Application of compound fat powder in preparation of products for treating or improving obesity

Abstract

The invention provides application of compound fat powder in preparation of products for treating or improving obesity, and belongs to the technical field of biological medicine. The invention provides an application of composite fat powder in preparation of a product for treating or improving obesity, the composite fat powder comprises coconut oil, linseed oil and safflower seed oil, and the weight ratio of the coconut oil to the linseed oil to the safflower seed oil is (12-18): (8-12): (6-12). The invention finds that the compound fat powder CFP has positive influence on the aspects of body weight, liver and adipose tissue, blood fat, blood sugar level, liver function, gallbladder function, lipid metabolism, kidney function, insulin and the like, and also finds that the CFP intervenes in obesity through the synergistic effect of multiple components, multiple targets and multiple pathways. The invention provides thoughts and strategies for clinical treatment of obesity and related metabolic syndromes caused by high-fat diet.

Description

Technical Field

[0001] The present invention belongs to the field of biomedical technology, and particularly relates to the application of a compound fat powder in the preparation of products for treating or improving obesity. Background Art

[0002] Obesity and related metabolic syndromes have become global public health problems. Existing intervention programs mainly include drug treatment, dietary replacement, fat metabolism blockade, etc., but all have significant limitations.

[0003] Although chemical drugs such as orlistat and GLP-1 receptor agonists can achieve weight loss by inhibiting fat absorption or regulating appetite, long-term use is prone to serious side effects. For example, orlistat may cause fat-soluble vitamin deficiency and steatorrhea; GLP-1 drugs (such as semaglutide) have gastrointestinal reactions and cardiovascular risks. Such drugs mostly target specific targets, are difficult to improve metabolic disorders through multi-pathway coordination, and require strict prescription restrictions, resulting in low patient compliance.

[0004] Meal replacement products such as high-protein powder and dietary fiber supplements rely on calorie control and can achieve weight loss in the short term, but the long-term effect is significantly affected by individual metabolic differences and fails to solve the fundamental problem of abnormal fat accumulation. In addition, existing meal replacements are prone to cause users to give up halfway due to insufficient taste and nutritional balance.

[0005] Chitosan and activated carbon block absorption by binding dietary fat, but have problems of poor targeting and affecting the absorption of fat-soluble nutrients. Taking chitosan as an example, its adsorption efficiency for saturated fat is less than 30%, and it may cause discomfort such as abdominal distension and constipation. There are no relevant reports in the prior art on using compound fat powder to intervene in obesity and related metabolic syndromes. Summary of the Invention

[0006] The purpose of the present invention is to provide the application of a compound fat powder in the preparation of products for treating or improving obesity.

[0007] In order to achieve the above purpose, the present invention provides the following technical solutions:

[0008] The present invention provides the application of a compound fat powder in the preparation of products for treating or improving obesity, wherein the compound fat powder includes coconut oil, linseed oil and safflower oil, and the mass ratio of coconut oil, linseed oil and safflower oil is (12-18):(8-12):(6-12).

[0009] Preferably, the compound fat powder comprises coconut oil, linseed oil, safflower oil, resistant dextrin, maltitol oligosaccharide, casein, isomaltooligosaccharide, mono- and diglycerol fatty acid esters, sodium octenyl succinate starch, potassium citrate, sodium ascorbate and silicon dioxide, and the mass ratio of coconut oil, linseed oil, safflower oil, resistant dextrin, maltitol oligosaccharide, casein, isomaltooligosaccharide, mono- and diglycerol fatty acid esters, sodium octenyl succinate starch, potassium citrate, sodium ascorbate and silicon dioxide is (12 - 18):(8 - 12):(6 - 12):(15 - 22):(8 - 14):(8 - 12):(6 - 10):(1 - 2):(2 - 4):(0.25 - 0.75):(0.25 - 0.75):(1 - 2).

[0010] Preferably, the preparation method of the compound fat powder comprises the following steps:

[0011] (1) Preparation of oil phase: Mix the coconut oil, linseed oil and safflower oil by heating and stirring;

[0012] (2) Preparation of water phase: Add resistant dextrin, maltitol oligosaccharide, casein and isomaltooligosaccharide into water, and heat and stir to mix;

[0013] (3) Primary emulsification: Slowly add the oil phase into the water phase in a high-shear emulsifier for shear emulsification to obtain a preliminary emulsion;

[0014] (4) Homogenization: Homogenize the primary emulsion 3 - 5 times to obtain a microcapsule emulsion;

[0015] (5) Adding emulsifier and wall material: Shear and stir the microcapsule emulsion with mono- and diglycerol fatty acid esters and sodium octenyl succinate starch to obtain an embedded microcapsule emulsion;

[0016] (6) Spray drying: Spray dry the embedded microcapsule emulsion to obtain microcapsule powder;

[0017] (7) Mixing: Mix the microcapsule powder obtained by spray drying with potassium citrate, sodium ascorbate and silicon dioxide to obtain the compound fat powder.

[0018] Preferably, the compound fat powder can reduce body weight, the obesity includes obesity caused by high-fat diet, and the product includes drugs.

[0019] The present invention also provides an application of the compound fat powder in the preparation of a product for reducing liver weight and / or adipose tissue weight.

[0020] The present invention also provides an application of the compound fat powder in the preparation of a product for treating or improving abnormal blood lipid levels caused by obesity and / or in the preparation of a product for treating or improving abnormal blood glucose levels caused by obesity.

[0021] The present invention also provides an application of the composite fat powder in the preparation of a product for treating or improving liver function abnormalities caused by obesity.

[0022] The present invention also provides an application of the composite fat powder in the preparation of a product for treating or improving gallbladder function abnormalities caused by obesity.

[0023] The present invention also provides an application of the composite fat powder in the preparation of a product for treating or improving lipid metabolism disorders caused by obesity.

[0024] The present invention also provides an application of the composite fat powder in the preparation of a product for treating or improving abnormal insulin secretion caused by obesity and / or in the preparation of a product for treating or improving kidney function abnormalities caused by obesity.

[0025] Preferably, the effective dose of the composite fat powder for treating or improving obesity is > 0.6 g / kg.

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] The composite fat powder of the present invention includes coconut oil, linseed oil and safflower oil, and the mass ratio of the coconut oil, linseed oil and safflower oil is (12 - 18):(8 - 12):(8 - 12). The present invention discovers that the composite fat powder (CFP) has corresponding positive effects on body weight, liver and adipose tissue, blood lipid, blood glucose level, liver function, gallbladder function, lipid metabolism, kidney function and insulin, etc., and can be applied to the preparation of products for treating or improving obesity-related problems. The present invention also discovers that CFP intervenes in obesity through the synergistic action of multiple components, multiple targets and multiple pathways, providing an efficient new pharmaceutical preparation for the clinical research of obesity and related metabolic syndromes caused by high-fat diet.

[0028] The composite fat powder of the present invention includes coconut oil, linseed oil and safflower oil, and the mass ratio of the coconut oil, linseed oil and safflower oil is (12 - 18):(8 - 12):(8 - 12). Through network pharmacology analysis of the composite fat powder, the intersection of the target genes of the active ingredients of CFP and the target genes of obesity is taken to obtain the intersection targets, which are the common targets of the drug and the disease; GO function enrichment analysis and KEGG pathway enrichment analysis are performed on the selected intersection targets, and finally a "key component - potential target - core pathway" network is obtained. The results of network pharmacology analysis show that CFP may play an anti-obesity role through multiple pathways, and the insulin resistance pathway may play a key role. By the synergistic treatment effect of multiple components, multiple targets and multiple pathways, it provides ideas and strategies for the clinical treatment of obesity and related metabolic syndromes caused by high-fat diet. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1Results of particle size and Zeta potential determination of the compound fat powder in Example 1; among them, A is the result of particle size determination of the compound fat powder; B is the result of Zeta potential determination of the compound fat powder.

[0030] Figure 2 Scanning electron microscope images of the compound fat powder in Example 1; among them, A is 400×, B is 1000×, and C is 4000×.

[0031] Figure 3 Results of thermogravimetric analysis TGA curve of the compound fat powder in Example 1.

[0032] Figure 4 Fourier transform infrared spectroscopy analysis diagram of the compound fat powder in Example 1.

[0033] Figure 5 X-ray diffraction pattern of the compound fat powder in Example 1.

[0034] Figure 6 Venn diagram of the intersection targets of the main components of the compound fat powder and obesity in Example 4.

[0035] Figure 7 Component-target network diagram in Example 4. Among them, diamonds represent chemical components; circles represent component-related targets.

[0036] Figure 8 Results of constructing the PPI interaction network of the intersection targets of drugs and diseases in Example 4.

[0037] Figure 9 Results of GO and KEGG pathway enrichment analysis in Example 4, where A is the GO pathway enrichment analysis diagram, B is the bar chart of the number of genes involved in different functions, C is the KEGG pathway enrichment analysis diagram, and D is the pathway diagram of the insulin resistance signaling pathway.

