Application of isaria feline mycelium in preparation of product for improving glucose and lipid metabolism disorder induced by high fat diet

Abstract

The invention discloses an application of an Isaria felina mycelium in preparation of a product for improving glycolipid metabolism disorder induced by high fat diet. The Isaria felina strain is a strain with the preservation number of CGMCC NO.0706. The invention further discloses a preparation method of the Isaria felina mycelium. The isaria feline mycelium can be used for improving glucose tolerance and insulin sensitivity and inhibiting hyperglycemia induced by high fat diet; the dyslipidemia caused by high-fat diet is improved; fat accumulation induced by high fat diet is inhibited; preventing liver tissue damage induced by a high fat diet (HFD); liver lipid deposition and liver fatty degeneration induced by high fat diet are prevented, and the liver lipid metabolism function is improved.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of Isaria felina application, in particular to an application of Isaria felina mycelium in preparation of a product for treating glycolipid metabolism disorder. BACKGROUND

[0002] The World Obesity Federation (WOF) predicts that by 2035, more than 4 billion people worldwide will be obese or overweight, accounting for 51% of the global population. Obesity-induced glycolipid metabolism disorder is closely related to type 2 diabetes mellitus (T2DM), metabolic dysfunction-associated fatty liver disease (MASLD), cardiovascular disease (CVD), hypertension, hyperlipidemia, and inflammation. High-fat diet (HFD) is the main cause of obesity and glycolipid metabolism disorder in the body.

[0003] Isaria felina is a fungus obtained by culturing a strain isolated from natural Cordyceps sinensis fruiting bodies. It has been included and preserved by the China General Microbiological Culture Collection Center, with the preservation number CGMCC NO. 0706.

[0004] Isaria felina mycelium powder (IF) is rich in fungal polysaccharides and has been observed to have immune protection, kidney protection, and tumor inhibition. Chinese patent CN119548541A discloses the application of Isaria felina in the preparation of a drug for treating osteoporosis. Chinese patent CN118924799A discloses the use of Isaria felina mycelium in the preparation of a liver protection drug. Chinese patent CN114533681A discloses the application of Isaria felina mycelium in the preparation of a drug for treating type 2 diabetes. Chinese patent CN110664849A discloses the application of Isaria felina mycelium in the treatment of autoimmune thyroiditis. Chinese patent CN102813669A discloses the application of Isaria felina crude polysaccharide in the preparation of an anti-tumor drug.

[0005] However, the role and mechanism of Isaria felina in HFD-induced glycolipid metabolism disorder are not clear, and there is no relevant report. SUMMARY

[0006] The technical problem to be solved by the present application is to provide a new use of Isaria felina mycelium.

[0007] According to one aspect of the present application, there is provided an application of Isaria felina mycelium in the preparation of a product for improving HFD-induced glycolipid metabolism disorder.

[0008] The cat's claw species is a strain with a preservation number of CGMCC NO. 0706.

[0009] Further, the preparation method of the cat's claw mycelium comprises: The millet, sucrose, MgSO4, KH2PO4 and distilled water are used to prepare a solid culture medium. The solid culture medium is sterilized at 120-130 DEG C, and after being cooled to room temperature, the cat's claw strain is inoculated. The inoculated culture bottle is placed in an environment with a temperature of 20-25 DEG C and a relative humidity of 40-60% for fermentation culture. When the mycelium grows to fill the entire culture bottle, the culture is collected and baked into a mycelium block in a drying oven.

[0010] Further, in the above solid culture medium, the millet, sucrose, MgSO4 and KH2PO4 are included in a mass fraction of 830-850 parts, 40-45 parts, 2.5-3.0 parts and 5.0-6.0 parts, respectively.

[0011] Further, the millet, sucrose, MgSO4 and KH2PO4 are included in a mass fraction of 840 parts, 42 parts, 2.8 parts and 5.5 parts, respectively.

[0012] Further, the product comprises at least one of a medicine, a health product and food.

