Application of insulin-like growth factor binding protein-1 in preparation of medicine for treating non-alcoholic fatty liver disease

Abstract

The invention relates to application of insulin-like growth factor binding protein-1 in preparation of drugs for treating non-alcoholic fatty liver diseases, and belongs to the technical field of biological medicines. The invention discloses the new application of the insulin-like growth factor binding protein-1 in preparing the medicine for treating the non-alcoholic fatty liver disease for the first time, effectively proves that the insulin-like growth factor binding protein-1 can effectively reverse liver lipid accumulation caused by Dox, MCDD and HFD, remarkably improves liver injury caused by Dox, MCDD and HFD, and has the advantages that the medicine can be used for treating the non-alcoholic fatty liver disease; the content of triglyceride in the liver and the content of glutamic-pyruvic transaminase and glutamic oxalacetic transaminase in blood are reduced, so that the effect of preventing or treating the non-alcoholic fatty liver disease is achieved. Therefore, the insulin-like growth factor binding protein-1 can be used for preparing the medicine for treating the non-alcoholic fatty liver disease, and has important significance in clinical treatment of the non-alcoholic fatty liver disease in the future.

Description

Technical Field

[0001] The present invention relates to application of insulin-like growth factor binding protein-1 (IGFBP-1) in preparing a drug for treating non-alcoholic fatty liver disease, and belongs to the technical field of biomedicine. Background Art

[0002] Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. In 2024, statistics show that about 38% of adults worldwide are affected by NAFLD. The disease usually manifests as significant liver damage, characterized by lipid deposition and inflammation, and in severe cases may develop into liver fibrosis, cirrhosis and liver cancer. There is increasing evidence that the pathogenesis of NAFLD involves multiple factors, such as insulin resistance, triglyceride (TG) accumulation, changes in intestinal microbiota and interruption of bile acid (BAs) metabolism. Clinically, when patients are diagnosed with NAFLD, they are often treated with oral medications. However, some existing drugs cannot effectively reverse liver lipid accumulation and fibrosis, and the drugs may have some adverse reactions and side effects, such as headache, nausea, insomnia, etc. Therefore, there is an urgent need to find a safe, effective and rapid drug for the treatment of NAFLD in clinical practice.

[0003] Insulin-like growth factor binding proteins (IGFBPs) play a key role in insulin and insulin growth factor signaling and are known to be expressed in a variety of tissues. Studies on the transcriptional regulation of IGFBP genes in various cell types have shown that IGFBPs control both systemic hormones and regulatory factors. Insulin-like growth factor binding protein-1 (IGFBP-1), which is mainly produced in the liver, is one of the six soluble binding proteins that can specifically bind to insulin-like growth factor 1 (IGF-1) and regulate its function and bioavailability. IGFBP-1 is upregulated during fasting, liver regeneration, inflammation, and oxidative stress. Elevated expression of IGFBP-1 inhibits the function of IGF-1 by forming a binary complex with IGF-1, preventing IGF-1 from binding to the IGF-1 receptor or insulin receptor. However, the role of IGFBP-1 in NAFLD is unclear. Whether IGFBP-1 is involved in regulating the occurrence and progression of hepatic lipid accumulation has not been reported. Therefore, it is of great significance to explore the role of IGFBP-1 in the occurrence and development of NAFLD and to clarify that IGFBP-1 becomes a new strategy for the treatment of NAFLD. Summary of the invention

[0004] In view of the deficiencies in the prior art, the purpose of the present invention is to provide the use of insulin-like growth factor binding protein-1 (IGFBP-1) in the preparation of drugs for the treatment of non-alcoholic fatty liver disease. The present invention has found through research that insulin-like growth factor binding protein-1 (IGFBP-1) is involved in regulating the occurrence and progression of liver lipid accumulation in vivo. Specifically, insulin-like growth factor binding protein-1 (IGFBP-1) can significantly reduce liver lipid accumulation and improve liver damage in mice. This shows that IGFBP-1 is expected to become a new treatment for non-alcoholic fatty liver disease.

[0005] The technical solution of the present invention is as follows: Application of insulin-like growth factor binding protein-1 (IGFBP-1) in the preparation of drugs for treating non-alcoholic fatty liver disease.