[0038] Figure 10 Key component-potential target-core pathway network diagram in Example 4.

[0039] Figure 11 Results of molecular docking in Example 4, where A is the molecular docking analysis result of the target protein and the compound fat powder, and B is the molecular docking clustering heat map.

[0040] Figure 12 Results of the effects of CFP on the body weight, liver and adipose tissue weights and morphology of rats in Example 4, where A is the body weight change, B is the Lee’s index, C is the food intake, D is the liver weight, E is the liver coefficient, F is the epididymal fat coefficient, and G is the body fat rate.

[0041] Figure 13Results of the effects of CFP on blood lipid and blood glucose levels in rats in Example 4, where A is total cholesterol, B is triglyceride, C is high-density lipoprotein cholesterol, D is low-density lipoprotein cholesterol, and E is glucose.

[0042] Figure 14 Effects of CFP on indexes related to liver function in rats in Example 4, where A is aspartate aminotransferase, B is alanine aminotransferase, and C is lactate dehydrogenase.

[0043] Figure 15 Effects of CFP on indexes related to bile function in rats in Example 4, where A is albumin, B is total bile acid, and C is total protein.

[0044] Figure 16 Effects of CFP on levels of indexes related to lipid metabolism in rats in Example 4, where A is leptin, B is lipoprotein lipase, and C is hepatic lipase.

[0045] Figure 17 Effects of CFP on levels of indexes related to renal function and insulin in rats in Example 4, where A is creatinine, B is uric acid, and C is insulin.

[0046] Figure 18 HE staining results of rat liver tissue in Example 4.

[0047] Figure 19 HE staining results of rat adipose tissue in Example 4. Detailed implementation manners

[0048] The present invention provides an application of a compound fat powder in the preparation of a product for treating or improving obesity. The compound fat powder includes coconut oil, linseed oil, and safflower oil, and the mass ratio of coconut oil, linseed oil, and safflower oil is (12 - 18):(8 - 12):(6 - 12).

[0049] In the present invention, coconut oil, linseed oil, and safflower oil act as main active ingredients. The mass ratio of coconut oil, linseed oil, and safflower oil is preferably (14 - 16):(9 - 11):(7 - 11), and further preferably 15:10:8.

[0050] More preferably, the compound fat powder comprises coconut oil, linseed oil, safflower oil, resistant dextrin, maltitol oligosaccharide, casein, isomaltooligosaccharide, mono- and diglycerol fatty acid esters, sodium starch octenyl succinate, potassium citrate, sodium ascorbate and silicon dioxide, and the mass ratio of coconut oil, linseed oil, safflower oil, resistant dextrin, maltitol oligosaccharide, casein, isomaltooligosaccharide, mono- and diglycerol fatty acid esters, sodium starch octenyl succinate, potassium citrate, sodium ascorbate and silicon dioxide is (12-18):(8-12):(6-12):(15-22):(8-14):(8-12):(6-10):(1-2):(2-4):(0.25-0.75):(0.25-0.75):(1-2). As an alternative embodiment, the mass ratio of coconut oil, linseed oil, safflower oil, resistant dextrin, maltitol oligosaccharide, casein, isomaltooligosaccharide, mono- and diglycerol fatty acid esters, sodium starch octenyl succinate, potassium citrate, sodium ascorbate and silicon dioxide is 12:8:6:15:8:8:6:1:2:0.25:0.25:1 or 18:12:12:22:14:12:10:2:4:0.75:0.75:2 or 15:10:8:20:12:10:8:1.5:3:0.5:0.5:1.5.

[0051] In the present invention, the preparation method of the compound fat powder comprises the following steps:

[0052] (1) Preparation of oil phase: Mix coconut oil, linseed oil and safflower oil by heating, shearing and stirring;

[0053] (2) Preparation of water phase: Add resistant dextrin, maltitol oligosaccharide, casein and isomaltooligosaccharide to water, and heat and stir to mix;

[0054] (3) Primary emulsification: Slowly add the oil phase to the water phase in a high-shear emulsifier for shearing emulsification to obtain a preliminary emulsion;

[0055] (4) Homogenization: Homogenize the preliminary emulsion 3-5 times to obtain a microcapsule emulsion;

[0056] (5) Adding emulsifier and wall material: Shear and stir the microcapsule emulsion with mono- and diglycerol fatty acid esters and sodium starch octenyl succinate to obtain an embedded microcapsule emulsion;

[0057] (6) Spray drying: Spray dry the embedded microcapsule emulsion to obtain microcapsule powder;

[0058] (7) Mixing: Mix the microcapsule powder obtained by spray drying with potassium citrate, sodium ascorbate and silicon dioxide to obtain the compound fat powder.

[0059] When preparing the composite fat powder of the present invention, the stability of the emulsion and the microencapsulation effect are improved through steps such as oil phase preparation, water phase preparation, primary emulsification, homogenization, and addition of emulsifier and wall material.

[0060] In the oil phase preparation step of the composite fat powder of the present invention, coconut oil, linseed oil, and safflower oil are mixed according to a mass ratio of (12 - 18):(8 - 12):(6 - 12), preferably 15:10:8. The coconut oil, linseed oil, and safflower oil serve as the oil phase raw materials. After mixing the above oil phase raw materials, they are heated to 50°C - 60°C, the stirring speed is 500 rpm - 800 rpm, and the stirring time is 10 - 15 minutes. Further preferably, it is heated to 55°C, the stirring speed is 650 rpm, and the stirring time is 12.5 minutes.

[0061] Before the oil phase preparation step of the composite fat powder of the present invention, pretreatment of the oil phase raw materials is carried out. The oil phase raw materials include coconut oil, linseed oil, and safflower oil.

[0062] In the present invention, the pretreatment step of the oil phase raw materials includes:

[0063] Coconut oil, linseed oil, and safflower oil are respectively fed into a degumming device, heated at 60°C - 80°C, 0.1% - 0.3% of phosphoric acid or citric acid is added, and stirred for 10 - 15 minutes to hydrolyze the colloidal substances, and then left to stand for sedimentation or a centrifuge is used to remove the colloid to obtain degummed oil. The heating temperature is preferably 70°C. When degumming, phosphoric acid is preferably added, and the dosage is 0.2% of the mass of the oil phase raw materials, and stirred for 12.5 minutes.

[0064] The degummed oil is fed into a deacidification device, 0.1% - 0.3% of sodium hydroxide or sodium carbonate is added, and stirred for 10 - 15 minutes to neutralize the free fatty acids to form soap stock, and then left to stand for sedimentation or a centrifuge is used to remove the soap stock to obtain deacidified oil. When deacidifying, sodium hydroxide is preferably added, and the dosage is 0.2% of the mass of the degummed oil, and stirred for 12.5 minutes.

[0065] The deacidified oil is fed into a decolorization device, 0.5% - 1.0% of activated carbon or clay is added, and stirred for 20 - 30 minutes to adsorb the pigments and odor substances in the oil, and then a filtration device is used to filter and remove the adsorbent. When decolorizing, the dosage of activated carbon is preferably 0.8% of the mass of the deacidified oil, and stirred for 25 minutes.

[0066] The decolorized oil is fed into a deodorization device, and vacuum distillation is carried out at 180°C - 200°C, the vacuum degree is 0.1 MPa - 0.3 MPa, and the time is 20 - 40 minutes to remove the odor substances in the oil. When deodorizing, the vacuum distillation temperature is preferably 190°C, the vacuum degree is preferably 0.2 MPa, and the time is preferably 30 minutes.

[0067] In the present invention, after the above-mentioned pretreatment of the aqueous material, the aqueous phase preparation step is carried out.

[0068] In the aqueous phase preparation step of the composite fat powder of the present invention, resistant dextrin, maltitol oligosaccharide, casein, and isomaltooligosaccharide are mixed in a mass ratio of (18-20):(10-12):(10-12):(8-10), added to water, heated to 60°C - 70°C in a stirring tank, and stirred at a speed of 1000 rpm - 1500 rpm using a high-speed shear stirrer for 30 minutes - 45 minutes until completely dissolved.

[0069] In the present invention, the mass parts of the resistant dextrin, maltitol oligosaccharide, casein, and isomaltooligosaccharide are preferably 20:12:10:8. The resistant dextrin, maltitol oligosaccharide, casein, and isomaltooligosaccharide are aqueous phase raw materials, and the weight-volume ratio of the total amount of the aqueous phase raw materials to water is 10:(3-6) (kg / L), preferably 10:4.5 (kg / L). In the aqueous phase preparation step, the heating is further preferably 65°C, the stirring speed is more preferably 1250 rpm, and the stirring time is more preferably 37.5 minutes.