[0013] Further, the cat's claw mycelium improves the glycolipid metabolism disorder induced by a high-fat diet (HFD) in at least one of the following ways: (1) improving glucose tolerance and insulin sensitivity, and inhibiting hyperglycemia induced by a high-fat diet (HFD); (2) improving blood lipid metabolism disorder induced by a high-fat diet (HFD); (3) inhibiting fat accumulation induced by a high-fat diet (HFD); (4) preventing liver tissue damage induced by a high-fat diet (HFD); (5) preventing liver lipid deposition and liver steatosis induced by a high-fat diet (HFD), and improving liver lipid metabolism function.

[0014] According to another aspect of the present application, a medicine for treating and preventing glycolipid metabolism disorder is provided, and the active ingredient comprises the cat's claw mycelium described above.

[0015] The experimental results show that: (1) IF can reduce the HFD-induced increase in body weight of mice, alleviate the obesity phenotype, and improve the HFD-induced polydipsia and polyphagia of mice in the later experimental period; IF can reduce the HFD-induced increase in serum Glu and fasting blood glucose levels of mice, improve glucose tolerance and insulin sensitivity, and inhibit the occurrence and development of hyperglycemia in HFD-induced mice; IF can reduce the HFD-induced increase in serum TC, TG, LDL-C and HDL-C levels of mice, and significantly improve the abnormal lipid metabolism in HFD-induced mice in the long term; IF can reduce the HFD-induced increase in fat tissue weight, fat index and fat cell volume of mice, and inhibit fat accumulation in HFD-induced mice.

[0016] (2) IF can alleviate the HFD-induced morphological changes in the liver of mice, the significant increase in vacuoles in the liver, and prevent the HFD-induced damage to the liver tissue of mice; IF can reduce the HFD-induced increase in TC and TG content in the liver of mice, the enlargement of lipid droplets in the liver, prevent the HFD-induced lipid deposition and fatty degeneration in the liver of mice, and improve the lipid metabolism function of the liver in HFD-induced mice; IF can reduce the HFD-induced increase in liver weight, liver index, and serum AST, ALT and ALP levels of mice, and maintain the healthy metabolic function of the liver in HFD-induced mice.

[0017] The present application clarifies the role and mechanism of C. catenulatum mycelium in HFD-induced glucose and lipid metabolism disorders, and can be used for preventing and treating HFD-induced glucose and lipid metabolism disorders. BRIEF DESCRIPTION OF DRAWINGS

[0018] Figure 1 Effects of IF on the body weight, diet and water consumption of HFD-induced mice are shown; Figure 2 Effects of IF on the blood glucose levels of HFD-induced mice are shown; Figure 3 Effects of IF on the serum TC, TG, LDL-C and HDL-C of HFD-induced mice are shown; Figure 4 Effects of IF on the fat tissue of HFD-induced mice are shown; Figure 5 Effects of IF on the liver morphology and tissue morphology of HFD-induced mice are shown; Figure 6 Effects of IF on the liver lipid and function of HFD-induced mice are shown. DETAILED DESCRIPTION

[0019] The C. catenulatum strain involved in the present embodiment has been deposited and preserved by the China General Microbiological Culture Collection Center, with the preservation number CGMCC NO. 0706.

[0020] Example 1 Preparation of Isaria felina mycelium powder Millet, sucrose, MgSO4, KH2PO4 and distilled water were used to prepare a solid culture medium. The solid culture medium was sealed in a culture bottle and sterilized at 125°C. After cooling to room temperature, Isaria felina spores were inoculated. The inoculated culture bottle was placed in an environment with a temperature of 22°C, a relative humidity of 50%, and good ventilation for fermentation and culture. After the mycelium grew throughout the culture bottle, the culture was collected and dried in a drying oven to form a mycelial block. The mycelial block was then ground into powder using a grinder, and the powder was sieved to obtain Isaria felina mycelium powder. In the above solid culture medium, the mass fractions of millet, sucrose, MgSO4, and KH2PO4 were 840, 42, 2.8, and 5.5 parts, respectively.