[0006] Preferably according to the present invention, the non-alcoholic fatty liver disease is non-alcoholic fatty liver disease caused by liver dysfunction and liver lipid accumulation induced by doxorubicin HCl (Dox), or by a methionine and choline deficient diet (Methionineand choline deficient diet, MCDD) or a high-fat diet (High-fat diet, HFD).

[0007] Preferably, according to the present invention, the drug for treating non-alcoholic fatty liver disease alleviates the progression of non-alcoholic fatty liver disease by improving lipid accumulation in the liver.

[0008] Preferably according to the present invention, the drug for treating non-alcoholic fatty liver disease inhibits the progression of non-alcoholic fatty liver disease by reducing triglycerides in the liver and the levels of alanine aminotransferase and aspartate aminotransferase in serum.

[0009] Preferably according to the present invention, in the drug for treating non-alcoholic fatty liver disease, insulin-like growth factor binding protein-1 (IGFBP-1) is the only active ingredient.

[0010] Preferably according to the present invention, the drug for treating non-alcoholic fatty liver disease comprises insulin-like growth factor binding protein-1 (IGFBP-1) and a pharmaceutically acceptable carrier.

[0011] Preferably according to the present invention, the dosage form of the drug for treating non-alcoholic fatty liver disease is granules, tablets, capsules, pills or oral liquid preparations.

[0012] Beneficial effects: The present invention discloses for the first time a new use of insulin-like growth factor binding protein-1 (IGFBP-1) in the preparation of drugs for the treatment of non-alcoholic fatty liver disease. The present invention constructs three non-alcoholic fatty liver disease mouse models (Dox, MCDD and HFD), supplements insulin-like growth factor binding protein-1 (IGFBP-1) by injection, and effectively confirms that insulin-like growth factor binding protein-1 (IGFBP-1) can effectively reverse the liver lipid accumulation caused by Dox, MCDD and HFD, significantly improve the liver damage caused by Dox, MCDD and HFD, reduce the triglyceride content in the liver and the alanine aminotransferase and aspartate aminotransferase content in the blood, thereby achieving the effect of preventing or treating non-alcoholic fatty liver disease. Therefore, insulin-like growth factor binding protein-1 (IGFBP-1) can be used to prepare drugs for the treatment of non-alcoholic fatty liver disease, which is of great significance in the future clinical treatment of non-alcoholic fatty liver disease. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 ELISA was used to detect the IGFBP-1 content in mouse serum after intraperitoneal injection of different doses of IGFBP-1 recombinant protein.

[0014] Figure 2 Diagram showing the construction of three non-alcoholic fatty liver disease mouse models.

[0015] Figure 3 The therapeutic effect of IGFBP-1 in Dox liver injury model mice; In the figure, A is the liver photograph of mice in the Control group, Dox group, IGFBP1 group and IGFBP1+Dox group; B is the detection result of alanine aminotransferase in the serum of mice in the Control group, Dox group, IGFBP1 group and IGFBP1+Dox group; C is the detection result of aspartate aminotransferase in the serum of mice in the Control group, Dox group, IGFBP1 group and IGFBP1+Dox group; D is the results of HE staining and Oil Red O staining of mice in the Control group, Dox group, IGFBP1 group and IGFBP1+Dox group.

[0016] Figure 4 The therapeutic effect of IGFBP-1 in MCDD liver injury model mice; In the figure, A is the liver photograph of mice in the NCD group, NCD+IGFBP1 group, MCDD group and MCDD+IGFBP1 group; B is the detection result of alanine aminotransferase in the serum of mice in the NCD group, NCD+IGFBP1 group, MCDD group and MCDD+IGFBP1 group; C is the detection result of aspartate aminotransferase in the serum of mice in the NCD group, NCD+IGFBP1 group, MCDD group and MCDD+IGFBP1 group; D is the HE staining and Oil Red O staining results of mice in the NCD group, NCD+IGFBP1 group, MCDD group and MCDD+IGFBP1 group.

[0017] Figure 5 The therapeutic effect of IGFBP-1 in HFD liver injury model mice; In the figure, A is the liver photographs, HE staining and Oil Red O staining results of mice in the NCD group, HFD group and HFD+IGFBP1 group; B is the serum alanine aminotransferase detection results of mice in the NCD group, HFD group and HFD+IGFBP1 group; C is the triglyceride detection results in the liver of mice in the NCD group, HFD group and HFD+IGFBP1 group. DETAILED DESCRIPTION

[0018] It should be noted that the following detailed descriptions are illustrative and are intended to provide further explanation of the present application. Unless otherwise specified, all technical and scientific terms used herein have the same meanings as those commonly understood by those skilled in the art to which the present application belongs.