[0070] In the primary emulsification step of the composite fat powder of the present invention, in a high-shear emulsifier, the oil phase is slowly added to the aqueous phase, and high-speed shear emulsification is carried out at 50°C - 60°C with a shear speed of 8000 rpm - 12000 rpm for 10 minutes - 15 minutes to form a preliminary emulsion. Among them, the high-speed shear emulsification temperature is preferably 55°C, the shear speed is preferably 10000 rpm, and the emulsification time is preferably 12.5 minutes.

[0071] In the homogenization step of the composite fat powder of the present invention, the primary emulsion is fed into a homogenizing emulsifier for high-pressure homogenization. The homogenization pressure is 30 MPa - 50 MPa, and the number of homogenization times is 3 - 5 times to ensure the stability of the emulsion and form a uniform microcapsule emulsion. Among them, the homogenization pressure is preferably 40 MPa, and the number of homogenization times is preferably 4 times.

[0072] When adding the emulsifier and wall material to the composite fat powder of the present invention: in a stirring tank, the microcapsule emulsion is mixed with mono- and diglycerol fatty acid esters and sodium octenyl succinate starch. Stir at a speed of 500 rpm - 800 rpm using a high-speed shear stirrer for 10 minutes - 15 minutes to further improve the stability of the emulsion and the microencapsulation effect. Among them, the weight parts of the mono- and diglycerol fatty acid esters and sodium octenyl succinate starch are (1-2):(2-4), further preferably 1.5:3. When stirring, the stirring speed is preferably 650 rpm, and the stirring time is preferably 12.5 minutes.

[0073] In the present invention, during the spray drying step of the composite fat powder, the inlet air temperature is controlled to be 150°C to 180°C, the outlet air temperature is 80°C to 90°C, and the atomization pressure is 25 to 30 MPa. As an alternative embodiment, the inlet air temperature is preferably 165°C, the outlet air temperature is preferably 85°C, and the atomization pressure is preferably 28 MPa. During the spray drying of the present invention, the encapsulated microcapsule emulsion is atomized into uniform and fine droplets by a centrifugal atomizer, so that the water in the emulsion evaporates rapidly to form microcapsule powder. A cyclone separator is used to collect the dried microcapsule powder, improving the product yield and purity. For the microcapsule powder that cannot be completely collected, a bag filter is used for further collection to ensure the product purity.

[0074] In the mixing step of the composite fat powder in the present invention: the microcapsule powder obtained by spray drying is mixed with potassium citrate, sodium ascorbate, and silicon dioxide to obtain the composite fat powder. The weight parts of potassium citrate, sodium ascorbate, and silicon dioxide are (0.25 to 0.75):(0.25 to 0.75):(1 to 2), preferably 0.5:0.5:1.5. When mixing, the mixing speed is 500 rpm to 800 rpm, and the mixing time is 15 minutes to 30 minutes; the mixing speed is preferably 650 rpm, and the mixing time is preferably 22.5 minutes. The mixing ensures that each component is fully and evenly mixed, ensuring the uniform distribution of potassium citrate, sodium ascorbate, and silicon dioxide in the microcapsule powder.

[0075] In the present invention, before the water phase preparation step of the water phase raw material, a pretreatment of the water phase raw material is carried out, and the treatment steps include:

[0076] Resistant dextrin, maltodextrin, casein, and isomaltooligosaccharide are respectively placed in a vibrating screen, the screen aperture is adjusted to 40 mesh to 80 mesh, the vibration frequency is 50 Hz to 100 Hz, and the amplitude is 2 mm to 5 mm for sieving to remove large particles and impurities. Among them, the screen aperture is preferably 60 mesh, the vibration frequency is preferably 75 Hz, and the amplitude is preferably 3.5 mm.

[0077] In the present invention, before preparing the composite fat powder, potassium citrate, mono- and diglycerol fatty acid esters, sodium starch octenyl succinate, sodium ascorbate, and silicon dioxide are respectively placed in a rotary vibrating screen, the screen aperture is adjusted to 80 mesh to 120 mesh, and the rotation speed is 1000 rpm to 2000 rpm for sieving to ensure that the particles are fine and uniform, facilitating subsequent mixing and dispersion. Among them, the screen aperture is preferably 100 mesh, and the rotation speed is preferably 1500 rpm.

[0078] In the present invention, the obesity includes obesity caused by a high-fat diet. In the present invention, intragastric administration of the compound fat powder to a rat obesity model caused by a high-fat diet can effectively reduce the body weight of the rat obesity model, reduce the liver weight and / or adipose tissue weight, lower the blood lipid level and blood glucose level, and have a positive response to liver function, gallbladder function, kidney function, lipid metabolism, and insulin secretion.

[0079] In the present invention, the product is a medicine. When used as a medicine, the effective dose of the compound fat powder for treating or improving obesity is >0.6 g / kg.

[0080] In the present invention, the compound fat powder can reduce body weight. As an implementable embodiment, intragastric administration of the compound fat powder to a rat obesity model caused by a high-fat diet can effectively reduce the body weight of the rat obesity model.

[0081] In the present invention, the compound fat powder can effectively treat or improve obesity, and its effect is better than semaglutide in a certain amount.

[0082] The present invention also provides an application of a compound fat powder in the preparation of a product for reducing the liver weight and / or adipose tissue weight caused by obesity. In the present invention, the compound fat powder can reduce the liver weight and / or adipose tissue weight of a rat obesity model caused by a high-fat diet.

[0083] The present invention also provides an application of a compound fat powder in the preparation of a product for improving abnormal blood lipid levels caused by obesity and / or improving abnormal blood glucose levels caused by obesity. In the present invention, the compound fat powder can reduce the total cholesterol content, triglyceride content, high-density lipoprotein cholesterol content, and low-density lipoprotein cholesterol content to improve the abnormal blood lipid levels caused by obesity and reduce the glucose content to improve the abnormal blood glucose levels caused by obesity.

[0084] The present invention also provides an application of a compound fat powder in the preparation of a product for improving abnormal liver function caused by obesity. In the present invention, the compound fat powder can reduce the expression levels of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase to improve the abnormal liver function caused by obesity.

[0085] The present invention also provides an application of a compound fat powder in the preparation of a product for improving abnormal gallbladder function caused by obesity. In the present invention, the compound fat powder can reduce the expression levels of albumin, total bile acid, and total protein to improve the abnormal gallbladder function caused by obesity.

[0086] The present invention also provides an application of a compound fat powder in the preparation of a product for improving abnormal lipid metabolism caused by obesity. In the present invention, the compound fat powder can reduce the expression level of leptin and increase the expression levels of lipoprotein lipase and hepatic lipase to improve the abnormal lipid metabolism caused by obesity.

[0087] The present invention also provides the use of a compound fat powder in the preparation of a product for improving insulin secretion disorders caused by obesity and / or renal function disorders caused by obesity.

[0088] Unless otherwise specified, the test methods used in the following examples are all conventional test methods; the materials, reagents, etc. used, unless otherwise specified, are reagents and materials that can be obtained from commercial channels.

[0089] The equipment and models used in the following examples are: hydration tank, model LYY120; alkali refining tank, model 1730; decolorization tank, model JL-2-500; deodorization tank, model JL-2-500; centrifuge, model ZYDB21SJ-34.

[0090] In the following examples, the experimental animals: 90 six-week-old male SD rats were purchased from Beijing Speifo Biotechnology Co., Ltd., license number: SYXK (Qing) 2022—0001. All animals were housed in an SPF laboratory at a temperature of 22 ± 1 °C, a relative humidity of 60%-70%, a light and dark cycle of 12 h, and free access to water. The animal experiments in this study have been approved by the Experimental Animal Ethics Committee of the Northwest Institute of Plateau Biology, Chinese Academy of Sciences (batch number: NWIPB20171106-01).

[0091] In the experimental data results of the accompanying drawings of the following examples, ns indicates that P > 0.05 means no statistically significant difference, *P < 0.05 means a statistically significant difference, and **P < 0.01 means a highly statistically significant difference.

[0092] Next, the technical solutions in the present invention will be clearly and completely described in conjunction with the examples in the present invention.

[0093] Example 1

[0094] 1. Preparation of compound fat powder

[0095] 1.1 Formula of compound fat powder

[0096] It is made from raw materials in the following weight ratios:

[0097] Oil phase: 15 kg of coconut oil, 10 kg of linseed oil, 8 kg of safflower oil; water phase: 20 kg of resistant dextrin, 12 kg of maltitol, 10 kg of casein, 8 kg of isomaltooligosaccharide, 22.5 L of water; 1.5 kg of mono- and diglycerol fatty acid esters; 3 kg of octenyl succinic anhydride starch sodium; 0.5 kg of potassium citrate; 0.5 kg of sodium ascorbate; 1.5 kg of silicon dioxide.