[0021] Example 2 Preparation of Isaria felina mycelium powder Millet, sucrose, MgSO4, KH2PO4 and distilled water were used to prepare a solid culture medium. The solid culture medium was sealed in a culture bottle and sterilized at 120°C. After cooling to room temperature, Isaria felina spores were inoculated. The inoculated culture bottle was placed in an environment with a temperature of 25°C, a relative humidity of 40%, and good ventilation for fermentation and culture. After the mycelium grew throughout the culture bottle, the culture was collected and dried in a drying oven to form a mycelial block. The mycelial block was then ground into powder using a grinder, and the powder was sieved to obtain Isaria felina mycelium powder. In the above solid culture medium, the mass fractions of millet, sucrose, MgSO4, and KH2PO4 were 830, 45, 2.5, and 6.0 parts, respectively.

[0022] Example 3 Preparation of Isaria felina mycelium powder Millet, sucrose, MgSO4, KH2PO4 and distilled water were used to prepare a solid culture medium. The solid culture medium was sealed in a culture bottle and sterilized at 130°C. After cooling to room temperature, Isaria felina spores were inoculated. The inoculated culture bottle was placed in an environment with a temperature of 20°C, a relative humidity of 60%, and good ventilation for fermentation and culture. After the mycelium grew throughout the culture bottle, the culture was collected and dried in a drying oven to form a mycelial block. The mycelial block was then ground into powder using a grinder, and the powder was sieved to obtain Isaria felina mycelium powder. In the above solid culture medium, the mass fractions of millet, sucrose, MgSO4, and KH2PO4 were 850, 40, 3.0, and 5.0 parts, respectively.

[0023] The following embodiments establish a high-fat diet (HFD)-induced obese mouse model, and give Isaria felina mycelium powder (IF) intervention, study the effect of IF on HFD-induced glucose and lipid metabolism disorder in mice, and comprehensively use metabolomics and metagenomics to determine the key role of bile acid spectrum and intestinal flora in IF regulating HFD-induced glucose and lipid metabolism disorder in mice.

[0024] SPF level Kunming mice (KM) selected in this embodiment were bred by the Experimental Animal Center of Shanxi Tumor Hospital, and the experimental animal production license number was SCXK (Jin) 2022-0002. The mycelium of Isaria felina obtained in Example 1 was used for experiments.

[0025] 1. Effect of IF on body weight, diet and water of mice induced by HFD The representative body types of mice in each group are shown in Figure 1 (A). As can be seen from the figure, the body size of mice in the Model group was larger than that in the other groups, the body size of mice in the WKB, IF50 and IF100 groups was similar, and the body size of mice in the IF200 group was smaller than that in the WKB, IF50 and IF100 groups and similar to that in the Control group.

[0026] The body weight changes of mice in each group are shown in Figure 1 (B). The body weight gain changes of mice in each group are shown in Figure 1 (C). As can be seen from Figure 1 (B-C), before HFD feeding, the body weights of mice in each group were basically the same. During the process of continuous 12-week HFD feeding, the body weight of mice in the Model group increased the fastest and was significantly higher than that in the Control group. The body weight gain of mice in the WKB, IF50, IF100 and IF200 groups was slowed down to varying degrees.

[0027] The body weight gain of mice in each group is shown in Figure 1 (D). As can be seen from the figure, compared with the Control group, the body weight of mice in the Model group increased, and the difference was statistically significant (P < 0.01). Compared with the increase of the Model group, the body weight of mice in the WKB, IF50, IF100 and IF200 groups was reduced by 5.29%, 4.61%, 4.69% and 12.56%, respectively, and the difference of the IF200 group was statistically significant (P < 0.01).

[0028] The diet changes of mice in each group are shown in Figure 1 (E). As can be seen from the figure, the diet changes of each group decreased or increased basically consistently. During the experiment, the diet of the Control group was always more than that of the other groups. From the 8th week, the diet of mice in the Model group was more than that in the WKB, IF50, IF100 and IF200 groups.

[0029] The average diet of mice in each group is shown in Figure 1(F), as shown in the figure, compared with the Control group, the average food intake of the Model group mice decreased, the difference was statistically significant (P < 0.01), and the difference between the Model group and the WKB, IF50, IF100 and IF200 groups was not statistically significant (P > 0.05).

[0030] The water consumption of mice in each group is shown in Figure 1 (G), as shown in the figure, the water consumption of each group decreased or increased basically consistently. Before the 9th week, the water consumption of the Control group mice was more than that of the other groups. From the 9th week, the water consumption of the Model group mice was more than that of the remaining groups.