[0019] It should be noted that the terms used herein are only for describing specific embodiments and are not intended to limit the exemplary embodiments according to the present application. As used herein, unless the context clearly indicates otherwise, the singular form is also intended to include the plural form. In addition, it should be understood that when the terms "comprise" and / or "include" are used in this specification, it indicates the presence of features, steps, operations, devices, components and / or combinations thereof.

[0020] The present invention is further described in conjunction with specific examples. The following examples are only for explaining the present invention and are not intended to limit the content thereof. If the specific experimental conditions are not specified in the examples, they are usually carried out according to conventional conditions or the conditions recommended by the reagent company; the reagents and consumables used in the following examples, unless otherwise specified, can all be obtained from commercial sources.

[0021] The present invention is further explained by the following examples, but they are not intended to limit the present invention. It should be understood that these examples are only used to illustrate the present invention and are not intended to limit the scope of the present invention. The experimental methods for the specific conditions in the following examples are usually carried out under normal conditions.

[0022] The technical solution of the present invention is further described below in conjunction with the embodiments, but the protection scope of the present invention is not limited thereto. The reagents and materials involved in the embodiments are all common commercially available products unless otherwise specified.

[0023] Doxorubicin HCl (Dox) used in the examples was purchased from Selleck.

[0024] The insulin-like growth factor binding protein-1 (IGFBP-1) used in the examples was purchased from MCE.

[0025] The alanine aminotransferase (GPT / ALT) activity detection kit and the aspartate aminotransferase (GOT / AST) activity detection kit used in the examples were purchased from Beijing Solebow Technology Co., Ltd.

[0026] The tissue cell triglyceride enzymatic assay kit used in the examples was purchased from Beijing Pulilai Gene Technology Co., Ltd.

[0027] The modified Oil Red O staining kit used in the examples was purchased from Beyotime Biotechnology Research Institute.

[0028] The C57BL6J mice used in the examples were purchased from Beijing Weitonglihua Company.

[0029] The collection and detection of mouse serum and liver tissue specimens used in the examples were approved by the Animal Ethics Committee of Shandong University.

[0030] The experimental data of the present invention were analyzed using GraphPad Prism 6 software, and the differences among different groups were analyzed using t-test. P<0.05 indicated that the difference was statistically significant, and P<0.01 indicated that the difference was statistically significant.

[0031] Example 1: ELISA to evaluate the IGFBP-1 content in mouse serum Twelve 8-week-old C57BL6J mice were randomly divided into four groups. The first group of mice were intraperitoneally injected with PBS buffer, the second group of mice were intraperitoneally injected with 25 μg / kg of IGFBP-1, the third group of mice were intraperitoneally injected with 50 μg / kg of IGFBP-1, and the fourth group of mice were intraperitoneally injected with 100 μg / kg of IGFBP-1. Four hours later, the ELISA kit was used according to the instructions, and the absorbance was detected at 450 nm using an ELISA reader. The standard curve was drawn to calculate the serum IGFBP-1 content. The results are shown in Figure 2. Figure 1 shown.

[0032] Depend on Figure 1It can be seen that intraperitoneal injection of 100 μg / kg IGFBP-1 can significantly increase the IGFBP-1 content in mouse serum.

[0033] Example 2: Construction of a mouse model of non-alcoholic fatty liver disease 1. Animal preparation: 7-week-old C57BL6J mice were placed in the SPF-level animal room of Shandong University and maintained in a normal diet for one week in preparation for subsequent experiments.

[0034] 2. Non-alcoholic fatty liver disease (NAFLD) mouse model: Doxorubicin HCl (Dox), methionine and choline deficient diet (MCDD) or high-fat diet (HFD) are usually used to induce NAFLD in mice.

[0035] 3. Model construction method (1) Dox liver injury model: Dox solution was intraperitoneally injected into mice at a dose of 25 mg / kg, and after three days of culture, Dox liver injury model mice were obtained, which were recorded as the Dox group. The Dox liver injury model mice were caused by Dox inducing liver damage by promoting lipid peroxidation and free radical damage.