[0098] 1.2 Preparation method of compound fat powder

[0099] The steps are as follows:

[0100] (1) Pretreatment of oil-phase component materials:

[0101] Send coconut oil, linseed oil, and safflower oil into a degumming device (hydration tank) respectively, heat at 70 °C, add 0.2% phosphoric acid, stir for 12.5 minutes to hydrolyze the colloidal substances, then let it stand for sedimentation to remove the colloids and obtain degummed oil.

[0102] Send the degummed oil into a deacidification device (caustic refining tank), add 0.2% sodium hydroxide, stir for 12.5 minutes to neutralize the free fatty acids and form soapstock, then let it stand for sedimentation to remove the soapstock and obtain deacidified oil.

[0103] Send the deacidified oil into a decolorization device (decolorization tank), add 0.75% activated carbon, stir for 25 minutes to adsorb the pigments and odor substances in the oil, then use a filtering device to filter out the adsorbent and obtain decolorized oil.

[0104] Send the decolorized oil into a deodorization device (deodorization tank), carry out vacuum distillation at 190 °C, with a vacuum degree of 0.2 MPa and a time of 30 minutes to remove the odor substances in the oil, and obtain refined coconut oil, linseed oil, and safflower oil respectively.

[0105] (2) Pretreatment of water-phase component materials

[0106] Put resistant dextrin, maltitol oligosaccharide, casein, and isomaltooligosaccharide into a vibrating screen respectively, adjust the screen aperture to 60 mesh, the vibration frequency to 75 Hz, and the amplitude to 3.5 mm, and carry out sieving to remove large particles and impurities, and obtain treated resistant dextrin, maltitol oligosaccharide, casein, and isomaltooligosaccharide.

[0107] Put potassium citrate, mono- and diglycerol fatty acid esters, sodium starch octenyl succinate, sodium ascorbate, and silicon dioxide into a rotary vibrating screen respectively, adjust the screen aperture to 100 mesh, and the rotation speed to 1500 rpm, and carry out sieving to ensure that the particles are small and uniform, and obtain treated potassium citrate, mono- and diglycerol fatty acid esters, sodium starch octenyl succinate, sodium ascorbate, and silicon dioxide, which is convenient for subsequent mixing and dispersion.

[0108] (3) Microencapsulation

[0109] Preparation of oil phase: Mix 15 kg of refined coconut oil, 10 kg of linseed oil, and 8 kg of safflower oil. Heat to 55 °C in a stirring tank, and use a high-speed shear stirrer to stir evenly at a speed of 650 rpm for 12.5 minutes.

[0110] Aqueous phase preparation: Mix the treated 20 kg of resistant dextrin, 12 kg of maltodextrin, 10 kg of casein, and 8 kg of isomaltooligosaccharide, add 22.5 L of water, heat to 65 °C in a stirring tank, stir with a high-speed shear stirrer at a speed of 1250 rpm for 37.5 minutes until completely dissolved.

[0111] Primary emulsification: Slowly add the oil phase to the aqueous phase in a high-shear emulsifier, perform high-speed shear emulsification at 55 °C, with a shear speed of 10000 rpm and an emulsification time of 12.5 minutes to form a primary emulsion.

[0112] Homogenization: Feed the primary emulsion into a homogenizing emulsifier for high-pressure homogenization. The homogenization pressure is 40 MPa and the number of homogenization times is 4 to ensure the stability of the emulsion and form a uniform microcapsule emulsion.

[0113] Add emulsifier and wall material: In a stirring tank, mix the microcapsule emulsion with 1.5 kg of mono- and diglycerol fatty acid esters and 3 kg of sodium octenyl succinate starch. Stir with a high-speed shear stirrer at a speed of 650 rpm for 12.5 minutes to further improve the stability of the emulsion and the microencapsulation effect, obtaining a microencapsulated emulsion.

[0114] (4) Spray drying of the microencapsulated emulsion

[0115] Feed the microcapsule emulsion into a spray drying tower, atomize the emulsion into uniform and fine droplets through a centrifugal atomizer, control the inlet air temperature at 165 °C, the outlet air temperature at 85 °C, and the atomization pressure at 28 MPa to rapidly evaporate the water in the emulsion and form microcapsule powder.

[0116] Use a cyclone separator to collect the dried microcapsule powder to improve the product yield and purity.

[0117] For the microcapsule powder that cannot be completely collected, use a bag filter for further collection to ensure the purity of the product.

[0118] (5) Mixing

[0119] According to the production scale and product characteristics, select a horizontal mixer. Mix the microcapsule powder obtained by spray drying with 0.5 kg of potassium citrate, 0.5 kg of sodium ascorbate, and 1.5 kg of silicon dioxide in the mixer. Control the mixing speed at 650 rpm and the mixing time at 22.5 minutes to ensure that each component is fully and evenly mixed, ensuring the uniform distribution of potassium citrate, sodium ascorbate, and silicon dioxide in the microcapsule powder. The product obtained after uniform mixing is the final compound fat powder.

[0120] Example 2

[0121] 1. Preparation of compound fat powder

[0122] 1.1 Formulation of compound fat powder

[0123] It is made from raw materials with the following weight ratios:

[0124] Oil phase: 12 kg of coconut oil, 8 kg of linseed oil, 6 kg of safflower oil; water phase: 15 kg of resistant dextrin, 8 kg of maltitol, 8 kg of casein, 6 kg of isomaltooligosaccharide, 11.1 L of water; 1 kg of mono- and diglycerol fatty acid ester; 2 kg of sodium starch octenyl succinate; 0.25 kg of potassium citrate; 0.25 kg of sodium ascorbate; 1 kg of silicon dioxide.

[0125] 1.2 Preparation method of compound fat powder

[0126] The steps are as follows:

[0127] (1) Pretreatment of oil phase component materials:

[0128] Respectively send coconut oil, linseed oil and safflower oil into a degumming device (hydration tank), heat at 60 °C, add 0.1% phosphoric acid, stir for 10 minutes to hydrolyze the colloidal substances, and then let it stand for sedimentation to remove the colloid to obtain degummed oil.

[0129] Send the degummed oil into a deacidification device (caustic refining tank), add 0.1% sodium hydroxide, stir for 10 minutes to neutralize the free fatty acids to form soapstock, and then let it stand for sedimentation to remove the soapstock to obtain deacidified oil.

[0130] Send the deacidified oil into a decolorization device (decolorization tank), add 0.5% activated carbon, stir for 20 minutes to adsorb the pigments and odor substances in the oil, and then use a filtering device to filter out the adsorbent to obtain decolorized oil.

[0131] Send the decolorized oil into a deodorization device (deodorization tank), carry out vacuum distillation at 180 °C, with a vacuum degree of 0.1 MPa and a time of 20 minutes to remove the odor substances in the oil, and respectively obtain refined coconut oil, linseed oil and safflower oil.

[0132] (2) Pretreatment of water phase component materials

[0133] Respectively put resistant dextrin, maltitol, casein, and isomaltooligosaccharide into a vibrating screen, adjust the screen aperture to 40 mesh, the vibration frequency to 50 Hz, and the amplitude to 2 mm for sieving to remove large particles and impurities, and obtain treated resistant dextrin, maltitol, casein, and isomaltooligosaccharide.

[0134] Put potassium citrate, mono- and diglycerides of fatty acids, sodium starch octenyl succinate, sodium ascorbate, and silicon dioxide into a vibratory sieve respectively. Adjust the sieve aperture to 80 mesh and the rotation speed to 1000 rpm for sieving to ensure that the particles are small and uniform, obtaining the treated potassium citrate, mono- and diglycerides of fatty acids, sodium starch octenyl succinate, sodium ascorbate, and silicon dioxide, which is convenient for subsequent mixing and dispersion.

[0135] (3) Microencapsulation

[0136] Preparation of the oil phase: Mix 12 kg of refined coconut oil, 8 kg of linseed oil, and 6 kg of safflower oil. Heat it to 50 °C in a stirring tank and stir evenly at a speed of 500 rpm using a high-speed shear stirrer for 10 minutes.

[0137] Preparation of the water phase: Mix the treated 15 kg of resistant dextrin, 8 kg of maltodextrin, 8 kg of casein, and 6 kg of isomaltooligosaccharide, add 11.1 L of water, heat it to 60 °C in a stirring tank, stir at a speed of 1000 rpm using a high-speed shear stirrer for 30 minutes until completely dissolved.

[0138] Primary emulsification: Slowly add the oil phase to the water phase in a high-shear emulsifier, carry out high-speed shear emulsification at 50 °C, with a shear speed of 8000 rpm and an emulsification time of 10 minutes to form a primary emulsion.

[0139] Homogenization: Feed the primary emulsion into a homogenizing emulsifier for high-pressure homogenization. The homogenization pressure is 30 MPa and the number of homogenization times is 3 times to ensure the stability of the emulsion and form a uniform microcapsule emulsion.