[0031] The average water consumption of mice in each group is shown in Figure 1 (H), as shown in the figure, compared with the Control group, the average water consumption of the Model group mice had no statistically significant difference (P > 0.05), and the average water consumption of the Model group and the WKB, IF50, IF100 and IF200 groups also had no statistically significant difference (P > 0.05).

[0032] The above research results show that HFD can induce mice to have weight gain and polydipsia and polyphagia, while WKB and IF can reduce the weight gain of HFD-induced mice and improve the polydipsia and polyphagia of HFD-induced mice in the later experimental period.

[0033] 2. Effect of IF on blood glucose level of mice induced by HFD The OGTT test results of mice in each group at the 6th week are shown in Figure 2 (A), as shown in the figure, before oral glucose, the FBG level of the Model group mice was the highest, and the FBG level of the Control group mice was the lowest. From 0-30 min after oral glucose, the blood glucose levels of mice in each group increased. Compared with the Control group, the blood glucose level of the Model group mice increased rapidly. Compared with the Model group, the blood glucose level of the WKB, IF50, IF100 and IF200 groups showed a slow rising trend, and the blood glucose level was lower than that of the Model group. From 30-120 min after oral glucose, the blood glucose levels of mice in each group decreased, and the blood glucose level of the Model group mice remained the highest. After 120 min of oral glucose, the blood glucose level of the Model group mice was still higher than that of the other groups.

[0034] The FBG content of mice in each group at the 6th week is shown in Figure 2 (B), as shown in the figure, compared with the Control group, the FBG content of the Model group mice increased, and the difference was statistically significant (P < 0.05). Compared with the Model group, the FBG content of the WKB, IF50, IF100 and IF200 groups decreased to varying degrees, and the IF50 group decreased the most.

[0035] The area under the curve (AUC) of OGTT test of each group of mice at 6 weeks is shown in Figure 2 (C), as can be seen from the figure, compared with the Control group, the Model group mice OGTT-AUC increased, the difference was statistically significant (P < 0.01), compared with the Model group, WKB, IF50, IF100 and IF200 group mice OGTT-AUC all have different degrees of reduction, and IF50 group difference was statistically significant (P <0.05).

[0036] The IPGTT test results of each group of mice at 12 weeks are shown in Figure 2 (D), as can be seen from the figure, before intraperitoneal injection of glucose, the Model group mice FBG level was the highest, and the Control group mice FBG level was the lowest; intraperitoneal injection of glucose 0-30 min, the blood glucose level of each group of mice increased, compared with the Control group, the blood glucose level of Model group mice increased rapidly, compared with the Model group, the blood glucose level of WKB, IF50, IF100 and IF200 group mice showed a slow rising trend, and the blood glucose level was lower than that of Model group, the rising curve of WKB group was most close to that of Control group; intraperitoneal injection of glucose 30-120 min, the blood glucose level of each group of mice decreased, the blood glucose level of Model group mice remained the highest, the blood glucose level change curve of WKB group mice was basically the same as that of Control group; intraperitoneal injection of glucose 120 min, the blood glucose level of Model group mice was still higher than that of other groups, and the blood glucose level of WKB and IF200 group mice was close to that of Control group.

[0037] The FBG content of each group of mice at 12 weeks is shown in Figure 2 (E), as can be seen from the figure, compared with the Control group, the Model group mice FBG content increased, the difference was statistically significant (P < 0.01), compared with the Model group, WKB, IF50, IF100 and IF200 group mice FBG content all have different degrees of reduction, and WKB, IF50 group difference was statistically significant (P <0.01).

[0038] The area under the curve (AUC) of IPGTT test of each group of mice at 12 weeks is shown in Figure 2 (F), as can be seen from the figure, compared with the Control group, the Model group mice IPGTT-AUC increased, the difference was statistically significant (P < 0.01), compared with the Model group, WKB, IF50, IF100 and IF200 group mice IPGTT-AUC all have different degrees of reduction, the difference was statistically significant (P <0.05).

