Application of Sdccag3 gene in preparation of weight-reducing medicine for regulating obesity phenotype and glycolipid metabolism
By overexpressing the Sdccag3 gene in mice, regulating the obesity phenotype and glycolipid metabolism, the problem of difficulty in effectively treating obesity and its metabolic disorders in the prior art was solved, and significant weight loss and metabolic improvement effects were achieved.
Patent Information
- Application Number
- CN202411410532.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-10-10
- Publication Date
- 2025-02-18
- Estimated Expiration
- Not applicable · inactive patent
AI Technical Summary
The prior art is difficult to effectively treat or alleviate obesity and its metabolic disorders caused, especially problems such as dyslipidemia and insulin resistance.
By establishing a Sdccag3 adipose tissue-specific overexpression vector, verifying that its overexpression in mice can regulate obesity phenotype and glycolipid metabolism, and preparing or screening drugs or preparations that regulate Sdccag3 gene expression are used to prepare lipid-lowering and weight-loss drugs. .
Significantly improve the weight and fat size and distribution of obese mice, inhibit the increase in blood lipid levels, improve glucose tolerance and insulin sensitivity, and effectively regulate the obesity phenotype and glycolipid metabolism, and achieve weight loss effect.
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Figure CN119454960A_ABST
Abstract
Description
Technical Field
[0001] The invention relates to application of Sdccag3 gene in preparing weight-loss medicine for regulating obesity phenotype and glucose and lipid metabolism, and belongs to the field of molecular biology and biotechnology. Background Art
[0002] With the development of social economy and the change of people's lifestyle, the global obesity rate has been on a continuous upward trend. In the past 40 years, the number of obese people in the world has increased alarmingly, and now the number of obese adults in the world exceeds that of underweight people. Obesity is a chronic metabolic disease, which is mainly characterized by excessive accumulation of body fat and overweight. Severe obesity often occurs simultaneously with diseases such as dyslipidemia, non-alcoholic fatty liver, hypertension, coronary heart disease, impaired glucose tolerance or diabetes. In addition, obesity can cause the occurrence and development of oral periodontitis by affecting the level of inflammatory factors and inducing oxidative stress. It can also directly attack the alveolar bone, promote the formation of osteoclasts in bone tissue, lead to bone loss, and endanger oral health. Chronic metabolic diseases caused by obesity have caused increasingly huge social medical expenditures and become a major burden on public health. However, the treatment methods and means for treating or alleviating obesity and the metabolic disorders it causes are still very limited.
[0003] Obesity is the result of an imbalance between the body's energy intake and consumption. Excess energy is stored as fat in the body's adipose tissue. When the storage capacity of the tissue is overwhelmed, the endocrine dysfunction of the adipose tissue leads to metabolic disorders, and the function of the adipose tissue declines, leading to ectopic fat accumulation and lipotoxic metabolic stress in other metabolically sensitive organs such as muscle, liver, and heart, thereby promoting inflammation and metabolic dysfunction in the liver, skeletal muscle, and heart, and continuously increasing blood glucose and lipid levels, and promoting insulin resistance. Severe obesity often occurs simultaneously with diseases such as dyslipidemia, type 2 diabetes, and non-alcoholic fat, and increases the risk of cardiovascular disease. Due to complex metabolic changes in multiple tissues, pharmacological treatment of obesity and related metabolic disorders will be more challenging.
[0004] Obesity is closely related to lipid metabolism disorders, which directly or indirectly lead to adverse metabolic outcomes. Elevated total cholesterol (CHO), triglycerides (TG) and low-density lipoprotein cholesterol (LDLC) are used to measure metabolic health status and disease risk. Many studies have shown that the levels of blood cholesterol and triglycerides in obese patients are higher than those in normal weight, and the body mass index (BMI) is positively correlated with total cholesterol, triglycerides and low-density lipoprotein cholesterol. At the same time, among the metabolic disorders related to obesity, insulin resistance and glucose tolerance are clinically important because they are closely related to a variety of diseases such as type 2 diabetes, hypertension, dyslipidemia, coagulation and fibrinolysis disorders, all of which are independent risk factors for cardiovascular diseases (heart attack, stroke and peripheral arterial disease). At the same time, increased serum free fatty acid levels are an important cause of obesity-related insulin resistance. Therefore, finding factors that can stabilize lipid metabolism homeostasis is of great significance for the control and treatment of obesity.