[0140] Add emulsifier and wall material: In a stirring tank, mix the microcapsule emulsion with 1 kg of mono- and diglycerides of fatty acids and 2 kg of sodium starch octenyl succinate, stir at a speed of 500 rpm using a high-speed shear stirrer for 10 minutes to further improve the stability of the emulsion and the microencapsulation effect, obtaining a microencapsulated emulsion.

[0141] (4) Spray drying of the microencapsulated emulsion

[0142] Feed the microencapsulated emulsion into a spray drying tower, atomize the emulsion into uniform and fine droplets through a centrifugal atomizer, control the inlet air temperature at 150 °C, the outlet air temperature at 80 °C, and the atomization pressure at 25 MPa to rapidly evaporate the water in the emulsion and form microcapsule powder.

[0143] Use a cyclone separator to collect the dried microcapsule powder to improve the yield and purity of the product.

[0144] For the microcapsule powder that cannot be completely collected, use a bag filter for further collection to ensure the purity of the product.

[0145] (5) Mixing

[0146] According to the production scale and product characteristics, a horizontal mixer is selected. The microcapsule powder obtained by spray drying is mixed with 0.25 kg of potassium citrate, 0.25 kg of sodium ascorbate, and 1 kg of silicon dioxide in the mixer. The mixing speed is controlled at 500 rpm and the mixing time is 15 minutes to ensure that all components are fully and evenly mixed, and to ensure that potassium citrate, sodium ascorbate, and silicon dioxide are evenly distributed in the microcapsule powder. The product obtained after uniform mixing is the final compound fat powder.

[0147] Example 3

[0148] 1. Preparation of Compound Fat Powder

[0149] 1.1 Formula of Compound Fat Powder

[0150] It is made from raw materials with the following weight ratios:

[0151] Oil phase: 18 kg of coconut oil, 12 kg of linseed oil, 12 kg of safflower oil; water phase: 22 kg of resistant dextrin, 14 kg of maltitol oligosaccharide, 12 kg of casein, 10 kg of isomaltooligosaccharide, 34.8 L of water; 2 kg of mono- and diglycerol fatty acid esters; 4 kg of sodium starch octenyl succinate; 0.75 kg of potassium citrate; 0.75 kg of sodium ascorbate; 2 kg of silicon dioxide.

[0152] 1.2 Preparation Method of Compound Fat Powder

[0153] The steps are as follows:

[0154] (1) Pretreatment of oil phase component materials:

[0155] Coconut oil, linseed oil, and safflower oil are respectively fed into a degumming device (hydration tank), heated at 80 °C, 0.3% citric acid is added, and stirred for 15 minutes to hydrolyze the colloidal substances, and then left to stand for sedimentation to remove the colloids, obtaining degummed oil.

[0156] The degummed oil is fed into a deacidification device (caustic refining tank), 0.3% sodium carbonate is added, and stirred for 15 minutes to neutralize the free fatty acids, generating soapstock, and then left to stand for sedimentation to remove the soapstock, obtaining deacidified oil.

[0157] The deacidified oil is fed into a decolorization device (decolorization tank), 1.0% bentonite is added, and stirred for 30 minutes to adsorb the pigments and odor substances in the oil, and then a filtration device is used to filter out the adsorbent, obtaining decolorized oil.

[0158] The decolorized oil is fed into a deodorization device (deodorization tank), and vacuum distillation is carried out at 200 °C with a vacuum degree of 0.3 MPa for 40 minutes to remove the odor substances in the oil, and refined coconut oil, linseed oil and safflower oil are obtained respectively.

[0159] (2) Pretreatment of aqueous phase components

[0160] The resistant dextrin, maltitol oligosaccharide, casein, and isomaltooligosaccharide are respectively placed in a vibrating screen. The screen aperture is adjusted to 80 mesh, the vibration frequency is 100 Hz, and the amplitude is 5 mm for sieving to remove large particles and impurities, and the treated resistant dextrin, maltitol oligosaccharide, casein, and isomaltooligosaccharide are obtained.

[0161] The potassium citrate, mono- and diglycerol fatty acid esters, sodium octenyl succinate starch, sodium ascorbate, and silicon dioxide are respectively placed in a rotary vibrating screen. The screen aperture is adjusted to 120 mesh, and the rotation speed is 2000 rpm for sieving to ensure that the particles are fine and uniform, and the treated potassium citrate, mono- and diglycerol fatty acid esters, sodium octenyl succinate starch, sodium ascorbate, and silicon dioxide are obtained, which is convenient for subsequent mixing and dispersion.

[0162] (3) Microencapsulation

[0163] Preparation of oil phase: Mix 18 kg of refined coconut oil, 12 kg of linseed oil and 12 kg of safflower oil. Heat it to 60 °C in a stirring tank and stir evenly at a speed of 800 rpm with a high-speed shear stirrer for 15 minutes.

[0164] Preparation of aqueous phase: Mix 22 kg of treated resistant dextrin, 14 kg of maltitol oligosaccharide, 12 kg of casein and 10 kg of isomaltooligosaccharide, add 34.8 L of water, heat it to 70 °C in a stirring tank, and stir at a speed of 1500 rpm with a high-speed shear stirrer for 45 minutes until completely dissolved.

[0165] Primary emulsification: Slowly add the oil phase to the aqueous phase in a high-shear emulsifier, carry out high-speed shear emulsification at 60 °C with a shear speed of 12000 rpm for 15 minutes to form a primary emulsion.

[0166] Homogenization: Feed the primary emulsion into a homogenizing emulsifier for high-pressure homogenization. The homogenization pressure is 50 MPa and the number of homogenization times is 5 times to ensure the stability of the emulsion and form a uniform microcapsule emulsion.

[0167] Add emulsifier and wall material: In a stirring tank, mix the microcapsule emulsion with 2 kg of mono- and diglycerol fatty acid esters and 4 kg of sodium starch octenyl succinate, and stir using a high-speed shear stirrer at a speed of 800 rpm for 15 minutes to further improve the stability of the emulsion and the microencapsulation effect, obtaining a microencapsulated emulsion.

[0168] (4) Spray drying of the microencapsulated emulsion

[0169] Feed the microcapsule emulsion into a spray drying tower, atomize the emulsion into uniform and fine droplets through a centrifugal atomizer, control the inlet air temperature at 180 °C, the outlet air temperature at 90 °C, and the atomization pressure at 30 MPa, so that the water in the emulsion evaporates rapidly, forming microcapsule powder.

[0170] Use a cyclone separator to collect the dried microcapsule powder to improve the product yield and purity.

[0171] For the microcapsule powder that cannot be completely collected, use a bag filter for further collection to ensure the purity of the product.

[0172] (5) Mixing

[0173] According to the production scale and product characteristics, select a conical mixer, mix the microcapsule powder obtained by spray drying with 0.75 kg of potassium citrate, 0.75 kg of sodium ascorbate, and 2 kg of silicon dioxide in the mixer, control the mixing speed at 800 rpm, and the mixing time at 30 minutes to ensure that each component is fully and evenly mixed, ensuring the uniform distribution of potassium citrate, sodium ascorbate, and silicon dioxide in the microcapsule powder. The product obtained after uniform mixing is the final compound fat powder.

[0174] Example 4

[0175] 2. Structural characterization of the compound fat powder

[0176] 2.1 Determination of the particle size and Zeta potential of the compound fat powder

[0177] Take an appropriate amount of the compound fat powder (compound fat powder, CFP) prepared in Example 1 and prepare a solution with a concentration of 0.1 mg / mL using ethanol, and use a laser nano-particle size analyzer (Litesizer 500) to detect its particle size distribution and Zeta potential. Each sample is measured 3 times repeatedly.

[0178] The measurement results of the particle size and Zeta potential of the compound fat powder are as Figure 1 shown. According to Figure 1As shown in A of , the measured particle sizes of the composite fat powder were 582.19 nm, 499.77 nm, and 582.56 nm respectively, and the PDI (Polymer Dispersity Index) values were 0.2067, 0.2094, and 0.1215 respectively. Since the PDI was less than 0.3, it indicated that the particle size distribution of this system was uniform, with good stability and dispersibility. Zeta potential is one of the indicators used to evaluate the stability of nanoparticles. Nanoparticles with higher Zeta potential values are relatively more stable. As Figure 1 shown in B of , the Zeta potential values of the composite fat powder after detection were -15.87 mV, -15.80 mV, and -14.28 mV respectively. The Zeta potential data results indicated that the sample particles might undergo a certain degree of aggregation, but it was not easy for them to attract each other and aggregate in large quantities, and the particle stability of the microcapsule powder was relatively good.

[0179] 2.2 Scanning Electron Microscopy Analysis

[0180] Fix the CFP sample powder on the sample copper stage, gently blow off the excess powder, and after sputtering with gold, use a scanning electron microscope (SEM) to observe the microscopic morphological characteristics of CFP, with the acceleration voltage set at 5 kV.