[0039] The IPITT test results of each group of mice at 12 weeks are shown inFigure 2 (G), it can be seen from the figure that before intraperitoneal injection of insulin, the blood glucose level of Model group mice was the highest, and the blood glucose level of Control group mice was the lowest; 0-30 min after intraperitoneal injection of insulin, the blood glucose level of each group of mice decreased, compared with Control group, the blood glucose level of Model group mice decreased slowly, compared with Model group, the blood glucose level of WKB, IF50, IF100 and IF200 group mice showed a rapid downward trend, and the blood glucose level was lower than that of Model group; 30-120 min after intraperitoneal injection of insulin, the blood glucose level of each group of mice increased, and the blood glucose level of Model group mice remained the highest; 120 min after intraperitoneal injection of insulin, the blood glucose level of Model group mice was still higher than that of other groups.

[0040] The area under the curve (AUC) of IPITT test of each group of mice at 12 weeks is shown in Figure 2 (H), it can be seen from the figure that compared with Control group, the IPITT-AUC of Model group mice increased, and the difference was statistically significant (P < 0.01), compared with Model group, the IPITT-AUC of WKB, IF50, IF100 and IF200 group mice all decreased to different degrees, and the difference was statistically significant (P < 0.05).

[0041] The serum Glu content of each group of mice at 12 weeks is shown in Figure 2 (I), it can be seen from the figure that compared with Control group, the serum Glu content of Model group mice increased, and the difference was statistically significant (P < 0.01), compared with Model group, the serum Glu content of WKB, IF50, IF100 and IF200 group mice all decreased to different degrees, and the difference was statistically significant (P < 0.05).

[0042] The above results show that long-term HFD can cause hyperglycemia, glucose intolerance and decreased insulin sensitivity in mice; WKB and IF can improve glucose intolerance and increase insulin sensitivity in mice, thereby inhibiting the occurrence and development of hyperglycemia in mice.

[0043] 3. Effect of IF on serum TC, TG, LDL-C and HDL-C of mice induced by HFD The serum TC content of each group of mice at 6 weeks and 12 weeks is shown in Figure 3(A), it can be seen from the figure that at the 6th week, compared with the Control group, the TC content in the serum of the Model group mice increased, and the difference was statistically significant (P < 0.01), compared with the Model group, the TC content in the serum of the WKB, IF50, IF100 and IF200 groups of mice decreased to different degrees, and the differences of the IF50, IF100 and IF200 groups were statistically significant (P < 0.05); at the 12th week, compared with the Control group, the TC content in the serum of the Model group mice increased, and the difference was statistically significant (P < 0.01), compared with the Model group, the TC content in the serum of the WKB group of mice increased, but the difference was not statistically significant (P > 0.05), the TC content in the serum of the IF50 and IF100 groups of mice decreased, and the differences were statistically significant (P < 0.05), and the TC content in the serum of the IF200 group of mice was basically the same as that of the Model group. Compared with the Control group, the increase of the serum TC of the Model group at the 12th week was 28.94% higher than that at the 6th week.

[0044] The TG content in the serum of each group of mice at the 6th week and the 12th week is shown in Table 2. Figure 3 (B), it can be seen from the figure that at the 6th week, compared with the Control group, the TG content in the serum of the Model group mice increased, and the difference was statistically significant (P < 0.01), compared with the Model group, the TG content in the serum of the WKB, IF50, IF100 and IF200 groups of mice decreased to different degrees, and the differences of the IF100 and IF200 groups were statistically significant (P < 0.01); at the 12th week, compared with the Control group, the TG content in the serum of the Model group mice increased, and the difference was statistically significant (P < 0.01), compared with the Model group, the TG content in the serum of the WKB group of mice increased, and the difference was not statistically significant (P > 0.05), the TG content in the serum of the IF50 and IF100 groups of mice decreased, and the differences were statistically significant (P < 0.05), and the TG content in the serum of the IF200 group of mice was basically the same as that of the Model group. Compared with the Control group, the increase of the serum TG of the Model group at the 12th week was 91.13% lower than that at the 6th week.

