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Use of wdr6 in lowering triglyceride levels

A technology of triglyceride levels and uses, applied in the field of biopharmaceuticals, to achieve the effect of reducing triglyceride levels and improving triglyceride metabolism disorders

Active Publication Date: 2021-09-17
SHANDONG PROVINCIAL HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] WDR6 is a protein containing the WD repeat functional domain. At present, there are few studies on this protein, especially in the environment of hyperlipidemia, the regulation of WDR6 on AMP-dependent protein kinase (AMP activated protein kinase, AMPK), and the regulation of lipid There is no relevant report on the influence of quality metabolism

Method used

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  • Use of wdr6 in lowering triglyceride levels
  • Use of wdr6 in lowering triglyceride levels
  • Use of wdr6 in lowering triglyceride levels

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Example 1. Hyperlipidemia leads to an increase in animal liver WDR6 levels

[0039] The level of WDR6 was evaluated in the high-fat animal model, and the specific experimental process was as follows:

[0040] 1. Construction of high-fat animal model

[0041]The wild-type mice were fed with a normal diet until 8 weeks old, and divided into two groups, one group was a high-fat model group, which was fed with a high-fat diet (60% kJ fat, D12492, Research diets, New Brunswick, NJ, USA); The other group was the control group, which maintained a normal diet. The feeding conditions of the two groups of mice are as follows: 12h / 12h light-dark cycle per day, 50% humidity, 22-24°C, free access to food and water.

[0042] 2. Protein level assessment of liver WDR6 and related lipid metabolism signaling pathways

[0043] The two groups of mice in step 1 were fed for 16 weeks and fasted for 12 hours. For the samples used for expression level analysis, the liver tissues were washed...

Embodiment 2

[0052] Example 2. Deletion of WDR6 can improve triglyceride deposition in mouse liver primary cells under high-fat conditions

[0053] The liver primary cells of wild-type mice and WDR6-KO mice were isolated, and the cells were sliced, and then treated with 0.2mM palmitic acid (palmitic acid stimulated to simulate a high-fat environment) and serum albumin (BSA) (control) for 24 hours. Hour. Oil red staining (analysis of triglyceride (i.e. fat) or lipid accumulation level) on the treated cells, the results are as follows figure 2 shown.

[0054] The above oil red staining method is as follows:

[0055] Fix the treated cell slides in paraformaldehyde for 15-30 minutes, wash off the fixative with tap water (5 minutes, 3 times), then stain with oil red staining solution for 8-10 minutes in the dark, and differentiate with 40% ethanol. Soak in distilled water, counterstain with hematoxylin for 2-3 minutes, wash in tap water until the water does not change color, then differenti...

Embodiment 3

[0057] Example 3. Palmitic acid stimulates human liver cell lines and evaluates the level of WDR6

[0058] The HepG2 cell line was cultured in 6-well plates and cell slides to exponential growth phase, replaced with serum-free DMEM medium, starved for 12 hours, and then added 0.4mM palmitic acid (palmitic acid stimulated to simulate a high-fat environment) and an equal amount of serum white Cells were treated with protein (BSA) (control), oil red staining was performed to analyze the triglyceride level and Western Blot was used to analyze the protein level of WDR6, the results were as follows image 3 shown.

[0059] The above oil red staining method is as follows:

[0060] Collect the cells treated for 12 hours, fix the cell slides in paraformaldehyde for 15-30 minutes, wash off the fixative with tap water (5 minutes, 3 times), and then stain with oil red staining solution for 8-10 minutes in the dark, 40 Differentiate with % ethanol, soak in distilled water, counterstain w...

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Abstract

The present application discloses the use of WDR6 in reducing triglyceride levels. The use is specifically the use of the agent for inhibiting WDR6 activity in the preparation of a product for reducing triglyceride levels in a subject. The study of this application found that WDR6 can affect the mature level of the key transcription regulator SREBP1c in the triglyceride synthesis pathway by regulating the phosphorylation level of AMPK, thereby regulating the triglyceride synthesis pathway, and inhibiting WDR6 can improve triglyceride synthesis The role of pathways. This method can significantly improve the lipid metabolism disorder in a high-fat diet environment than in a normal diet or a physiological environment. The invention provides a new approach for improving metabolic disorder under high-fat diet environment and preparing products for lowering triglyceride levels in subjects.

Description

technical field [0001] The invention relates to the field of biopharmaceuticals, in particular to the use of lipid metabolism molecule WDR6 in reducing triglyceride levels. Background technique [0002] Disorders of lipid metabolism can cause ectopic deposition of lipids in the body, leading to lipotoxicity. Excess lipids may accumulate in the liver, blood vessels, myocardium, thyroid and other tissues and organs, affecting normal physiological functions. Therefore, high fat is a risk factor for fatty liver, liver disease, atherosclerosis, coronary heart disease, and thyroid disease. High fat makes the incidence of fatty liver, coronary heart disease, atherosclerosis and other diseases in patients with hypertriglyceridemia and mixed hyperlipidemia higher than that of normal people. [0003] The liver is a key organ for fat metabolism, and most of the de novo synthesis, transport and oxidative metabolism of triglycerides (i.e. fat) occur in the liver. Therefore, excessive ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/00A61K31/7088A61P3/06
CPCA61K31/7088A61K45/00A61P3/06
Inventor 薄涛高聆宫颖
Owner SHANDONG PROVINCIAL HOSPITAL
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