[0005] Serologically defined colon cancer antigen 3 (Sdccag3) is a 45kd protein with a coiled-coil domain. Studies have shown that it has biological functions such as protein transport, mitosis, ciliogenesis, and osteogenesis. Currently, there are no reports on the function of Sdccag3 in fat metabolism-related diseases, especially the function of Sdccag3 in regulating obesity phenotype and glucose and lipid metabolism. Summary of the invention
[0006] In view of the deficiencies of the prior art, the present invention provides the use of the Sdccag3 gene in the preparation of a weight-loss drug for regulating obesity phenotype and glucose and lipid metabolism. The present invention establishes a Sdccag3 adipose tissue-specific overexpression vector, verifies that it can regulate the obesity phenotype and related serum biochemical indicators of mice, and can use the gene as a drug target for regulating obesity phenotype and glucose and lipid metabolism, and for the preparation of lipid-lowering and weight-loss drugs.
[0007] The technical solution of the present invention is as follows:
[0008] The use of the Sdccag3 gene in the preparation of a weight-loss drug for regulating obesity phenotype and glucose and lipid metabolism, wherein the nucleotide sequence of the Sdccag3 gene is shown in SEQ ID No. 1.
[0009] Preferably, according to the present invention, the use of the Sdccag3 gene in the preparation of a weight loss drug for regulating obesity phenotype and glucose and lipid metabolism includes the following two aspects:
[0010] (1) Using the Sdccag3 gene as a target for the preparation of weight loss drugs that regulate obesity phenotype and glucose and lipid metabolism;
[0011] (2) The Sdccag3 gene is used as a target for the screening of weight loss drugs that regulate obesity phenotype and lipid metabolism.
[0012] Preferably according to the present invention, the Sdccag3 gene is used as a target for the preparation of weight loss drugs for regulating obesity phenotype and glucose and lipid metabolism, which means: using the Sdccag3 gene as a target of the drug or preparation, increasing the expression level of the Sdccag3 gene in adipose tissue, to develop weight loss drugs or preparations for regulating obesity phenotype and glucose and lipid metabolism.
[0013] Preferably according to the present invention, the use of the Sdccag3 gene as a target for screening weight loss drugs that regulate obesity phenotype and glucose and lipid metabolism refers to: using the Sdccag3 gene as a target for drugs or preparations, screening the drugs or preparations to find drugs or preparations that can promote the expression of the Sdccag3 gene in adipose tissue as alternative weight loss drugs or preparations for regulating obesity phenotype and glucose and lipid metabolism.
[0014] Preferably according to the present invention, the drug for regulating obesity phenotype includes but is not limited to: nucleic acid molecules, carbohydrates, lipids, small molecule chemical drugs, antibody drugs, polypeptides, proteins or viruses.
[0015] Further preferably, the weight loss drug for regulating obesity phenotype and glucose and lipid metabolism is a Sdccag3 adipose tissue-specific overexpression adeno-associated virus vector, whose effective ingredient contains the nucleotide sequence shown in SEQ ID No.1, and is specifically prepared by co-transfecting host cells with a recombinant expression plasmid and a packaging system. Overexpression of the Sdccag3 gene inhibits the increase in blood lipid levels, reduces the size of the fat volume of obese mice, and reduces the levels of serum triglycerides, cholesterol and low-density lipoprotein cholesterol in obese mice, thereby reducing blood sugar, serum free fatty acids and serum insulin levels, and promoting glucose tolerance and insulin sensitivity.
[0016] Preferably according to the present invention, the weight loss drug for regulating obesity phenotype and glucose and lipid metabolism further contains a pharmaceutically acceptable excipient.
[0017] More preferably, the excipient is one or more of glucose, sucrose, sorbitol, mannose, starch, microcrystalline cellulose, polyvinyl pyrrolidone, cellulose and water.
[0018] Preferably according to the present invention, the weight loss drug for regulating obesity phenotype and glucose and lipid metabolism is in the form of tablets, pills, powder or injection.