[0045] The LDL-C content in the serum of each group of mice at the 6th week and the 12th week is shown in Table 3. Figure 3(C), it can be seen from the figure that at the 6th week, compared with the Control group, the LDL-C content in the serum of the Model group mice increased, and the difference was statistically significant (P < 0.01), compared with the Model group, the LDL-C content in the serum of the WKB, IF50, IF100 and IF200 groups of mice decreased to different degrees, but the difference was not statistically significant (P > 0.05); at the 12th week, compared with the Control group, the LDL-C content in the serum of the Model group mice increased, and the difference was statistically significant (P < 0.01), compared with the Model group, the LDL-C content in the serum of the WKB group of mice increased, but the difference was not statistically significant (P > 0.05), the LDL-C content in the serum of the IF50 and IF100 groups of mice decreased, and the difference was statistically significant (P < 0.05), and the LDL-C content in the serum of the IF200 group of mice was higher than that of the Model group. Compared with the Control group, the increase of LDL-C in the serum of the Model group at the 12th week was 119.57% higher than that at the 6th week.

[0046] The HDL-C content in the serum of each group of mice at the 6th week and the 12th week is shown in Table 4. Figure 3 (D), it can be seen from the figure that at the 6th week, compared with the Control group, the HDL-C content in the serum of the Model group mice increased, and the difference was statistically significant (P < 0.01), compared with the Model group, the HDL-C content in the serum of the WKB, IF50, IF100 and IF200 groups of mice decreased to different degrees, and the difference between the IF100 and IF200 groups was statistically significant (P < 0.05); at the 12th week, compared with the Control group, the HDL-C content in the serum of the Model group mice increased, and the difference was statistically significant (P < 0.01), compared with the Model group, the HDL-C content in the serum of the WKB group of mice increased, but the difference was not statistically significant (P > 0.05), the HDL-C content in the serum of the IF50 and IF100 groups of mice decreased, and the difference was statistically significant (P < 0.05), and the HDL-C content in the serum of the IF200 group of mice was basically the same as that of the Model group. Compared with the Control group, the increase of HDL-C in the serum of the Model group at the 12th week was 20.22% higher than that at the 6th week.

[0047] The above results show that long-term HFD can cause abnormal blood lipid levels in mice; WKB has no significant effect on long-term improvement of HFD-induced abnormal serum lipid metabolism in mice, while IF can significantly improve long-term HFD-induced abnormal serum lipid metabolism in mice.

[0048] 4. Effect of IF on adipose tissue of mice induced by HFD The fat weight and fat index of each group of mice at the 6th week and the 12th week are shown in Table 6.Figure 4 (A) As shown in the figure, at week 6, compared with the control group, the model group mice had increased fat weight and adipose index, and the difference was statistically significant (P < 0.01). Compared with the model group, the WKB, IF50, IF100 and IF200 groups mice all had decreased fat weight and adipose index to varying degrees. At week 12, compared with the control group, the model group mice had increased fat weight and adipose index, and the difference was statistically significant (P < 0.01). Compared with the model group, the WKB, IF50, IF100 and IF200 groups mice all had decreased fat weight and adipose index to varying degrees, and the difference was statistically significant (P < 0.05).

[0049] H&E stained tissue sections of epididymal fat from mice in each group at weeks 6 and 12 are shown below. Figure 4 (B) As shown in the figure, the adipocytes of mice in the Control group were smaller and had a regular structure. The adipocytes of mice in the Model group were significantly larger than those in other groups, and the number of adipocytes in the same field of view was reduced. Compared with the Model group, the adipocytes of mice in the WKB, IF50, IF100 and IF200 groups were smaller and the number of adipocytes in the same field of view was increased.

[0050] The above results indicate that long-term HFD causes an abnormal increase in adipose tissue weight and abnormal adipose tissue morphology in mice; WKB and IF can reduce adipose tissue weight and adipocyte volume in mice and inhibit HFD-induced fat accumulation in mice.

[0051] 5. Effect of IF on liver lipid metabolism disorder of mice induced by HFD The liver is an important organ involved in lipid metabolism, and long-term high-risk liver disease (HFD) can easily cause lipid metabolism disorders in the liver. This study analyzed liver morphology in different groups by observing changes in liver size and color, and examining liver H&E-stained tissue sections. Liver weight, total cholesterol (TC), and triglycerides (TG), as well as liver function indicators AST, ALT, and ALP levels, were measured by observing Oil Red O-stained liver tissue sections to investigate the effects of interferon (IF) on HFD-induced lipid metabolism disorders in mice.