[0036] (2) MCDD liver injury model: Mice were fed MCDD feed ad libitum for 4 weeks to obtain MCDD liver injury model mice, which were recorded as the MCDD group. The MCDD model mice were unable to transport triglycerides out of the liver due to lack of methionine (an amino acid necessary for the synthesis of apolipoproteins) and choline, resulting in the accumulation of triglycerides and the formation of fatty liver. At the same time, the lack of choline also caused an increase in reactive oxygen species in the liver mitochondria, leading to liver damage.

[0037] (3) HFD liver injury model: The mice were fed HFD feed ad libitum for 8 weeks to obtain HFD liver injury model mice, which were recorded as the HFD group. The HFD liver injury model mice were due to overnutrition, and the lipids and sugars in the food were completely unable to be absorbed and utilized, and the lipids accumulated in the liver caused fatty liver.

[0038] 4. Insulin-like growth factor binding protein-1 (IGFBP-1) injection (1) IGFBP-1 was intraperitoneally injected into mice at a dose of 100 μg / kg for 3 consecutive days to obtain IGFBP1 group mice; then, the IGFBP1 group mice were used to construct Dox liver injury model mice according to the above method, and IGFBP-1 was injected into Dox liver injury model mice at a dose of 100 μg / kg for 3 consecutive days to obtain IGFBP1+Dox group mice. At the same time, normal mice injected with the same dose of PBS buffer throughout the whole process were used as the blank group, recorded as the Control group.

[0039] (2) The MCDD liver injury model mice were constructed according to the above method, and IGFBP-1 was injected into the MCDD liver injury model mice at a dose of 100 μg / kg for 1 week to obtain the MCDD+IGFBP1 group of mice. At the same time, normal mice injected with the same dose of PBS buffer were used as the blank group, recorded as the NCD group; and NCD group mice injected with the same dose of IGFBP-1 were used as the control group, recorded as the NCD+IGFBP1 group.

[0040] (3) HFD liver injury model mice were constructed according to the above method. IGFBP-1 was injected into the HFD liver injury model mice at a dose of 100 μg / kg for 1 week to obtain HFD+IGFBP1 group mice; normal mice injected with the same dose of PBS buffer were used as the blank group, recorded as the NCD group.

[0041] The construction of the above mouse model and the injection process of insulin-like growth factor binding protein-1 (IGFBP-1) are as follows: Figure 2 shown.

[0042] Example 3. Detection of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and liver tissue staining in mice with Dox liver injury model 1. Blood was collected from the mice in the Control group, Dox group, IGFBP1 group, and IGFBP1+Dox group described in Example 2, item 4 (1) by using the orbital venous blood collection method. The blood samples were allowed to stand for 30 min and then centrifuged at 4000 rpm and 4°C for 10 min to obtain serum.

[0043] The mice in the Control group, Dox group, IGFBP1 group, and IGFBP1+Dox group described in Example 2, point 4 (1) were dissected, and the liver tissues of the mice in each group were collected. Some of the liver tissues were frozen at -80°C, and some of the liver tissues were fixed with 4% paraformaldehyde at room temperature. Frozen sections and paraffin sections were prepared according to existing methods. The livers of the mice in the Control group, Dox group, IGFBP1 group, and IGFBP1+Dox group described in Example 2, point 4 (1) were as follows: Figure 3 As shown in A.

[0044] Depend on Figure 3 As shown in Figure A, Dox can induce severe lipid accumulation in the liver of mice, while IGFBP-1 can reverse this phenomenon.

[0045] 2. Alanine aminotransferase (ALT) test is used to evaluate liver cell damage and liver metabolic function. The specific method is as follows: The mouse sera from the Control group, Dox group, IGFBP1 group, and IGFBP1+Dox group were added to a 96-well plate, and then the sera from each group were tested using a GPT / ALT activity detection kit. The specific detection method was referred to the kit manual. Finally, a standard curve was drawn based on the absorbance detection results at 505 nm to calculate the ALT level in the serum. The results are shown in Figure 3 As shown in B.

[0046] 3. Aspartate aminotransferase (AST) test is used to evaluate liver cell damage and liver metabolic function. The specific method is as follows: The mouse sera from the Control group, Dox group, IGFBP1 group, and IGFBP1+Dox group were added to a 96-well plate, and then the sera from each group were tested using a GOT / AST activity detection kit. The specific detection method was referred to the kit manual. Finally, a standard curve was drawn based on the absorbance detection results at 505 nm to calculate the level of AST in the serum. The results are shown in the figure. Figure 3 As shown in C.