[0019] Technical features and beneficial effects of the present invention:
[0020] 1. The present invention first verifies the effect of Sdccag3 overexpression on the weight, fat size and distribution of mice with obesity, and finds that overexpression of Sdccag3 can significantly improve the weight, fat size and distribution of obese mice. Then, the effect of adeno-associated virus vectors with Sdccag3 adipose tissue-specific overexpression on blood lipid metabolism levels, glucose tolerance and insulin sensitivity in mice is verified, and it is found that overexpression of Sdccag3 can significantly inhibit the increase in blood lipid levels induced by obesity in mice, and overexpression of Sdccag3 can also significantly improve glucose intolerance and increase insulin sensitivity, thereby providing a theoretical basis for the preparation or screening of drugs or preparations that promote Sdccag3 gene expression as alternative weight-loss drugs or preparations for regulating obesity phenotypes and glucose and lipid metabolism.
[0021] 2. The present invention injects Sdccag3 adipose tissue-specific overexpression adeno-associated virus vector and control adeno-associated virus vector, and finds that specific overexpression of Sdccag3 in adipose tissue of mice can significantly inhibit the increase of blood lipid levels, reduce the size of fat volume of obese mice, reduce the levels of serum triglycerides, cholesterol and low-density lipoprotein cholesterol in obese mice, improve glucose intolerance, increase insulin sensitivity, effectively regulate obesity phenotype and glucose and lipid metabolism, achieve weight loss effect, and can be used to prepare lipid-lowering and weight loss drugs.
[0022] 3. The present invention uses the Sdccag3 gene as a target to prepare or screen weight loss drugs that regulate obesity phenotype and glucose and lipid metabolism. Drug screening is mainly for unknown drugs, and the drugs act on the target gene. According to whether the drug can promote the expression of the target gene, weight loss drugs that regulate obesity phenotype and glucose and lipid metabolism are screened; drug preparation is mainly based on the target gene, and targeted weight loss drugs that regulate obesity phenotype and glucose and lipid metabolism are prepared or constructed to promote the expression of the target gene; the screened or prepared drugs are of great significance in regulating obesity phenotype, glucose and lipid metabolism and weight loss. BRIEF DESCRIPTION OF THE DRAWINGS
[0023] Figure 1 This is a schematic diagram of the comparison results of mouse body shapes after Sdccag3 overexpression was specifically overexpressed in mouse adipose tissue using a Sdccag3 overexpression adeno-associated virus vector.
[0024] Figure 2 This is a schematic diagram of the changes in mouse weight gain after Sdccag3 overexpression was achieved specifically in mouse adipose tissue using a Sdccag3 overexpression adeno-associated virus vector.
[0025] Figure 3 This is a schematic diagram of the Micro-CT scan reconstruction results of mouse abdominal fat after using Sdccag3 overexpression adenovirus vector to overexpress Sdccag3 specifically in mouse adipose tissue.
[0026] Figure 4 This is a schematic diagram of the comparison results of mouse epididymal adipose tissue after Sdccag3 overexpression was achieved specifically in mouse adipose tissue using Sdccag3 overexpression adenovirus vector.
[0027] Figure 5 This is a schematic diagram of the results of epididymal adipose tissue weight in mice after Sdccag3 overexpression was specifically overexpressed in mouse adipose tissue using Sdccag3 overexpression adenovirus vector.
[0028] Figure 6 This is a schematic diagram of the ratio of epididymal adipose tissue to body weight in mice after Sdccag3 overexpression was achieved in adipose tissue of mice using a Sdccag3 overexpression adenovirus vector.
[0029] Figure 7 This is a schematic diagram of the results of serum triglyceride (TG) content in mice after Sdccag3 was overexpressed specifically in mouse adipose tissue using a Sdccag3 overexpression adenovirus vector.
[0030] Figure 8 This is a schematic diagram of the results of total cholesterol (CHO) content in mouse serum after Sdccag3 was overexpressed specifically in mouse adipose tissue using a Sdccag3 overexpression adenovirus vector.
[0031] Fig. 9 This is a schematic diagram of the results of low-density lipoprotein cholesterol (LDLC) content in mouse serum after Sdccag3 was overexpressed specifically in mouse adipose tissue using Sdccag3 overexpression adenovirus vector.
[0032] Fig.10 This is a schematic diagram of the results of free fatty acids (FFA) in mouse serum after Sdccag3 was overexpressed specifically in mouse adipose tissue using a Sdccag3 overexpression adenovirus vector.