[0052] Effect of IF on liver morphology and tissue morphology of mice induced by HFD Representative liver morphology of each group of mice at week 12 is shown in the figure. Figure 5 (A) As shown in the figure, the liver in the Control group was the smallest, with a smooth surface, a dark red color, and a firm texture. The liver in the Model group was the largest, with an uneven surface and a whitish color. Compared with the Model group, the livers in the WKB, IF50, and IF100 groups were all reduced in size to varying degrees, with a smoother surface and a darker color. The liver morphology in the IF200 group was similar to that of the Model group.

[0053] Liver H&E stained tissue sections of mice in each group at weeks 6 and 12 are shown below. Figure 5 (B) As shown in the figure, the liver tissue cells of mice in the Control group were tightly arranged, structurally intact, and without vacuoles. The liver tissue of mice in the Model group had a large number of vacuoles. At week 6, compared with the Model group, the number of vacuoles in the liver tissues of mice in the WKB, IF50, IF100, and IF200 groups decreased to varying degrees. At week 12, compared with the Model group, the number of vacuoles in the liver tissues of mice in the WKB, IF50, and IF100 groups decreased to varying degrees. The number of vacuoles in the liver tissues of mice in the IF200 group was close to that in the Model group. The number of vacuoles in the liver tissues of mice in the IF50 and IF100 groups remained close to that in the Control group. Compared with week 6, the volume of vacuoles in the liver tissues of mice in the WKB group increased at week 12. This shows that the degree of liver tissue damage in mice in the WKB and IF200 groups changed over time, and the longer the time, the more severe the liver tissue damage. However, the degree of liver tissue damage in mice in the IF50 and IF100 groups did not change much over time.

[0054] The above results indicate that long-term HFD causes liver tissue damage in mice; WKB has no significant effect on improving HFD-induced liver tissue damage in mice in the long term, while IF can effectively improve HFD-induced liver tissue damage in mice in the long term.

[0055] Effect of IF on liver lipid and function of mice induced by HFD Liver weight and liver index of mice in each group at weeks 6 and 12 are shown in the figure. Figure 6 (A) As shown in the figure, at week 6, compared with the control group, the liver weight and liver index of mice in the model group increased significantly (P < 0.05). Compared with the model group, the liver weight and liver index of mice in the WKB, IF50, IF100 and IF200 groups decreased to varying degrees, and the difference in the IF200 group was statistically significant (P < 0.05). At week 12, compared with the control group, the liver weight and liver index of mice in the model group increased significantly (P < 0.05). Compared with the model group, the liver weight and liver index of mice in the WKB, IF50 and IF100 groups decreased, and the difference in the IF50 and IF100 groups was statistically significant (P < 0.05). The liver weight and liver index of mice in the IF200 group were higher than those in the model group.

[0056] The liver TC and TG levels of mice in each group at week 12 are shown in the figure. Figure 6(B) As shown in the figure, compared with the control group, the liver TC and TG content of mice in the model group increased significantly (P < 0.01). Compared with the model group, the liver TC and TG content of mice in the WKB group was higher than that in the model group, while the liver TC and TG content of mice in the IF50 and IF100 groups decreased significantly (P < 0.05). The liver TC and TG content of mice in the IF200 group were similar to those in the model group.

[0057] Serum AST and ALT levels in each group of mice at weeks 6 and 12 are shown in the figure. Figure 6 (CD) As shown in the figure, at week 6, compared with the control group, the serum AST and ALT levels of mice in the model group increased significantly (P < 0.01). Compared with the model group, the serum AST and ALT levels of mice in the WKB, IF50, IF100, and IF200 groups decreased to varying degrees (P < 0.05). At week 12, compared with the control group, the serum AST and ALT levels of mice in the model group increased significantly (P < 0.01). Compared with the model group, the serum AST and ALT levels of mice in the WKB, IF50, and IF100 groups decreased, and the difference between the IF50 and IF100 groups was statistically significant (P < 0.05). The serum AST and ALT levels of mice in the IF200 group were higher than those in the model group.

