Dietary Supplementation of Auricularia auricula-judae Polysaccharides Alleviate Nutritional Obesity in Mice via Regulating Inflammatory Response and Lipid Metabolism

Abstract

The incidence of lipid metabolism disorder and obesity that is caused by high-calorie diets is increasing year by year, which has become an urgent global health problem. This study was performed to explore the intervention effects of polysaccharides that were extracted from Auricularia auricula-judae resources in the Qinba Mountain area on nutritional obesity in C57BL/6J mice that was induced by high fat and high fructose diets (HFFD) and to investigate their underlying molecular mechanisms. The results showed that dietary supplementation of Auricularia auricula-judae polysaccharides (AAP) significantly improved mice's insulin resistance state, altered serum lipid metabolites, and slowed down body weight gain that was induced by HFFD. In addition, AAP supplementation decreased inflammatory factor levels and alleviated liver histomorphology changes. Furthermore, AAP down-regulated liver adipogenic-related gene expressions, suppressed cholesterol synthesis-related gene levels, up-regulated fatty acid β-oxidation-related gene expressions, and promoted cholesterol efflux-related gene expressions, thus improving mice hepatic lipid metabolism homeostasis. Moreover, the intervention effects were closely related to mitochondrial function. These results provide a scientific basis for the further development and utilization of Auricularia auricula-judae resources in the Qinba Mountain area.

Keywords: Auricularia auricula-judae polysaccharide; high-calorie diet; inflammatory response; lipid metabolism; nutritional obesity.

Figure 1

The effects of Auricularia auricula-judae polysaccharides on HFFD induced mice body weight and fat accumulation. Seven-week-old male C57BL/6J mice were randomized into 6 groups (n = 10 per group): ND, ND + AAP, HFFD, and HFFD + AAP (Auricularia auricula-judae polysaccharide, 50, 100, 200 mg/kg/day, in feed) for 12 weeks. (A) Above: Timeline of C57BL/6J mice with AAP and/or HFFD treatment; Below: Body weight; (B) Above: Representative mouse pictures after 12 weeks feeding; Below: Body weight gain; (C) Weight of subcutaneous fat and epididymal fat. The data are presented as the mean ± SEM, * p < 0.05, ** p < 0.01, vs. ND group, # p < 0.05, ## p < 0.01 vs. HFFD group.

Figure 2

Effects of Auricularia auricula-judae polysaccharides on food intake and food efficiency ratio of mice. During the 12 weeks of mice rearing, the (A) food intake and (B) fluid intake of the mice were recorded every week. The calculated (C) energy intake and (D) food efficiency ratio of the mice. The data are presented as the mean ± SEM, * p < 0.05, ** p < 0.01, vs. ND group, ## p < 0.01 vs. HFFD group.

Figure 3

Effects of Auricularia auricula-judae polysaccharides on glucose tolerance and insulin resistance in obese mice that was induced by HFFD. At the end of 12-week feeding, mice were detected by (A) glucose tolerance tests; (B) fasting glucose levels; (C) fasting insulin levels; (D) insulin resistance index, HOMA-IR. The data are presented as the mean ± SEM, n ≥ 6, * p < 0.05, ** p < 0.01, vs. ND group, # p < 0.05, ## p < 0.01 vs. HFFD group.

Figure 4

Effects of Auricularia auricula-judae polysaccharides on serum lipid levels in the HFFD-induced obese mice. (A) Triglyceride levels; (B) total cholesterol levels; (C) high-density lipoprotein cholesterol levels; (D) low-density lipoprotein cholesterol levels. The data are presented as the mean ± SEM, n ≥ 6, * p < 0.05, ** p < 0.01, vs. ND group, # p < 0.05, ## p < 0.01 vs. HFFD group.

Figure 5

Effects of Auricularia auricula-judae polysaccharides on lipids and lipid-related metabolites in obese mouse serum. (A) Positive ion mode; (B) Negative ion mode. n = 6.

Figure 6

Effects of Auricularia auricula-judae polysaccharides on liver histomorphology changes in obese mice that were fed by HFFD. (A) liver weight; (B) liver index; (C) representative HE staining of liver (×400). The data are presented as the mean ± SEM, n ≥ 6, ** p < 0.01, vs. ND group, ## p < 0.01 vs. HFFD group.

Figure 7

Effects of Auricularia auricula-judae polysaccharides on liver inflammatory response in HFFD-induced obese mice. The mRNA levels of inflammatory response including (A) IL-1β, (B) IL-6, (C) IL-10, (D) TNF-α. The data are presented as the mean ± SEM, n ≥ 6, * p < 0.05, ** p < 0.01, vs. ND group, # p < 0.05, ## p < 0.01 vs. HFFD group.

Figure 8

The effects of Auricularia auricula-judae polysaccharides on liver lipid metabolism-related gene expressions in obese mice that were induced by HFFD. (A) mRNA levels of lipogenic genes including Pparg, Srebp1c, Fasn, Acaca, and ME1; (B) The mRNA levels of cholesterol synthesis genes including Hmgcr, Acat2, LXRβ, Abcg5, and Abcg8; (C) mRNA levels of lipolytic genes and mitochondrial-related genes including Cpt1a, Cpt2, Pgc1α, Sirt1, Tfam, and COXII. The data are presented as the mean ± SEM, n ≥ 6, * p < 0.05, ** p < 0.01, vs. ND group, # p < 0.05, ## p < 0.01 vs. HFFD group.