[0033] Fig.11 This is a schematic diagram of the fasting serum insulin results of mice after Sdccag3 was overexpressed specifically in mouse adipose tissue using a Sdccag3 overexpression adenovirus vector.
[0034] Fig.12 This is a schematic diagram of the fasting blood glucose results of mice after Sdccag3 was overexpressed specifically in mouse adipose tissue using a Sdccag3 overexpression adenovirus vector.
[0035] Fig.13 This is a schematic diagram of the results of the glucose tolerance test in mice after Sdccag3 was overexpressed specifically in mouse adipose tissue using a Sdccag3 overexpression adenovirus vector.
[0036] Fig.14This is a schematic diagram of the results of the insulin tolerance test in mice after Sdccag3 overexpression was achieved specifically in mouse adipose tissue using a Sdccag3 overexpression adenovirus vector. DETAILED DESCRIPTION
[0037] The present invention is further described below in conjunction with examples, which are only used to illustrate the present invention but not to limit the scope of protection of the present invention.
[0038] Unless otherwise specified, the drugs and reagents involved in the examples are all common commercially available products; the experimental operations involved in the examples are all carried out according to routine operations in the art unless otherwise specified.
[0039] The Sdccag3 adipose tissue-specific overexpression adeno-associated virus vector used in the present invention is rAAV9-FABP4p-MCS-SDCCAG3-SV40, whose active ingredient contains the nucleotide sequence shown in SEQ ID No. 1, and is available from Shanghai Genetech Co., Ltd. The adeno-associated virus empty vector used as a control is also available from Shanghai Genetech Co., Ltd.
[0040] Example 1. Establishment of animal model
[0041] Thirty-two 4-week-old male C57BL / 6J mice were randomly divided into 4 groups. The adeno-associated virus vector (rAAV9-FABP4p-MCS-SDCCAG3-SV40) specifically overexpressing Sdccag3 adipose tissue was dissolved on ice and diluted with sterile saline. The injection site in the abdomen of the mice was disinfected with iodine. The adipose tissue of the mice in groups 1 and 2 was infected by intraperitoneal injection. At the same time, the mice in groups 3 and 4 were injected with empty adeno-associated virus vectors as the control group. After 2 weeks of feeding observation, the mice in groups 1 and 3 were fed with ordinary feed, recorded as NCD-AAV-SDCCAG3 and NCD-AAV-NC mice, and the mice in groups 2 and 4 were fed with high-fat feed, recorded as HFD-AAV-SDCCAG3 and HFD-AAV-NC mice. All mice in the experiment were housed in sterilized standard cages with a 12-h light-dark cycle and provided with free access to drinking water and corresponding standard diets. After 16 weeks of feeding, normal mouse models (NCD-AAV-SDCCAG3 and NCD-AAV-NC) and high-fat mouse models (HFD-AAV-SDCCAG3 and HFD-AAV-NC) were obtained.
[0042] The NCD-AAV-NC, NCD-AAV-SDCCAG3, HFD-AAV-NC, and HFD-AAV-SDCCAG3 mice fed with the above-mentioned diet for 16 weeks were taken, photographed, and weighed after anesthesia. Figures 1-2 shown.
[0043] Depend on Figures 1-2 It can be seen that there is no significant difference in body size and weight between the NCD-AAV-NC and NCD-AAV-SDCCAG3 groups of mice, and the HFD-AAV-SDCCAG3 mice are significantly smaller in body size and lighter in weight than the HFD-AAV-NC mice. This indicates that overexpression of Sdccag3 did not change the weight development of mice under a normal diet, but inhibited the weight gain of mice caused by obesity due to high-fat diet feeding. That is, overexpression of Sdccag3 can effectively attenuate the development of obesity induced by a high-fat diet in mice.
[0044] Example 2: Micro-CT scanning and reconstruction of mice
[0045] Micro-CT scan reconstruction of abdominal fat was performed on the NCD-AAV-SDCCAG3, NCD-AAV-NC mice and HFD-AAV-SDCCAG3, HFD-AAV-NC mice constructed in Example 1, and the analysis results were as follows: Figure 3 shown.
