal models and agent administration management. (B) SPV suppressed body weight gain in HFD-fed mice (n = 6). SPV administration led to a rise in the serum level of (C) HDL-C and a reduction in the serum levels of lipid markers (D) LDL-C, (E) TC, and (F) TG in the HFD-fed mice (n = 6). (G) H&E staining of iWAT, eWAT, and pWAT (200×, scale bar: 100 μm). The data are presented as the mean ± SD. ^# p < 0.05, ^### p < 0.001 versus the vehicle-treated NCD-fed mice; * p < 0.05, ** p < 0.01, *** p < 0.001 versus the vehicle-treated HFD-fed mice.

Figure 2

SPV alleviated hepatic steatosis and inflammation. (A) The liver was examined through histopathological methods using Oil Red O staining (200×; scale bar: 100 µm) and H&E staining (200×; scale bar: 100 µm). In the HFD-fed mice, SPV suppressed the liver levels of (B) ALT, (C) AST, (D) TNF-α, (E) IL-1β, (F) IL-18, (G) IL-6, and (H) MCP-1, and suppressed the serum levels of (I) LEP and (J) INS. The data are shown as the mean ± SD (n = 6). ^## p < 0.01, ^### p < 0.001 versus the vehicle-treated NCD-fed mice; * p < 0.05, ** p < 0.01, *** p < 0.001 versus the vehicle-treated HFD-fed mice.

Figure 3

SPV regulated the gut microflora. (A) Venn diagram. (B) PCoA analysis. (C) Heatmap of the top 20 genera based on the average abundance values. (D) Graphical representation of the predicted abundances of secondary functional pathways derived from the MetaCyc database.

Figure 4

SPV regulated lipid metabolites in HFD-fed mice. (A) Heatmap of 30 significantly altered metabolites. (B) The associated heatmap of associated lipids. (C) Boxplots of 6 significantly altered metabolites in SPV-treated HFD-fed mice (n = 3). SPV treatment led to a decrease in the levels of (D) Cer and (E) FFA within the livers of HFD-fed mice (n = 6). ^# p < 0.05, ^## p < 0.01, ^### p < 0.001 versus the vehicle-treated NCD-fed mice; * p < 0.05, ** p < 0.01, *** p < 0.001 versus the vehicle-treated HFD-fed mice.

Figure 5

SPV regulated the TLR4/NF-κB signaling pathway in the livers of mice fed a high-fat diet. (A) SPV treatment resulted in reduced levels of TLR4, MyD88, and TRAF6 expression, and the phosphorylation levels of IKK α+β, IκBα, and NF-κB. (B) SPV treatment resulted in reduced expression level of PP2A and the phosphorylation level of PKC. (C) SPV treatment resulted in reduced expression levels of NLRP3, caspase 1, and IL-1β. Quantification data were normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or the corresponding total protein concentration and expressed as the percentage of the vehicle-treated NCD-fed mice. The data are shown as the mean ± SD (n = 3). ^## p < 0.01 and ^### p < 0.001 versus the vehicle-treated NCD-fed mice; * p < 0.05, ** p < 0.01, *** p < 0.001 versus the vehicle-treated HFD-fed mice.