CN114731985A

CN114731985A - Construction method of metabolism-related fatty liver disease non-human primate model

Info

Publication number: CN114731985A
Application number: CN202210320753.5A
Authority: CN
Inventors: 任娇艳; 徐真真; 刘炜
Original assignee: South China University of Technology SCUT
Current assignee: South China University of Technology SCUT
Priority date: 2022-03-29
Filing date: 2022-03-29
Publication date: 2022-07-12
Anticipated expiration: 2042-03-29
Also published as: CN114731985B

Abstract

The invention discloses a construction method of a non-human primate model with metabolic-related fatty liver disease, belonging to the technical field of experimental animals. The construction method of the invention relates to: by taking a non-human primate, namely a cynomolgus monkey, as a model animal and feeding a high-fat, high-sugar and high-cholesterol feed, the weight of the animal is increased along with the feeding time, and the glucose, cholesterol and triglyceride levels in blood are obviously increased to cause the phenomenon of glycolipid metabolism disorder, so that the accumulation of liver fat and the fibrosis are caused. The constructed non-human primate model of the metabolism-related fatty liver disease can simulate the occurrence and development of human metabolism-related fatty liver caused by improper diet in physiological and pathological processes, and provides a preclinical assessment tool for developing research and development of nutrients and medicines in related fields.

Description

Construction method of metabolism-related fatty liver disease non-human primate model

Technical Field

The invention belongs to the technical field of experimental animals, and particularly relates to a construction method of a non-human primate model with metabolic-related fatty liver disease.

Background

The Metabolic Associated Fatty Liver Disease (MAFLD) is known as nonalcoholic fatty liver disease (NAFLD), the global morbidity is as high as 25%, the health of human beings is seriously harmed, and huge economic burden is caused to the society. Unhealthy living habits such as sedentary and short-time movement, unhealthy eating habits such as high dietary calorie and unreasonable dietary structure are closely related to the continuously increased incidence of the MAFLD. The MAFLD is the second chronic liver disease of viral hepatitis, but the pathogenesis of the MAFLD is not completely clarified, and the MAFLD lacks effective measures in treatment.

The animal model has important functions in the fields of exploring pathogenesis of diseases, evaluating diagnosis methods, screening prevention and treatment medicines and the like. At present, the model for researching the MAFLD disease at home and abroad is mainly a NAFLD model construction method, and the related methods mainly comprise three types: 1) gene knockout or gene mutation models; 2) nutritional, drug or toxicant-induced models; 3) the composite model is mainly the combined application of a gene model and a nutrition model. The ob/ob mouse is the most widely used gene warping model at present, and its ob gene (leptin-encoding gene) is spontaneously mutated to cause leptin synthesis disorder, manifested as obesity, hyperinsulinemia, hyperlipidemia, diabetes, fatty liver, etc., and although having characteristics consistent with those of human NAFLD, cannot spontaneously become NASH (nonalcoholic steatohepatitis). The most widely used nutrition-induced models, including MCD diet model (methionine deficiency), HFD diet model (high fat diet) and high carbohydrate diet, were modeled primarily for rodents. The model construction method is simple, but because the severity of diet-related diseases is different among animals of different species, strains, sexes and genetic backgrounds, the model cannot completely cover the disease spectrum and pathogenesis of human MAFLD.

Based on the above, establishing an animal model which is similar to human pathological changes, has a complete disease spectrum, is stable and reliable, and can better simulate the general metabolic disorder background of the human MAFLD becomes a problem to be solved urgently. The non-human primate is very similar to human life habit, genetic background, especially organism immunity, and is the best model animal for researching clinical diseases. Chinese patent discloses a non-alcoholic chronic steatohepatitis non-human primate model and a construction method and application thereof, but the adopted construction method comprises high fat diet, CCL4 chemical induction and alcohol drinking, and certain difference exists between the model and the induction factors of human metabolism-related fatty liver disease.

Disclosure of Invention

In order to overcome the problems in the prior art, the invention aims to provide a construction method of a non-human primate model for metabolic-related fatty liver disease.

The purpose of the invention is realized by at least one of the following technical solutions.