[0046] The specific process is as follows: Micro-computed tomography (micro CT) was performed using the Quantum GX2 Liveanimal Imaging System (PerkinElmer, Japan), and the abdomen and lower limbs of c57 were scanned at a resolution of 72 microns to obtain DICOM files. The obtained DICOM files were analyzed using Mimics Research 21.0. The abdomen and lower limbs of c57 were selected to analyze the distribution of visceral fat and subcutaneous fat, and the CT value of adipose tissue was -187 to -22HU. With the edge of the abdominal cavity as the boundary, the adipose tissue in the abdominal cavity is visceral fat, represented by orange, and the adipose tissue outside the abdominal cavity is subcutaneous fat, represented by green. They were separated by Split Mask to obtain the distribution of visceral fat and subcutaneous fat in the sagittal plane (anatomical landmark reference: penis bone), coronal plane (anatomical landmark reference: bladder and testicles) and horizontal plane (anatomical landmark reference: external oblique muscle).
[0047] Depend on Figure 3 It can be seen that there is no significant difference in abdominal fat distribution between the NCD-AAV-NC and NCD-AAV-SDCCAG3 groups of mice, while the HFD-AAV-SDCCAG3 mice have significantly less abdominal fat distribution and smaller volume than the HFD-AAV-NC group of mice. This indicates that overexpression of Sdccag3 did not change the abdominal fat distribution of mice under a normal diet, while high-fat diet feeding led to an inhibitory effect on the distribution and volume of abdominal fat. In other words, overexpression of Sdccag3 can effectively inhibit the distribution of abdominal fat in mice induced by a high-fat diet and reduce the volume of abdominal fat in mice induced by a high-fat diet.
[0048] Example 3: Collection of epididymal adipose tissue
[0049] The NCD-AAV-SDCCAG3, NCD-AAV-NC mice and HFD-AAV-SDCCAG3, HFD-AAV-NC mice constructed in Example 1 were killed by cervical dislocation. The mouse testicles were found in the lower abdomen and lifted up with tweezers. The white fat attached to them was epididymal fat, which was peeled off along the vas deferens to the end of the testicle and then cut off. After each sample was taken out, it was rinsed with sterile PBS solution, and the water was absorbed with absorbent paper.
[0050] The epididymal adipose tissue was weighed and photographed. Figures 4 to 6 shown.
[0051] Depend on Figures 4 to 6 It can be seen that there was no significant difference in the size, weight and epididymal fat tissue / body weight ratio between the NCD-AAV-NC and NCD-AAV-SDCCAG3 groups of mice, while the epididymal fat tissue size and weight of HFD-AAV-SDCCAG3 mice were significantly smaller than those of the HFD-AAV-NC group, and the epididymal fat tissue / body weight ratio was significantly reduced. This indicates that overexpression of Sdccag3 did not change the size, weight and epididymal fat tissue / body weight ratio of mice under normal diet, but reduced the size, weight and epididymal fat tissue / body weight ratio of mice fed with a high-fat diet. That is, overexpression of Sdccag3 can effectively inhibit the growth of fat tissue induced by a high-fat diet in mice.
[0052] Example 4. Mouse serum collection and biochemical analysis
[0053] The NCD-AAV-SDCCAG3, NCD-AAV-NC mice and HFD-AAV-SDCCAG3, HFD-AAV-NC mice constructed in Example 1 were killed by cervical dislocation. Before the blood coagulated, blood was collected from the angular venous plexus using a capillary glass tube with an inner diameter of 0.3 mm. The blood samples were allowed to stand overnight at 4 degrees Celsius and then centrifuged at 4000 r / min for 15 minutes to separate the upper serum into new collection tubes, which were then packaged and stored at -80 degrees Celsius.
[0054] The above serum samples were taken for biochemical analysis. Serum triglyceride, cholesterol, low-density lipoprotein cholesterol were measured using commercial kits (S03030; S03040; S03027; S03042; S03025; S03029, Raydu, China) and automatic biochemical analyzer (Chemray 800, Raydu, China). Serum free fatty acids were measured using a free fatty acid content detection kit (BC0590, Solebao, China). Serum insulin was measured using a mouse insulin ELISA kit (SEKM-0141, Solebao, China) according to the commercial instructions. The results are shown in the figure. Figures 7 to 11 shown.
