Agaricus bisporus Extract Exerts an Anti-Obesity Effect in High-Fat Diet-Induced Obese C57BL/6N Mice by Inhibiting Pancreatic Lipase-Mediated Fat Absorption

Abstract

Agaricus bisporus is well known as a source of polysaccharides that could improve human health. The objective of this study was to explore the anti-obesity effect of A. bisporus extract (ABE), abundant in polysaccharides, and its underlying mechanism. Pancreatic lipase inhibitory activity in vitro was determined after treatment with ABE and chitosan. Treatment with ABE and chitosan significantly decreased pancreatic lipase activity. Five-week-old male SD rats were randomly divided into three groups for acute feeding with vehicle, ABE at 80 mg/kg body weight (BW)/day, and ABE at 160 mg/kg BW/day. ABE dose-dependently increased plasma lipid clearance in an oral lipid tolerance test. Five-week-old male C57BL/6N mice were fed a control diet (CD), a high-fat diet (HFD), an HFD with ABE at 80 mg/kg BW/day, ABE at 160 mg/kg BW/day, or chitosan at 160 mg/kg BW/day for eight weeks. HFD-fed mice showed significant increases in body weight, fat mass, white adipose tissue, average lipid droplet size, and serum levels of glucose, triglyceride, ALT, and AST compared to those in the CD group. However, ABE or chitosan administration ameliorated these increases. ABE or chitosan significantly reduced dietary efficiency and increased fecal excretion levels of lipids, triglycerides, and total cholesterol. These in vitro and in vivo findings suggest that ABE might act as an anti-obesity agent by inhibiting pancreatic lipase-mediated lipid absorption, at least in part.

Keywords: Agaricus bisporus; chitosan; lipid absorption; obesity; pancreatic lipase; polysaccharide.

Figure 1

Quantitative confirmation of chitosan in ABE. Spectrophotometric profiles of D-glucosamine hydrolysate (Standard, 378.23 µg/mL) and ABE (Sample ID 1~3: 384, 450, and 424 µg/mL, respectively).

Figure 2

Effect of ABE administration on serum triglyceride and total cholesterol concentrations after oral administration of lipid emulsion in SD rats. SD rats were orally administered with ABE After 10 min, rats were given lipid emulsion at a dose of 10 mL/kg BW by oral gavage. Blood was collected at 0, 1, 2, 4, and 6 h after lipid emulsion administration and serum was obtained from blood. Triglyceride (A) and total cholesterol (C) concentrations in serum were measured using relevant assay kits. AUCs for serum triglyceride (B) and total cholesterol (D) were calculated. Each bar represents the mean ± SEM (n = 10). Different letters indicate significant differences between LC, L + A80, and L + A160 groups at p < 0.05.

Figure 3

Effects of ABE administration on adipose tissue weight and morphological changes in epididymal adipose tissues of HFD-fed HFD C57BL/6N mice. Mice fed HFD were treated with ABE using an oral gavage for eight weeks. (A) Adipose tissue weights in epididymal, retroperitoneal, mesenteric, and inguinal fat. Total white adipose tissue (WAT) weights calculated as the sum of epididymal, retroperitoneal, mesenteric, and inguinal fat. (B) Extracted epididymal adipose tissues were fixed, embedded in paraffin, and cut into 5 μm thick slices. Tissue sections were stained with H&E. Representative H&E-stained images of epididymal adipose tissue (n = 5, 200× magnification) are shown. Scale bar, 50 μm. (C) The size of the adipocytes was quantified by measuring the longest diameter of adipocytes. Each bar represents the mean ± SEM (n = 10). *** p < 0.001 significantly different from the CD group. Different letters indicate significant differences between HFD, HFD + A80, HFD + A160, and HFD + C160 groups at p < 0.05.

Figure 4

Effect of ABE administration on fat accumulation in livers of HFD-fed HFD C57BL/6N mice. Mice fed HFD were treated with ABE using an oral gavage for eight weeks. (A) Extracted liver tissues were fixed, embedded in paraffin, and cut into 5 μm thick slices. Tissue sections were stained with H&E. Representative H&E-stained images of liver tissue (n = 5, 200× magnification) are shown. (B) Liver tissues were embedded in Tissue-Tek OCT compound, serially sectioned to a thickness of 5 μm, and stained with oil-red O. Representative oil-red O-stained images of liver tissue (n = 5, 200× magnification) are shown. Scale bar: 50 μm. (C) Quantitative analysis of oil-red O-stained images of liver tissue. *** p < 0.001 significantly different from the CD group. Means without a common letter differ among the HFD, HFD + A80, HFD + A160, HFD + C160 group at p < 0.05.