The invention provides a construction method of a non-human primate animal model with metabolic-related fatty liver disease, which comprises the steps of feeding a non-human primate with a high-fat high-sugar high-cholesterol feed to enable the animal to generate glycolipid metabolic disturbance and further induce liver to generate adiposis and fibrosis, wherein the high-fat high-sugar high-cholesterol feed comprises, by mass, 17-25 wt% of crude protein, 30-45 wt% of crude fat, 13-17 wt% of crude fiber, 3-15 wt% of fructose, 1-3 wt% of cholesterol, 1-4 wt% of calcium, 0.7-1 wt% of phosphorus, 0.2-0.7 wt% of vitamin and 0.3-5 wt% of mineral substances.

Further, in the construction method, the non-human primate is a cynomolgus monkey bred in a single cage at the age of 5 to 25 years.

Further, in the construction method, the non-human primate is a cynomolgus monkey bred in a single cage at the age of 5 to 23 years.

Further, in the construction method, the non-human primate is a cynomolgus monkey, the age range is 5-20 years, and the breeding mode is single-cage breeding.

Further, in the construction method, enough high-fat high-sugar high-cholesterol feed is supplied, the supply of the high-fat high-sugar high-cholesterol feed to the cynomolgus monkeys is unlimited, and animals freely eat the feed for 3 to 12 months.

Furthermore, in the construction method, the main nutritional raw materials of the high-fat, high-sugar and high-cholesterol feed comprise more than one of soybean meal, fish meal and chicken powder to provide protein; providing fat with more than one of corn oil, sunflower seed oil and lard oil; providing carbohydrate by more than one of corn starch, flour and rice flour; one or more of bran and rice bran provide crude fiber.

Further, in the construction method, the nutritional ingredients of the high-fat high-sugar high-cholesterol feed comprise 2-3 wt% of cholesterol by mass percentage.

Further, in the construction method, the calorie composition of the high-fat, high-sugar and high-cholesterol feed comprises the following steps: 680-1011 Kcal/kg of protein, 2700-4050 Kcal/kg of fat, 960-1160 Kcal/kg of carbohydrate, and 4660-5850 Kcal/kg of total calories.

Further, in the construction method, the calorie composition of the high-fat, high-sugar and high-cholesterol feed comprises the following steps: 960-1120 Kcal/kg carbohydrate.

Further, in the construction method, the fatty acid composition in the high-fat high-sugar high-cholesterol feed is as follows by mass percent: 30-65 wt% of saturated fatty acid, 10-30 wt% of monounsaturated fatty acid and 15-30 wt% of polyunsaturated fatty acid.

Further, in the construction method, the fatty acid composition in the high-fat high-sugar high-cholesterol feed comprises, by mass percent: 51.53-57.85 wt% of saturated fatty acid, 23.78-29.95 wt% of monounsaturated fatty acid and 18.58-28.64 wt% of polyunsaturated fatty acid.

Further, the fatty acid composition in the high-fat high-sugar high-cholesterol feed comprises: 51.85-57.85 wt% of saturated fatty acid.

Further, in the construction method, the ratio of the fatty acid chain length in the high-fat high-sugar high-cholesterol feed comprises the following steps: 6.8 to 27.3 weight percent of medium chain fatty acid (fatty acid with the carbon number of 6 to 12 on the carbon chain) and 72.2 to 93.2 weight percent of long chain fatty acid (fatty acid with the carbon number of more than 12 on the carbon chain).

Furthermore, in the construction method, the model can be formed after the high-fat high-sugar high-cholesterol feed is fed for 3-12 months, the molding rate reaches 72%, the weight of a model animal is obviously increased, and the blood total cholesterol content and the triglyceride content which reflect liver lipid metabolism abnormality are obviously increased; reflecting the magnetic resonance imaging scanning image of liver fat accumulation, wherein the model animal fat accumulation is obvious; biopsies reflecting metabolic disease of the liver show severe steatosis with some degree of fibrotic pathological changes.

Compared with the prior art, the invention has the following advantages and beneficial effects:

1. when the non-human primate animal model of the metabolic-related fatty liver disease provided by the invention is fed to a cynomolgus monkey for 3-12 months, abnormal liver glycolipid metabolism of the model can be found, and liver tissues are subjected to steatosis and fibrosis lesion, so that the disease progression condition of the liver steatosis caused by the abnormal glycolipid metabolism of human beings can be successfully simulated.

2. According to the non-human primate animal model with the metabolic-related fatty liver disease, provided by the invention, the cynomolgus monkey is fed by only a simple feed, a gastric lavage or drug injection means is not required, the animal model with the metabolic-related fatty liver disease can be obtained according to animal ethics, and various symptoms of the human metabolic-related fatty liver disease are simulated, so that a theoretical basis is provided for the research of the human metabolic-related disease, and the animal model has important significance for developing the research and development of nutrients and drugs in related fields.