[0055] Depend on Figures 7 to 11 It can be seen that there were no significant differences in serum triglycerides, cholesterol, low-density fat white cholesterol, free fatty acids and insulin between the NCD-AAV-NC and NCD-AAV-SDCCAG3 groups of mice, while the serum triglycerides, cholesterol, low-density fat white cholesterol levels, free fatty acids and insulin levels of HFD-AAV-SDCCAG3 mice were lower than those of the HFD-AAV-NC group. This indicates that overexpression of Sdccag3 failed to affect the serum triglycerides, cholesterol, low-density fat white cholesterol, free fatty acids and insulin levels of mice on a normal diet, but inhibited the increase in serum triglycerides, cholesterol, low-density fat white cholesterol levels induced by a high-fat diet, reduced free fatty acids and reduced insulin levels. That is, overexpression of Sdccag3 can effectively inhibit the increase in serum biochemical indicators related to obesity.
[0056] Example 5: Blood glucose detection in mice
[0057] The NCD-AAV-SDCCAG3, NCD-AAV-NC mice and HFD-AAV-SDCCAG3, HFD-AAV-NC mice constructed in Example 1 were fasted for 12 hours before the experiment, and were kept drinking water normally. The tail vein blood test method was used. At the beginning of the experiment, the mice were placed in a fixture, the tails were fully exposed, the tip of the tail was wiped and disinfected with an alcohol cotton ball, the tip of the tail vein was punctured with a disposable peripheral blood collector, a drop of blood was wiped off, and the second drop of blood was collected with a blood glucose test strip, and then placed in a blood glucose meter for measurement. Read and record the results. Fig.12 shown.
[0058] Depend on Fig.12It can be seen that there is no significant difference in blood glucose levels between the NCD-AAV-NC and NCD-AAV-SDCCAG3 groups of mice, while the blood glucose levels of HFD-AAV-SDCCAG3 mice are significantly lower than those of HFD-AAV-NC mice. This indicates that overexpression of Sdccag3 failed to affect the blood glucose levels of mice under a normal diet, while the blood glucose levels induced by a high-fat diet were significantly reduced. In other words, overexpression of Sdccag3 can effectively inhibit the increase in blood glucose levels induced by a high-fat diet.
[0059] Example 6. Glucose tolerance test in mice
[0060] The NCD-AAV-SDCCAG3, NCD-AAV-NC mice and HFD-AAV-SDCCAG3, HFD-AAV-NC mice constructed in Example 1 were fasted for 16 hours before the experiment and maintained normal drinking water. At the beginning of the experiment, each mouse was weighed first, and blood glucose test strips were used to collect blood from the tip of the mouse's tail vein. The blood glucose value was measured with a blood glucose meter and recorded as the blood glucose value at 0 min. After the mice adapted for 30 min, 20% glucose solution was prepared with normal saline at a dosage of 2 g / kg. The injection volume was 0.1 ml / g, and the glucose solution was injected intraperitoneally. The blood glucose level was measured and recorded at 15 min, 30 min, 60 min, and 120 min after the injection. The results are shown as follows Fig.13 shown.
[0061] Depend on Fig.13 It can be seen that there is no significant difference in glucose tolerance between the NCD-AAV-NC and NCD-AAV-SDCCAG3 groups of mice, while the blood glucose of HFD-AAV-SDCCAG3 mice did not rise significantly after intraperitoneal injection of glucose, and recovered to the basal level faster than that of HFD-AAV-NC group mice. This indicates that overexpression of Sdccag3 did not affect the glucose tolerance of mice on a normal diet, but made the glucose tolerance of mice fed a high-fat diet tend to normal. That is, overexpression of Sdccag3 can effectively improve glucose intolerance induced by a high-fat diet.
[0062] Example 7, Insulin tolerance test in mice
[0063] The NCD-AAV-SDCCAG3, NCD-AAV-NC mice and HFD-AAV-SDCCAG3, HFD-AAV-NC mice constructed in Example 1 were fasted for 4 hours before the experiment and maintained normal drinking water. At the beginning of the experiment, each mouse was weighed first, and blood glucose test strips were used to collect blood from the tip of the mouse tail vein. The blood glucose value was measured with a blood glucose meter and recorded as the blood glucose value at 0 min. After the mice adapted for 30 min, they were intraperitoneally injected with insulin at a dosage of 0.5 U / kg. The blood glucose levels were measured and recorded at 15 min, 30 min, 60 min, and 120 min after the injection. The results are shown as follows Fig.14 shown.