[0181] Morphological analysis of the composite fat powder was carried out by SEM, as Figure 2 shown. Figure 2 A, B, and C in respectively represent the scanning electron microscope images of CFP at different magnifications. As can be seen from Figure 2 , the shape of CFP is a regular spherical structure without holes, the surface structure is smooth and complete without cracks, and there are only slight depressions, which may be formed during the shrinkage of the composite fat powder during the cooling process after atomization.

[0182] 2.3 TGA Thermogravimetric Analysis

[0183] Precisely weigh 4.4690 mg of the composite fat powder with a balance, put it into an alumina crucible, place it in the instrument sample chamber, adjust the baseline, set the temperature range to 30 - 600 °C, the gas flow rate to 50 mL / min, the experimental gas to nitrogen, and use a thermogravimetric analyzer (Netzsch TGA209F3, Germany) to conduct thermogravimetric analysis on the composite fat powder at a heating rate of 10 K / min.

[0184] The thermogravimetric analysis results of CFP are shown in Figure 3 . As can be seen from Figure 3It can be seen that the TGA heating range is 30 - 600 °C. As the temperature increases, the sample mass gradually decreases. The TGA curve of CFP can be divided into three stages: The first stage is from 30 - 180 °C, where the weight loss curve is flat and the weight loss rate of the sample is 2.5663%. The second stage is from 180 - 420 °C, with a weight loss rate of 85.3675%, and it starts to change rapidly around 300 °C, indicating that the sample begins to thermally decompose. Finally, in the temperature range of 420 - 600 °C, the curve tends to be stable, and the thermal decomposition of the compound fat powder is basically completed, and the weight change gradually stabilizes.

[0185] 2.4 Fourier Transform Infrared Spectroscopy (FT-IR)

[0186] Referring to the method of Wei Mengling (Wei Mengling et al. Identification of Forsythia suspensa from different producing areas by Fourier transform infrared spectroscopy combined with chemometrics [J]. 2023, Acta Chinese Medicine and Pharmacology, 51: 42 - 49), an appropriate amount of compound fat powder was measured using a Fourier transform infrared spectrometer, and the scanning spectral range was set to 500 - 4000 cm -1 , with a resolution of 4.000 and 32 scans, and the infrared absorption spectrum of the compound fat powder was collected.

[0187] The Fourier transform infrared spectroscopy measurement results of the compound fat powder are as Figure 4 shown. It can be seen from Figure 4 that CFP has a very strong and broad characteristic peak at 3383.53 cm -1 , which is the stretching vibration of the characteristic peak caused by -OH. The peak at 2923.56 cm -1 is related to the asymmetric stretching of the C-H bond, that is, the stretching of the free amino acid NH3 band. The absorption peak at 2854.11 cm -1 is the stretching vibration caused by C-H. The absorption peaks at 1743.88 cm -1 and 1657.35 cm -1 are the stretching vibrations of the characteristic peaks caused by C=O. The absorption peak at 1464.79 cm -1 is the in-plane bending vibration absorption peak of C-H. The absorption peak at 1380.06 cm -1 is the deformation vibration of C-O, and 1234.43 cm -1 is the CH2 bending vibration. At the same time, at 1173.77 cm -1 it is caused by the in-plane bending vibration of C-H, 1103.67 cm -1 is the C-O-H stretching vibration, and 723.78 cm -1 is the C-C stretching vibration.

[0188] 2.5 X-ray Diffraction Determination (XRD)

[0189] The CFP was tested using an X-ray diffractometer (Rigaku Ultima IV, Japan). The test conditions were Cu-Kα radiation, tube voltage of 40 kV, tube current of 40 mA, step size of 0.02°, scanning range of 5° to 90°, and the diffraction spectrum of the sample was recorded.

[0190] XRD can be used to characterize the crystal, amorphous structure, lattice parameters and other structural features of samples, and has the advantages of simple sample preparation and non-destructiveness to samples. The XRD results of the composite fat powder are as Figure 5 shown. A broad peak was observed at around 2θ = 20°, indicating that CFP mainly exists in the form of an amorphous polymer.

[0191] 3. Network pharmacology analysis of composite fat powder against obesity

[0192] 3.1 Screening of targets of composite fat powder

[0193] The chemical components of CFP were obtained by literature collection and collation, and the SMILES numbers of each component were obtained using the PubChem database. Then they were imported into the Swiss Target Prediction database, and the attribute was set to "Homosapiens" to obtain the potential action targets of the chemical components of CFP. And the PharmMapper database was used to supplement the component targets.

[0194] Prediction of candidate targets related to composite fat powder and obesity

[0195] Based on literature retrieval, a total of 290 chemical components were obtained from CFP. After database search, it was found that the targets related to 48 chemical components could not be predicted. Finally, a total of 13,139 action targets were predicted from 242 chemical components of CFP. In addition, a total of 2,474 disease targets related to obesity were retrieved through the Gene Cards and OMIM databases. Finally, the compound targets and disease targets were respectively imported into the jveen network platform, and 366 common genes of CFP and obesity were obtained. The results are as Figure 6 shown.

[0196] 3.2 Obtaining disease targets of obesity

[0197] Using "obesity" as the keyword, disease-related targets were obtained from the OMIM and GeneCards databases, and the results were integrated and analyzed to delete duplicate targets and obtain obesity-related targets.

[0198] 3.3 Analysis of intersection targets of composite fat powder and obesity

[0199] Intersect the target genes of the CFP active ingredient and the obesity target genes, and use the Microbial Information platform to create a Venn diagram to obtain the intersection targets, which are the common targets of the drug and the disease.

[0200] 3.4 Construction of the "Ingredient-Target" Network

[0201] Cytoscape is a software for visual exploration of biomedical networks composed of protein, gene, and other types of interactions. In this invention, Cytoscape 3.7.2 software is used to construct the network between the effective ingredients of CFP and the related targets, and topological analysis of the network is carried out.

[0202] The "Ingredient-Target" network is as Figure 7 shown. This network has a total of 1204 nodes and 12132 edges. Among them, diamonds represent the chemical components of CFP, circles represent the action targets, and each edge represents the connection and interaction between the active ingredient and the target. It can be found from the network diagram that multiple targets correspond to the same active ingredient, and one target can also correspond to different active ingredients, indicating that CFP may play a role by intervening multiple targets through multiple components. The degree value of the node can measure the importance of the active ingredient and the target. By calculating the degree value of the nodes in the network, the chemical components with higher degree values mainly include: catechin, erucic acid, C17:0 heptadecanoic acid, linoleic acid, C17:1 heptadecenoic acid, stearic acid, etc.

[0203] 3.5 Construction and Analysis of Protein-Protein (PPI) Interaction Network

[0204] To better illustrate the interaction relationship between the drug targets and the disease targets and the mining of the core action targets. The common targets are imported into the STRING database, the species is limited to "Homo sapiens", and the "minimum required interaction" is set to "highest confidence (0.7)". The downloaded TSV format result file is imported into Cytoscape 3.7.2 software to construct a protein interaction network and perform topological analysis.

[0205] After submitting 366 intersection targets to the STRING 12.0 database to obtain protein interaction information, and then importing it into Cytoscape 3.7.2 software, a PPI network is obtained. This network consists of 344 nodes and 2307 edges. The PPI network is as Figure 8As shown, the nodes represent the targets, the size of the nodes represents the degree value, and each edge represents the protein-protein interaction relationship. The connections between the various targets shown in the network diagram indicate that the mechanism of action of the drug in treating diseases is complex and diverse, and it may be the synergistic effect of multiple targets. Cluster analysis was performed using the MCODE function in Cytoscape 3.7.2 software. According to the average Score value ≥ 4.7, a total of 3 cluster networks were obtained. Among them, the red cluster network has the highest score, with a Score value of 15.189; the Score value of the cluster network composed of blue nodes is 8.250, and the Score value of the cluster network composed of orange nodes is 5.000, suggesting that the red node network may be the clustering of key targets.

[0206] 3.6 Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway Enrichment Analysis

[0207] To clarify the role of the action targets of each active ingredient in the signaling pathway and to clarify the mechanism of action of the drug, gene ontology (GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed on the 366 intersection targets screened using the Metascape 3.5 online data platform. The PValue was set to 0.01, and the obtained results were visually analyzed using the Weishengxin platform.

[0208] To further clarify the mechanism of action of CFP in obesity, the 366 intersection targets were input into the Metascape 3.5 online platform for GO and KEGG pathway enrichment analysis, and a total of 3304 GO terms were obtained, including 357 in molecular function (MF), 134 in cellular component (CC), and 2813 in biological process (BP). The top 20 terms with the highest enrichment in the BP, MF, and CC categories were selected, and the results are shown in Figure 9 A, that is, the results of the biological process analysis showed that the targets of CFP in treating obesity were mainly related to the response to hormones, the response to exogenous stimuli, membrane rafts, dendrites, phosphatidylinositol 3-kinase, oxidoreductase activity, etc.