Drawings

FIG. 1 is a flow chart of the construction of a non-human primate model of metabolic-related fatty liver disease of the present invention.

FIG. 2 is a histogram of the modeling rate of non-human primate model of metabolic fatty liver disease after 12 months of modeling of three groups of high fat, high sugar and high cholesterol diet in examples 1-3.

FIG. 3 is a bar graph of body weight changes in non-human primate model with metabolic fatty liver disease induced by normal diet feed in comparative example 1 and three groups of high fat, high sugar and high cholesterol feeds in examples 1-3 in months 0-12.

FIG. 4 is a bar graph showing the results of serum glucose changes in the non-human primate model with metabolic fatty liver disease induced by the normal diet of comparative example 1 and the three groups of high fat, high sugar and high cholesterol diet of examples 1-3 in 0-12 months.

FIG. 5 is a bar graph showing the results of total serum cholesterol changes in the non-human primate model with metabolic fatty liver disease induced by the normal diet of comparative example 1 and the three groups of high fat, high sugar and high cholesterol diet of examples 1-3 in 0-12 months.

FIG. 6 bar graph of the results of serum triglyceride changes in the non-human primate model of metabolic fatty liver disease induced by the normal diet of comparative example 1 and the three groups of high fat, high sugar and high cholesterol diets of examples 1-3 over 0-12 months.

FIG. 7 is a magnetic resonance imaging scan of liver after 12 months in non-human primate model of induced metabolic fatty liver disease with normal diet of comparative example 1 and three groups of high fat, high sugar and high cholesterol diet of examples 1-3.

FIG. 8 is a graph showing the results of HE staining of liver in non-human primate animal models of metabolic fatty liver disease induced by normal diet feed in comparative example 1 and three groups of high fat, high sugar and high cholesterol feeds in examples 1-3 after 12 months.

FIG. 9 is a graph showing the results of Masson staining of liver after 12 months in non-human primate model with metabolic fatty liver disease induced by normal diet feed in comparative example 1 and three groups of high fat, high sugar and high cholesterol feeds in examples 1-3.

Detailed Description

The following description of the embodiments of the present invention is provided in connection with the accompanying drawings and examples, but the invention is not limited thereto. It is noted that the processes described below, if not specifically described in detail, are all realizable or understandable by those skilled in the art with reference to the prior art. The reagents or apparatus used are not indicated to the manufacturer, and are considered to be conventional products available by commercial purchase.

Example 1

Taking adult cynomolgus monkey as an example, a non-human primate model of metabolic-related fatty liver disease with abnormal glycolipid metabolism and further with hepatic steatosis and fibrotic lesion characteristics is constructed.

In the experiment, firstly, a high-sugar high-cholesterol feed F1 is prepared, wherein the nutritional ingredients of the high-sugar high-cholesterol feed comprise 25 wt% of crude protein, 30 wt% of crude fat, 17 wt% of crude fiber, 3 wt% of fructose, 1 wt% of cholesterol, 4 wt% of calcium, 1 wt% of total phosphorus, 0.7 wt% of vitamins and 5 wt% of minerals; the high-fat, high-sugar and high-cholesterol feed comprises the following components in percentage by weight: protein 1000Kcal/kg, fat 2700Kcal/kg, carbohydrate 960Kcal/kg, total energy 4660 Kcal/kg; the fatty acid composition in the high-fat high-sugar high-cholesterol feed is as follows: 51.58 wt% of saturated fatty acid, 27.78 wt% of monounsaturated fatty acid and 20.64 wt% of polyunsaturated fatty acid, wherein the medium-chain fatty acid accounts for 6.8 wt% and the long-chain fatty acid accounts for 93.2 wt% of the high-fat high-sugar high-cholesterol feed.

25 cynomolgus monkeys of 5-21 years old, weighing 5.25-9.2 kg, are selected for single-cage placement, and are given sufficient high-fat, high-sugar and high-cholesterol feed every day for free food intake and drinking.

Weighing the animals regularly (at 0, 3, 6, 9 and 12 months), and measuring serological changes by collecting blood from four limbs vein for monitoring glucose metabolism and lipid metabolism disorder process; the magnetic resonance imaging scanning and liver biopsy pathological detection are carried out regularly and are used for judging the pathological process of the liver steatosis and the fibrosis.