[0064] Depend on Fig.14 It can be seen that there is no significant difference in insulin sensitivity between the NCD-AAV-NC and NCD-AAV-SDCCAG3 groups of mice, while the blood sugar of HFD-AAV-SDCCAG3 mice decreased significantly after intraperitoneal injection of insulin compared with the HFD-AAV-NC group of mice, and recovered to the basal level more slowly, which can be significantly controlled by insulin. This shows that overexpression of Sdccag3 failed to affect the insulin sensitivity of mice under normal diet, but weakened the insulin resistance of mice fed with high-fat diet. That is, overexpression of Sdccag3 can effectively improve the insulin sensitivity induced by high-fat diet.
[0065] The preferred embodiments of the present invention are described in detail above, but the present invention is not limited thereto. Within the technical concept of the present invention, the technical solution of the present invention can be subjected to a variety of simple modifications, including the combination of various technical features in any other suitable manner, and these simple modifications and combinations should also be regarded as the contents disclosed by the present invention and belong to the protection scope of the present invention.
Claims
1. Application of the Sdccag3 gene in the preparation of a weight loss drug for regulating obesity phenotype and glucose and lipid metabolism, characterized in that: The nucleotide sequence of the Sdccag3 gene is shown in SEQ ID No.
1.
2. The use according to claim 1, characterized in that The application of the Sdccag3 gene in the preparation of a weight loss drug for regulating obesity phenotype and glucose and lipid metabolism includes the following two aspects: (1) Using the Sdccag3 gene as a target for the preparation of weight loss drugs that regulate obesity phenotype and glucose and lipid metabolism; (2) The Sdccag3 gene is used as a target for the screening of weight loss drugs that regulate obesity phenotype and lipid metabolism.
3. The use according to claim 2, characterized in that The Sdccag3 gene is used as a target for the preparation of a weight loss drug for regulating obesity phenotype and glucose and lipid metabolism, which means: using the Sdccag3 gene as a target for a drug or preparation, increasing the expression level of the Sdccag3 gene in adipose tissue, and developing a weight loss drug or preparation for regulating obesity phenotype and glucose and lipid metabolism.
4. The use according to claim 2, characterized in that The use of the Sdccag3 gene as a target for screening weight loss drugs that regulate obesity phenotypes and glucose and lipid metabolism refers to: using the Sdccag3 gene as a target for drugs or preparations, screening the drugs or preparations to find drugs or preparations that can promote the expression of the Sdccag3 gene in adipose tissue as alternative weight loss drugs or preparations for regulating obesity phenotypes and glucose and lipid metabolism.
5. The use according to claim 1, characterized in that The drugs for regulating obesity phenotype include, but are not limited to, nucleic acid molecules, carbohydrates, lipids, small molecule chemical drugs, antibody drugs, polypeptides, proteins or viruses.
6. The use according to claim 5, characterized in that The weight loss drug for regulating obesity phenotype and glucose and lipid metabolism is an Sdccag3 adipose tissue-specific overexpression adeno-associated virus vector, the effective component of which contains the nucleotide sequence shown in SEQ ID No. 1, and is specifically prepared by co-transfecting a host cell with a recombinant expression plasmid and a packaging system. The overexpression of the Sdccag3 gene inhibits the increase in blood lipid levels, reduces the size of the fat volume of obese mice, reduces the levels of serum triglycerides, cholesterol and low-density lipoprotein cholesterol in obese mice, and further reduces blood sugar, serum free fatty acids and serum insulin levels, thereby promoting glucose tolerance and insulin sensitivity.
7. The use according to claim 1, characterized in that The weight-loss drug for regulating obesity phenotype and glucose and lipid metabolism also contains a pharmaceutically acceptable excipient.
8. The use according to claim 1, characterized in that The excipient is one or more of glucose, sucrose, sorbitol, mannose, starch, microcrystalline cellulose, polyvinyl pyrrolidone, cellulose and water.
9. The use according to claim 8, characterized in that The weight-loss drug for regulating obesity phenotype and glucose and lipid metabolism is in the form of tablets, pills, powders or injections.