[0209] To more intuitively predict the pathway involved in the target, the pathway information related to the target was obtained from the KEGG analysis, and the results are as follows Figure 9As shown in Figure B, it can be found from the figure that the key targets are closely related to various metabolic diseases, and these targets may affect lipid metabolism, signal transduction, transport and catabolism in the body, and act on the endocrine system, further participating in the development of cancer and endocrine metabolic diseases. A total of 238 signaling pathways (P<0.05) were obtained through KEGG pathway enrichment analysis. The key targets are mainly related to pathways such as the insulin signaling pathway, neuroactive ligand-receptor interaction signaling pathway, cAMP signaling pathway, and insulin resistance. Based on the core targets and pathway enrichment results, the insulin resistance signaling pathway was mainly explored. Figure 9 Figure D shows that CFP may treat obesity through the insulin resistance pathway. The results of network pharmacology analysis indicate that CFP may exert anti-obesity effects through multiple pathways, among which the insulin resistance pathway may play a key role.

[0210] 3.7 Construction of the "key component-potential target-core pathway" network diagram

[0211] The chemical components of the drug and their action targets were imported into the Cytoscape 3.7.2 software to construct a "component-target" network; and the "component-target" network was merged with the PPI network using the Merge tool in the Cytoscape 3.7.2 software to obtain the "component-target-disease" core network. At the same time, the top 20 key signaling pathways in the KEGG enrichment results were mapped onto the "component-target-disease" network, and finally the "key component-potential target-core pathway" network was obtained.

[0212] Degree value is generally considered to be a key indicator representing the importance of nodes. The network diagram of the "key component-potential target-core pathway" is as Figure 10 shown. There are 1,226 nodes and 15,989 edges in this network. According to the screening condition that the degree value is greater than the median, there are 23 chemical components with a degree value higher than the median. The top-ranked components are catechin, erucic acid, C17:0 heptadecanoic acid, linoleic acid, 13-octadecenoic acid, 5-amino-2,4-dimethylbenzoic acid, etc. The above components may play an important role in the treatment of obesity by CFP. The top-ranked core targets are CA2, AR, EGFR, CA1, HSD11B1, PTPN1, SRC, etc., and the core targets are mainly enriched in the insulin signaling pathway, insulin resistance, calcium signaling pathway, and serotonergic synapse signaling pathway. It can be seen from the network diagram that multiple targets can correspond to the same component, and one component can correspond to multiple targets. The targets of drug action are distributed on multiple signaling pathways, which also proves that CFP may exert therapeutic effects on obesity through the coordination of multiple components, multiple targets, and multiple pathways.

[0213] 3.8 Molecular docking

[0214] Molecular docking is a theoretical simulation method for drug design based on the characteristics of the receptor and the interaction mode between the receptor and the drug molecule. It mainly studies the interactions between molecules (such as ligands and receptors) and predicts their binding modes and affinities. According to the above network analysis results, the target structure was obtained using the PDB database, and the core targets and CFP chemical components were subjected to molecular docking using AutodockVina software to evaluate the binding ability of the components to the core targets based on the magnitude of the binding energy. Finally, Pymol was used to visually analyze the molecular docking results.

[0215] The top ten proteins and chemical components ranked by the Degree value were selected for molecular docking, and the results are as Figure 11 shown in Figure A. Molecular docking was performed on 10 compounds and 10 core targets, obtaining 100 sets of ligand-receptor docking results. The receptors with good affinity for the ligand were screened according to the molecular docking binding energy. The smaller the molecular docking binding energy, the better the docking effect, and when the binding energy ≤ -5 kcal / mol, it indicates good affinity between the ligand and the receptor. Among them, the binding energies of Catechin with IL6, TNF, and STAT3 were -6.3, -6.0, and -6.9 kcal / mol respectively, and these 3 core targets were the core targets enriched in the insulin resistance pathway. The molecular docking results are shown in the form of a heat map, as Figure 11 shown in Figure B, and the molecular docking binding energy is negatively correlated with the affinity between the receptor and the ligand.

[0216] 4. Weight loss effect of compound fat powder on high-fat diet-induced obese rats

[0217] 4.1 Experimental animals

[0218] 90 six-week-old male SD rats were purchased from Beijing Spey Foster Biotechnology Co., Ltd., license number: SYXK(Qing)2022-0001. All animals were housed in an SPF laboratory at a temperature of 22 ± 1 °C, a relative humidity of 60% - 70%, a 12-hour light and dark cycle, and had free access to water. The animal experiments in this study have been approved by the Experimental Animal Ethics Committee of the Northwest Institute of Plateau Biology, Chinese Academy of Sciences (batch number: NWIPB20171106-01).

[0219] 4.2 Establishment of a rat obesity model

[0220] After one week of adaptive feeding, 90 rats were randomly divided into two groups: a normal diet group (ND, n = 10) fed with normal feed, and a model group (HFD, n = 80) fed with a high-fat diet D12492 (containing 34.9% fat, 26.3% carbohydrates, and 26.2% protein, purchased from Shanghai Bio-Pack Biotechnology Co., Ltd.). Body weight and body length were measured once a week, and the daily food intake and remaining food amount were recorded. When the average body weight of the model group was more than 20% greater than that of the normal group, the model was considered successfully established.

[0221] 4.3 Grouping and drug administration

[0222] After 2 weeks of feeding, the successfully induced obese rats were randomly divided into 5 groups, namely the model group (HFD, n = 10), the semaglutide group (SEMA, n = 10), the low-dose compound fat powder group (L-CFP, n = 10), the medium-dose compound fat powder group (M-CFP, n = 10), and the high-dose compound fat powder group (H-CFP, n = 10). Body weight and body length were measured once a week, and the daily food intake and remaining food amount were recorded. Both the model group and the drug administration groups were fed with a high-fat diet and gavaged with the test samples once a day for 6 consecutive weeks.

[0223] The drug administration doses in this experiment were determined based on the conversion relationship between the equivalent drug doses for experimental animals and humans in pharmacological experiments. Six times the daily intake (6 g) of an adult (60 kg) was the equivalent dose (0.1 g / kg). The L-CFP (0.6 g / kg), M-CFP (1.2 g / kg), and H-CFP (2.4 g / kg) were respectively 1, 2, and 4 times the equivalent dose. The administration dose of the positive drug SEMA was set at 0.0007 g / kg, and the ND group and the HFD group were given the same volume of distilled water.

[0224] 4.4 Sample collection

[0225] After drug intervention, the rats were weighed and euthanized after cardiac blood collection. The liver, kidneys, and perirenal adipose tissue were excised and weighed, and the organ coefficients of the liver and kidneys and the obesity index were calculated. The body length was measured and the Lee's index was calculated.

[0226] 4.5 Biochemical indexes

[0227] Blood was collected from the hearts of rats and serum was separated. The changes in the contents of relevant biochemical indicators in serum were measured respectively: the contents of total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C); blood glucose and insulin levels: the contents of glucose (GLU) and insulin (INS); liver function-related indicators: alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH); bile function-related indicators: total protein (TP), albumin (ALB) and total bile acid (TBA); kidney function-related indicators: creatinine (CREA), uric acid (UA) and urea (UREA); obesity-related indicators: the contents of leptin (LEP), lipoprotein lipase (LPL) and hepatic lipase (HL), etc. The remaining serum was aliquoted and stored at -80 °C for future testing.

[0228] 4.6 Histopathological examination

[0229] Take some liver and perirenal fat and fix them in 10% paraformaldehyde for more than 24 h. Embed the tissues in paraffin and cut them into 3-μm thick sections. After a series of processes such as dehydration and paraffin embedding of the sections, hematoxylin-eosin (HE) staining was performed, and histopathological changes were observed under a microscope.

[0230] 4.7 Statistical analysis

[0231] All statistical analyses were performed using GraphPad Prism 8.3.0 software, and all were expressed as mean ± S.E.M. One-way ANOVA and Dunnett's multiple comparison test were used for comparison among multiple groups. P < 0.05 was considered to be significantly different.

[0232] 5. Experimental results:

[0233] 5.1 Effects of CFP on body weight, liver and adipose tissue weights and morphology in rats

[0234] The results of the effects of CFP on body weight, liver and adipose tissue weights are as Figure 12 shown. By measuring body weight weekly, it was found that a high-fat diet led to an increase in the body weight of mice, while the interventions of L-CFP, M-CFP and H-CFP significantly reduced the increase in body weight ( Figure 12 -A). Figure 12 -B shows that the Lee's index of the intervention group was significantly decreased (P < 0.05). And Figure 12-C indicates that the food intake of the HFD group is lower than that of the ND group, but there is no significant difference. Compared with the HFD group, the food intake of rats in the CFP intervention group decreased significantly (P<0.01). In addition, HFD induced significant expansion of adipose tissue in rats, and the epididymal fat coefficient (P<0.01), perirenal fat coefficient (P<0.01), body fat rate (P<0.01) and liver weight (P<0.01) increased significantly. After CFP treatment, the weight of adipose tissue decreased significantly.