Example 2

In the experiment, firstly, a high-sugar high-cholesterol feed F2 is prepared, wherein the nutrient components of the high-sugar high-cholesterol feed comprise 22 wt% of crude protein, 35 wt% of crude fat, 14 wt% of crude fiber, 15 wt% of fructose, 2 wt% of cholesterol, 2 wt% of calcium, 1 wt% of total phosphorus, 0.2 wt% of vitamins and 0.5 wt% of minerals; the high-fat, high-sugar and high-cholesterol feed comprises the following components in percentage by weight: protein 880Kcal/kg, fat 3150Kcal/kg, carbohydrate 1160Kcal/kg, total energy 5190 Kcal/kg; the fatty acid in the high-fat high-sugar high-cholesterol feed comprises the following components: 57.58 wt% of saturated fatty acid, 23.78 wt% of monounsaturated fatty acid and 28.64 wt% of polyunsaturated fatty acid, wherein the medium-chain fatty acid accounts for 21.7 wt% and the long-chain fatty acid accounts for 78.3 wt% of the high-fat high-sugar high-cholesterol feed.

25 cynomolgus monkeys of 7-17 years old are selected in the experiment, the weight of the cynomolgus monkeys is 5.4-8.5 kg, the cynomolgus monkeys are placed in a single cage, sufficient high-fat, high-sugar and high-cholesterol feed is given every day, and free food intake and water drinking are achieved.

Example 3

The experiment firstly prepares a high-sugar high-cholesterol feed, namely F3, the nutrient components of which comprise 17 wt% of crude protein, 45 wt% of crude fat, 13 wt% of crude fiber, 15 wt% of fructose, 3 wt% of cholesterol, 4 wt% of calcium, 0.7 wt% of total phosphorus, 0.48 wt% of vitamins and 0.6 wt% of minerals; the high-fat, high-sugar and high-cholesterol feed comprises the following components in percentage by weight: protein 680Kcal/kg, fat 4050Kcal/kg, carbohydrate 1120Kcal/kg, total energy 5850 Kcal/kg; the fatty acid composition in the high-fat high-sugar high-cholesterol feed is as follows: 51.53 wt% of saturated fatty acid, 29.95 wt% of monounsaturated fatty acid and 18.52 wt% of polyunsaturated fatty acid, wherein the medium-chain fatty acid accounts for 27.3 wt% and the long-chain fatty acid accounts for 72.7 wt% of the high-fat high-sugar high-cholesterol feed.

25 cynomolgus monkeys of 6 to 23 years old, weighing 5.0 to 9.5kg, are selected for the experiment, placed in a single cage, and are given enough high-fat, high-sugar and high-cholesterol feed every day for free food intake and water drinking.

Weighing the animals regularly (at 0, 3, 6, 9 and 12 months), and measuring serological changes by collecting blood from four limbs vein for monitoring glucose metabolism and lipid metabolism disorder process; the magnetic resonance imaging scanning and the liver biopsy pathological detection are carried out regularly, and the magnetic resonance imaging scanning and the liver biopsy pathological detection are used for judging the pathological processes of the liver steatosis and the fibrosis.

Comparative example 1

A normal diet feed for cynomolgus monkeys, which is a normal diet feed for cynomolgus monkeys, wherein the nutritional ingredients of the feed comprise 21 wt% of crude protein, 15 wt% of crude fat, 40 wt% of crude fiber, 2 wt% of fructose, 14 wt% of calcium, 10 wt% of total phosphorus, 0.7 wt% of vitamins, and 0.3 wt% of minerals; the calorie of the normal diet feed for the cynomolgus monkeys comprises: protein 840Kcal/kg, fat 1350Kcal/kg, carbohydrate 1680Kcal/kg, total energy 3870 Kcal/kg; the fatty acid components in the normal diet feed for the cynomolgus monkeys are as follows: 31.68 wt% of saturated fatty acid, 21.67 wt% of monounsaturated fatty acid and 46.65 wt% of polyunsaturated fatty acid, wherein the medium-chain fatty acid accounts for 6.7 wt% and the long-chain fatty acid accounts for 93.3 wt% of the normal diet feed for the cynomolgus monkey.

25 cynomolgus monkeys of 7-24 years old are selected, the weight of the cynomolgus monkeys is 5.05-9.7 kg, the cynomolgus monkeys are placed in a single cage, enough normal diet feed is given every day to serve as a high-sugar, high-fat and high-cholesterol feed control, and free food intake and drinking are achieved.