[0058] Serum ALP levels in each group of mice at weeks 6 and 12 are shown in the figure. Figure 6 (E) As shown in the figure, at week 6, compared with the control group, the serum ALP content of mice in the model group increased significantly (P < 0.01). Compared with the model group, the serum ALP content of mice in the WKB, IF50, IF100 and IF200 groups decreased to varying degrees, and the difference in the IF100 group was statistically significant (P < 0.01). At week 12, compared with the control group, the serum ALP content of mice in the model group increased significantly (P < 0.01). Compared with the model group, the serum ALP content of mice in the WKB, IF50, IF100 and IF200 groups decreased to varying degrees, and the difference in the WKB and IF100 groups was statistically significant (P < 0.05).

[0059] Liver oil red O stained tissue sections of mice in each group at weeks 6 and 12 are shown below. Figure 6(F) As shown in the figure, the livers of mice in the Control group showed no steatosis and almost no lipid droplets, while the livers of mice in the Model group showed a large number of vacuoles and lipid droplets. At week 6, compared with the Model group, the steatosis of the livers of mice in the WKB, IF50, IF100 and IF200 groups all showed varying degrees of improvement. At week 12, compared with the Model group, the steatosis of the livers of mice in the WKB and IF200 groups was similar to that of the Model group, while the steatosis of the livers of mice in the IF50 and IF100 groups showed varying degrees of improvement. This shows that the degree of steatosis of the livers of mice in the WKB and IF200 groups changed over time, with the degree of steatosis becoming more severe over longer periods, while the degree of steatosis of the livers of mice in the IF50 and IF100 groups did not change significantly over time.

[0060] The above results indicate that long-term HFD causes hepatic steatosis and impaired liver function in mice; WKB was not effective in improving HFD-induced hepatic steatosis in mice in the long term, while IF could significantly improve HFD-induced hepatic steatosis and impaired liver function in mice in the long term.

Claims

1. Application of *Cercospora cathartica* mycelium in the preparation of products that improve high-fat diet (HFD)-induced glucose and lipid metabolism disorders.

2. The application according to claim 1, characterized in that: The strain selected for the *Cercospora cateri* was the strain with the preservation number CGMCCNO.0706.

3. The application according to claim 2, characterized in that, The method for preparing *Cercospora cathartica* mycelium includes: Prepare a solid culture medium using millet, sucrose, MgSO4, KH2PO4, and distilled water; The solid culture medium was sterilized at 120℃-130℃ and cooled to room temperature before being inoculated with *Cyclophorus cirrhosa*. The inoculated culture flasks were then placed in an environment with a temperature of 20℃-25℃ and a relative humidity of 40%-60% for fermentation. After the mycelium had covered the entire culture flask, the culture was collected and dried in a drying oven into mycelial blocks. The blocks were then pulverized into powder and sieved to obtain *Cyclophorus cirrhosa* mycelium for later use.

4. The application according to claim 3, characterized in that, The solid culture medium mentioned above, by mass parts, includes 830-850 parts millet, 40-45 parts sucrose, 2.5-3.0 parts MgSO4, and 5.0-6.0 parts KH2PO4.

5. The application according to claim 4, characterized in that, By mass, it includes 840 parts millet, 42 parts sucrose, 2.8 parts MgSO4, and 5.5 parts KH2PO4.

6. The application according to claim 1, characterized in that: The product includes at least one of the following: medicine, health product, and food.

7. The application according to claim 1, characterized in that, The *Cercospora cateri* mycelium improves high-fat diet (HFD)-induced glucose and lipid metabolism disorders through at least one of the following mechanisms: (1) Improve glucose tolerance and insulin sensitivity, and inhibit hyperglycemia induced by high-fat diet (HFD); (2) Improve lipid metabolism abnormalities induced by high-fat diet (HFD); (3) Inhibits fat accumulation induced by high-fat diet (HFD); (4) Prevent liver tissue damage induced by high-fat diet (HFD); (5) Prevent high-fat diet (HFD)-induced liver lipid deposition and hepatic steatosis, and improve liver lipid metabolism function.

8. A drug for treating and preventing disorders of glucose and lipid metabolism, characterized in that: Its active ingredient includes the mycelium of *Cercospora cateri* as described in claim 1.

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