[0047] Depend on Figure 3 Medium B and Figure 3 As shown in Figure C, IGFBP-1 significantly improved Dox-induced liver injury.

[0048] 4. Oil Red O staining of liver: The frozen sections of liver tissues of the Control group, Dox group, IGFBP1 group and IGFBP1+Dox group were rewarmed at room temperature for 20 minutes, and the staining washing solution was added for 20 seconds, and then the washing solution was removed. Then, the Oil Red O staining solution was added dropwise, and the sections were stained for 25 minutes, washed for 30 seconds, stained with hematoxylin for 3 minutes, differentiated with 1% hydrochloric acid alcohol for 1 second, washed with water, and immersed in tap water for 3 minutes to turn blue. After sealing, the sections were observed under a microscope and photographed; Liver HE staining: The paraffin sections of liver tissues of the Control group, Dox group, IGFBP1 group and IGFBP1+Dox group were routinely dewaxed to water, stained with hematoxylin staining solution for 3 min, rinsed with running water, and the staining degree was observed under a microscope; differentiated with 1% hydrochloric acid alcohol for 1 s, washed with water, immersed in tap water for 3 min to turn blue, and the color was observed under a microscope; eosin staining solution was added, stained for 3 min, washed with distilled water and observed under a microscope, and rapidly dehydrated with a series of ethanol starting from 75%, made transparent with xylene, and sealed with neutral gum before observation and photography under a microscope.

[0049] The results of Oil Red O staining and HE staining are as follows Figure 3 As shown in D.

[0050] Depend on Figure 3 As shown in Figure 5D, IGFBP-1 significantly improved liver damage and liver lipid accumulation.

[0051] Example 4. Detection of ALT and AST in serum and liver tissue staining of MCDD liver injury model mice 1. Blood was collected from the NCD group, NCD+IGFBP1 group, MCDD group, and MCDD+IGFBP1 group of mice described in Example 2, point 4 (2) by using the orbital venous blood sampling method. The blood samples were allowed to stand for 30 min and then centrifuged at 4000 rpm and 4°C for 10 min to obtain serum.

[0052] The mice in the NCD group, NCD+IGFBP1 group, MCDD group, and MCDD+IGFBP1 group described in Example 2, Section 4 (2) were dissected, and the liver tissues of the mice in each group were collected. Some of the liver tissues were frozen at -80°C, and some of the liver tissues were fixed with 4% paraformaldehyde at room temperature. Frozen sections and paraffin sections were prepared according to existing methods. The livers of the mice in the NCD group, NCD+IGFBP1 group, MCDD group, and MCDD+IGFBP1 group described in Example 2, Section 4 (2) were as follows: Figure 4 As shown in A.

[0053] Depend on Figure 4 As shown in Figure A, MCDD can induce severe lipid accumulation in the liver of mice, while IGFBP-1 can reverse this phenomenon.

[0054] 2. Alanine aminotransferase (ALT) was tested to evaluate liver cell damage and liver metabolic function. The specific method was the same as in Example 3. The results were as follows: Figure 4 As shown in B.

[0055] 3. Aspartate aminotransferase (AST) was tested to evaluate liver cell damage and liver metabolic function. The specific method was the same as in Example 3. The results were as follows: Figure 4 As shown in C.

[0056] Depend on Figure 4 Medium B and Figure 4 As shown in Figure C, IGFBP-1 significantly improved MCDD-induced liver injury.

[0057] 4. Oil Red O staining of liver: The frozen sections of liver tissues of the NCD group, NCD+IGFBP1 group, MCDD group, and MCDD+IGFBP1 group were stained with Oil Red O according to the method described in Example 3 and then observed and photographed under a microscope; Liver HE staining: According to the method described in Example 3, the liver tissue paraffin sections of the NCD group, NCD+IGFBP1 group, MCDD group and MCDD+IGFBP1 group were HE stained and observed under a microscope and photographed.

[0058] The results of Oil Red O staining and HE staining are as follows Figure 4 As shown in D.

[0059] Depend on Figure 4 As shown in Figure 5D, IGFBP-1 significantly improved liver damage and liver lipid accumulation.

[0060] Example 5. Detection of ALT in Serum, Liver Tissue Staining and Determination of Triglyceride (TG) Content in Liver Tissue of HFD Liver Injury Model Mice 1. Blood was collected from the mice in the NCD group, HFD group, and HFD+IGFBP1 group described in Example 2, point 4 (3) by using the orbital venous blood collection method. The blood samples were allowed to stand for 30 min and then centrifuged at 4000 rpm and 4°C for 10 min to obtain serum.