The animals are weighed regularly (respectively at 0, 3, 6, 9 and 12 months), and the serological change is measured by the venous blood sampling of four limbs for monitoring the sugar metabolism and lipid metabolism disorder progress of the body; the magnetic resonance imaging scanning and the liver biopsy pathological detection are carried out regularly, and the magnetic resonance imaging scanning and the liver biopsy pathological detection are used for judging the pathological processes of the liver steatosis and the fibrosis.

Results of the experiment

FIG. 2 is a bar graph of the success rate of the non-human primate model with metabolic fatty liver disease after 12 months of modeling with three high-fat, high-sugar, high-cholesterol feeds in example 1, example 2 and example 3. As can be seen from FIG. 2, different high-fat, high-sugar and high-cholesterol feeding and inducing can obtain a non-human primate model with metabolic-related fatty liver disease, and the modeling rate can reach 72% at least.

FIG. 3 is a histogram of body weight changes in the non-human primate model of example 1 in 0-12 months for the normal diet and three groups of high fat, high sugar and high cholesterol diets in example 1-3 (A1: normal body weight, A2: F1 body weight, A3: body weight, A4: F3 body weight). As can be seen from FIG. 3, the weight of the cynomolgus monkeys fed with the high-fat high-sugar high-cholesterol diet was significantly increased compared to the normal diet, and the increased weight exhibited F1 < F2 < F3, and further, the F3 high-fat high-sugar high-cholesterol diet fed for 3 months caused significant changes in weight due to the increased contents of fat, fructose and cholesterol contained in the diet.

FIG. 4 is a bar graph showing the results of the change of serum glucose in the non-human primate model of metabolic fatty liver disease induced by the normal diet of comparative example 1 and the three groups of high fat, high sugar and high cholesterol diet of examples 1 to 3 within 0-12 months (B1: normal glucose, B2: F1 glucose, B3: F2 glucose, B4: F3 glucose). FIG. 5 is a bar graph showing the results of changes in total serum cholesterol in 0-12 months in the non-human primate model with metabolic fatty liver disease induced by the normal diet of comparative example 1 and the three groups of high fat, high sugar and high cholesterol diets of examples 1-3 (C1: normal total cholesterol, C2: F1 total cholesterol, C3: F2 total cholesterol, C4: F3 total cholesterol). FIG. 6 is a bar graph showing the results of the serum triglyceride changes in the non-human primate model of metabolic fatty liver disease induced by the normal diet of comparative example 1 and the three groups of high fat, high sugar and high cholesterol diets of examples 1 to 3 within 0-12 months (D1: normal triglyceride, D2: F1 triglyceride, D3: F2 triglyceride, D4: F3 triglyceride). As can be seen from fig. 4-6, the total cholesterol level increased at 3 months before molding (0 months per se), and the triglyceride and glucose levels increased significantly at 6-9 months after molding, indicating that the liver in this case had a metabolic disorder of glycolipids.

FIG. 7 is a 12-month liver magnetic resonance imaging scan of a non-human primate model with normal diet of comparative example 1 and three groups of high fat, high sugar, and high cholesterol diet induced metabolic fatty liver disease of examples 1-3 (E: normal liver, G: F1 liver, H: F2 liver, I: F3 liver). The Magnetic Resonance Imaging (MRI) technology is widely applied to liver fat quantification, wherein the Proton Density Fat Fraction (PDFF) technology has high accuracy, good stability and strong repeatability, so the magnetic resonance imaging proton density fat fraction (MRI-PDFF) is used for evaluating liver steatosis. As can be seen from the results in fig. 7, when 12 cynomolgus monkeys were modeled with the high-fat, high-sugar, and high-cholesterol diet, the fat liver image of the model animal showed a larger white area than normal liver, and fat accumulation occurred in the liver of the cynomolgus monkeys (G, H, I in fig. 7).

FIG. 8 is a photograph of HE stained microscopic examination of 12 month liver pathological biopsy of nonhuman primate model (J: normal liver, K: F1 liver, L: F2 liver, M: F3 liver) in the normal diet of comparative example 1 and three groups of high fat, high sugar, and high cholesterol diet-induced metabolic fatty liver disease in examples 1-3.