[0235] 5.2 Effects of CFP on blood lipid and blood glucose levels in rats

[0236] Obesity is considered a disease caused by multiple inducing factors and is often accompanied by abnormal glucose and lipid metabolism. Figure 13 Shown are the changes in the content of relevant blood lipid indicators in the serum of rats. As Figure 13 shown in A and B, the contents of TC and TG in the HFD group were the highest, significantly higher than those in the CFP group. Compared with the HFD group, the contents of TC and TG in the SEMA group, L-CFP group, M-CFP group and H-CFP group decreased significantly (P<0.01). Figure 13 The results in C and D suggest that the contents of LDL-C and HDL-C in the HFD group increased, while the contents of LDL-C and HDL-C in each drug administration group decreased to varying degrees. At the same time, the drug administration group also reduced the level of glucose content (P<0.01 or P<0.05), as shown in 13-D.

[0237] 5.3 Effects of CFP on indicators related to liver function in rats

[0238] The results of indicators related to liver function are as Figure 14 shown. Compared with ND, the levels of serum ALT, AST and LDH in rats in the HFD group increased significantly (P<0.01 or P<0.05). Compared with the HFD group, the low, medium and high dose groups of CFP could significantly reduce the expression of ALT, AST and LDH, and the high dose had the most obvious effect, with statistically significant differences (P<0.01).

[0239] 5.4 Effects of CFP on indicators related to gallbladder function in rats

[0240] The results of indicators related to gallbladder function are as Figure 15 shown. Compared with ND, TP and ALB in rats in the HFD group increased significantly, with statistical differences (P<0.05 or P<0.01), while there was no statistical difference in the level of TBA. Compared with the HFD group, the M-CFP dose group could significantly reduce the expression of ALB, and there was no statistical difference in the low and high dose groups. In addition, the CFP intervention groups with different doses could reduce the expression of TBA and TP (P<0.05 or P<0.01).

[0241] 5.5 Effects of CFP on the levels of indicators related to lipid metabolism in rats

[0242] By detecting the changes in the contents of lipid metabolism-related indicators in rat serum, the results are as Figure 16 shown. Compared with the ND group, the LEP level in the serum of rats in the HFD group increased. Compared with the HFD group, the CFP group and the SEMA group could significantly reduce the LEP level, and there was no significant difference in the reduction of the LEP level by L-CFP (P>0.05). In addition, compared with the ND group, the LPL level in the serum of rats in the HFD group decreased, and there was no significant difference in the HL group (P>0.05). Compared with the HFD group, the CFP intervention group could increase the expression of LPL and HL, and there was no significant difference in the reduction of LPL by the SEMA group and the H-CFP group (P>0.05).

[0243] 5.6 Effects of CFP on renal function and insulin-related indicator levels in rats

[0244] As Figure 17 shown. Compared with the ND group, the serum UA of rats in the HFD group increased significantly (P<0.05), while there was no significant difference in CER. The L-CFP intervention group could reduce the CRE expression and there was a significant difference in UA (P<0.05), while there was no significant difference in the H-CFP and M-CFP groups. Insulin is secreted by pancreatic islet β cells and is a hormone that specifically regulates blood glucose changes in the body and plays an important role in the body's carbohydrate and lipid metabolism. By detecting the changes in insulin content in rat serum. Compared with the ND group, the INS content in the serum of rats in the HFD group increased (P<0.05). Compared with the HFD group, the INS content in the SEMA, M-CFP and H-CFP groups all decreased (P<0.05 or P<0.01), and there was no significant difference in the L-CFP group (P>0.05).

[0245] 5.7 Results of HE staining of rat liver tissue

[0246] The results of HE staining of the liver are as Figure 18 shown. In the ND group, the capsule of the liver tissue was intact, the lobulation of the liver lobules was not obvious, and the hepatic cords were arranged relatively neatly; the endothelium of the central vein was intact, and the hepatocytes were arranged radially around the central vein; compared with the ND group, slight fatty degeneration of hepatocytes was visible in the liver tissue of the HFD group, and there were round lipid droplets of different sizes and non-staining in the cytoplasm of hepatocytes. Locally, many small lipid droplets ruptured and fused into large lipid droplets, and the cell nucleus was mostly deviated to one side of the cell; compared with the HFD group, the hepatic sinusoid structure was normal in the drug administration group, and the structures of the interlobular artery, interlobular vein and interlobular bile duct in the portal area were relatively complete, and no obvious fibrous tissue hyperplasia and inflammatory cell infiltration were seen around. There was no obvious improvement in the overall lesion degree in the positive drug group and the low-dose group, and the overall lesion degree in the medium-dose group and the high-dose group was slightly reduced.

[0247] 5.8 Results of HE staining of rat adipose tissue

[0248] The results of fat HE staining were as follows Figure 19 shown. In the ND group, the overall contour of adipocytes was smaller and the number was larger. In the HFD group, single-vesicle adipocytes aggregated, and large lipid droplets could be seen in white adipocytes, squeezing the cytoplasm and nucleus to the cell edge, forming a "ring"-like cytoplasm and a "semicircular"-shaped nucleus, with loose arrangement. Compared with the HFD group, there was no obvious improvement in the positive drug group, low-dose group, and medium-dose group as a whole. The degree of overall lesion in the high-dose group was slightly reduced, and a certain degree of shrinkage of adipocytes was seen.

[0249] Although the above embodiments have described the present invention in detail, they are only a part of the embodiments of the present invention, rather than all embodiments. People can also obtain other embodiments based on these embodiments without creative efforts, and these embodiments all fall within the protection scope of the present invention.

Claims

1. Application of a compound fat powder in the preparation of a product for treating or improving obesity, characterized in that: The composite fat powder comprises coconut oil, linseed oil and safflower seed oil, and the mass ratio of the coconut oil, linseed oil and safflower seed oil is (12-18):(8-12):(6-12).

2. The use according to claim 1, characterized in that: The composite fat powder comprises coconut oil, linseed oil, safflower oil, resistant dextrin, maltooligosaccharide, casein, isomaltose, mono- and di-glycerol fatty acid esters, sodium octenyl succinate starch, potassium citrate, sodium ascorbate and silicon dioxide. The mass ratios of the coconut oil, linseed oil, safflower oil, resistant dextrin, maltooligosaccharide, casein, isomaltose, mono- and di-glycerol fatty acid esters, sodium octenyl succinate starch, potassium citrate, sodium ascorbate and silicon dioxide are (12-18):(8-12):(6-12):(15-22):(8-14):(8-12):(6-10):(1-2):(2-4):(0.25-0.75):(0.25-0.75):(1-2).

3. The use according to claim 1 or 2, characterized in that: The preparation method of the composite fat powder comprises the following steps: (1) preparing the oil phase: mixing the coconut oil, linseed oil and safflower oil by heating and stirring; (2) Preparation of aqueous phase: adding resistant dextrin, maltooligosaccharide, casein and isomaltooligosaccharide into water, heating and stirring to mix; (3) Primary emulsification: In a high shear emulsifier, slowly add the oil phase to the water phase for shear emulsification to obtain a preliminary emulsion; (4) Homogenization: homogenize the primary emulsion 3 to 5 times to obtain a microcapsule emulsion; (5) adding emulsifier and wall material: mixing the microcapsule emulsion with mono- and di-glycerol fatty acid esters and sodium starch octenyl succinate by shearing and stirring to obtain the embedded microcapsule emulsion; (6) Spray drying: The embedded microcapsule emulsion is spray dried to obtain microcapsule powder; (7) Mixing: The microcapsule powder obtained by spray drying is mixed with potassium citrate, sodium ascorbate and silicon dioxide to obtain the composite fat powder.

4. The use according to any one of claims 1 to 3, characterized in that: The compound fat powder can reduce body weight, the obesity includes obesity caused by a high-fat diet, and the product includes a medicine.

5. Use of the compound fat powder according to any one of claims 1 to 3 in preparing a product for reducing liver weight and / or adipose tissue weight.

6. Use of the compound fat powder according to any one of claims 1 to 3 in preparing a product for treating or improving abnormal blood lipid levels caused by obesity and / or treating or improving abnormal blood sugar levels caused by obesity.

7. Use of the compound fat powder according to any one of claims 1 to 3 in preparing a product for treating or improving abnormal liver function caused by obesity.

8. Use of the compound fat powder according to any one of claims 1 to 3 in the preparation of a product for treating or improving abnormal bile function caused by obesity.

9. Use of the compound fat powder according to any one of claims 1 to 3 in preparing a product for treating or improving abnormal lipid metabolism caused by obesity.

10. Use of the compound fat powder according to any one of claims 1 to 3 in preparing a product for treating or improving abnormal insulin secretion caused by obesity and / or a product for treating or improving abnormal renal function caused by obesity.

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