[0061] The mice in the NCD group, HFD group, and HFD+IGFBP1 group described in Item 4 (3) of Example 2 were dissected, and liver tissues of the mice in each group were collected. Some of the liver tissues were frozen at -80°C, and some of the liver tissues were fixed with 4% paraformaldehyde at room temperature. Frozen sections and paraffin sections were prepared according to existing methods.

[0062] Liver Oil Red O staining: The frozen sections of liver tissues of the NCD group, HFD group, and HFD+IGFBP1 group were stained with Oil Red O according to the method described in Example 3 and then observed and photographed under a microscope; Liver HE staining: According to the method described in Example 3, the liver tissue paraffin sections of the NCD group, HFD group and HFD+IGFBP1 group were HE stained and observed under a microscope and photographed.

[0063] The liver photos, HE staining and Oil Red O staining of the mice in the NCD group, HFD group and HFD+IGFBP1 group described in Example 2, point 4 (3) are as follows: Figure 5 As shown in A.

[0064] Depend on Figure 5 As shown in Figure A, HFD can induce severe lipid accumulation in the liver of mice, while IGFBP-1 can reverse this phenomenon, and IGFBP-1 significantly improves liver damage and liver lipid accumulation.

[0065] 2. Alanine aminotransferase (ALT) was tested to evaluate liver cell damage and liver metabolic function. The specific method was the same as in Example 3. The results were as follows: Figure 5 As shown in B.

[0066] Depend on Figure 5 As shown in Figure 3, ALT in the liver of mice in the HFD+IGFBP1 group was significantly downregulated compared with that in the HFD group, indicating that IGFBP-1 improved HFD-induced liver damage.

[0067] 3. Determination of triglyceride (TG) content in liver tissue The liver tissues of mice in the NCD group, HFD group, and HFD+IGFBP1 group were accurately weighed, and lysed and homogenized according to the ratio of 1 mg tissue to 20 μl lysis buffer. The supernatant was collected after standing and tested using a tissue cell triglyceride enzymatic assay kit. The specific detection method was referred to the kit manual. Finally, a standard curve was drawn based on the absorbance detection results at 550 nm to calculate the TG content in the liver tissue. The results are shown in Figure 5 As shown in C.

[0068] Depend on Figure 5 As shown in Figure C, IGFBP-1 significantly reduced the triglyceride content in the liver.

[0069] In summary, insulin-like growth factor binding protein-1 (IGFBP-1) can improve liver damage caused by methods such as doxorubicin hydrochloride, methionine and choline deficient diet and high-fat diet, and inhibit liver lipid accumulation. This shows that IGFBP-1 is expected to become a safe, effective and rapid drug for the treatment of NAFLD in clinical practice, breaking the defects of current traditional treatment methods, and has important significance in the clinical treatment of non-alcoholic fatty liver disease in the future.

[0070] The above-described embodiments are only preferred specific implementation schemes of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. Application of insulin-like growth factor binding protein-1 in the preparation of drugs for the treatment of non-alcoholic fatty liver disease.

2. The use according to claim 1, characterized in that The non-alcoholic fatty liver disease is non-alcoholic fatty liver disease caused by a methionine and choline deficient diet or a high-fat diet.

3. The use according to claim 1, characterized in that The drug for treating non-alcoholic fatty liver disease alleviates the progression of non-alcoholic fatty liver disease by improving lipid accumulation in the liver.

4. The use according to claim 1, characterized in that The drug for treating non-alcoholic fatty liver disease inhibits the progression of non-alcoholic fatty liver disease by reducing triglycerides in the liver and the contents of alanine aminotransferase and aspartate aminotransferase in serum.

5. The use according to claim 1, characterized in that In the drug for treating non-alcoholic fatty liver disease, insulin-like growth factor binding protein-1 is the only active ingredient.

6. The use according to claim 1, characterized in that The drug for treating non-alcoholic fatty liver disease comprises insulin-like growth factor binding protein-1 and a pharmaceutically acceptable carrier.

7. The use according to claim 1, characterized in that The dosage form of the drug for treating non-alcoholic fatty liver disease is granules, tablets, capsules, pills or oral liquid preparations.

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