FIG. 9 is a photograph of Masson's stained microscopic examination of 12-month liver in a non-human primate model (N: normal liver, O: F1 liver, P: F2 liver, QF3 liver) in a normal diet feed in comparative example 1 and three groups of high fat, high sugar, and high cholesterol feeds in examples 1-3. Fig. 8 shows that the modeling of the high-fat high-sugar high-cholesterol diet used can cause liver steatosis (O, P, Q in fig. 8) for 12 months, and fig. 9 shows that the modeling of the high-fat high-sugar high-cholesterol diet used can cause fibrosis pathological changes (K, L, M in fig. 9) for 12 months.

The invention adopts the high-fat high-sugar high-cholesterol feedstuff to construct the metabolic fatty liver disease animal model, which can truly simulate the human physiological and pathological processes of inducing hepatic steatosis and fibrosis lesion caused by abnormal glycolipid metabolism due to unreasonable diet. The model construction method is simple and convenient, has good stability, fills up the blank of the non-human primate model in the field of metabolic fatty liver diseases, and has important significance for developing the research and development of nutrients and medicines in the related fields.

The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.

Claims

1. A method for constructing a non-human primate model with a metabolism-related fatty liver disease is characterized in that a non-human primate is fed with a high-fat high-sugar high-cholesterol feed, so that abnormal glycolipid metabolism of the non-human primate is caused, and then hepatic steatosis and fibrosis are caused, wherein the high-fat high-sugar high-cholesterol feed comprises the following nutritional components in percentage by mass: 17 to 25 weight percent of crude protein, 30 to 45 weight percent of crude fat, 13 to 17 weight percent of crude fiber, 3 to 15 weight percent of fructose, 1 to 3 weight percent of cholesterol, 1 to 4 weight percent of calcium, 0.7 to 1 weight percent of phosphorus, 0.2 to 0.7 weight percent of vitamin and 0.3 to 5 weight percent of mineral.

2. The method of claim 1, wherein the non-human primate is a cynomolgus monkey.

3. The method of claim 1, wherein the non-human primate is aged 5-23 years.

4. The method of claim 1, wherein the non-human primate animal model with metabolic-related fatty liver disease is raised in a single cage.

5. The method for constructing a non-human primate model with metabolic-related fatty liver disease according to claim 1, wherein the high-fat, high-sugar and high-cholesterol diet feeding mode of the cynomolgus monkey is as follows: sufficient high-fat, high-sugar and high-cholesterol feed is supplied, and animals can eat the feed freely for 3-12 months.

6. The method for constructing a non-human primate animal model with metabolic-related fatty liver disease according to claim 1, wherein the nutritional main raw materials of the high-fat, high-sugar and high-cholesterol feed are as follows: the protein is provided by more than one of soybean meal, fish meal and chicken powder, the fat is provided by more than one of corn oil, sunflower seed oil and lard, the carbohydrate is provided by more than one of corn starch, flour and rice flour, and the crude fiber is provided by more than one of bran and rice bran.

7. The method for constructing a non-human primate model with metabolic-related fatty liver disease according to claim 1, wherein the high-fat, high-sugar and high-cholesterol diet comprises the following caloric compositions: 680-1011 Kcal/kg of protein, 2700-4050 Kcal/kg of fat, 960-1160 Kcal/kg of carbohydrate and 4660-5850 Kcal/kg of total calories.

8. The method for constructing a non-human primate animal model with metabolic-related fatty liver disease according to claim 1, wherein the fatty acid composition in the high-fat high-sugar high-cholesterol feed is as follows by mass percent: 30-65 wt% of saturated fatty acid, 10-30 wt% of monounsaturated fatty acid and 15-30 wt% of polyunsaturated fatty acid.

9. The method for constructing a non-human primate animal model with metabolic-related fatty liver disease according to claim 1, wherein the ratio of the fatty acid chain length in the high-fat high-sugar high-cholesterol feed is, in mass percentage: 6.8 to 27.3 weight percent of medium-chain fatty acid and 72.7 to 93.2 weight percent of long-chain fatty acid.

10. The method for constructing a non-human primate animal model with metabolic-related fatty liver disease according to any one of claims 1 to 9, wherein the model is formed after feeding the animal with the high-fat, high-sugar and high-cholesterol feed for 3 to 12 months, the molding rate reaches 72 percent, the weight of the animal model is remarkably increased, and the glucose content, the total cholesterol content and the triglyceride content in blood, which reflect abnormal liver lipid metabolism, are remarkably increased; in the magnetic resonance imaging scanning reflecting liver fat accumulation, the fat accumulation of the model animal is obvious; biopsies reflecting metabolic disease of the liver show severe steatosis with accompanying fibrotic pathological changes.