Use of glycerol kinase in preparation of drug for regulating lipid metabolism

A technology of glycerol kinase and hypertriglyceridemia, which is applied in the field of medicine and can solve the problem of no glycerol kinase and the like

Active Publication Date: 2018-05-08
SHANGHAI INST OF BIOLOGICAL SCI CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] In the prior art, there is no report about the role of glycerol kinase in fatty liver and hypertriglyceridemia, and the regulation of hepatic fatty acid and triglyceride synthesis by regulating the expression of SREBP-1c to maintain blood lipid homeostasis

Method used

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  • Use of glycerol kinase in preparation of drug for regulating lipid metabolism
  • Use of glycerol kinase in preparation of drug for regulating lipid metabolism
  • Use of glycerol kinase in preparation of drug for regulating lipid metabolism

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0098] Example 1. The expression of glycerol kinase in the liver of mice with lipid metabolism disorder induced by high-fat diet is increased, and inhibiting the expression of glycerol kinase can significantly alleviate fatty liver and improve hyperlipidemia

[0099] Glycerol kinase participates in triglyceride synthesis by catalyzing glycerol to 3-phosphoglycerol, and regulates hepatic fatty acid and triglyceride synthesis by regulating the expression of lipid synthesis-related enzymes mediated by SREBP-1c. Glycerol kinase is mainly expressed in the liver.

[0100] The inventors established mouse fatty liver and hyperlipidemia models through a high-fat diet. It was found that the mRNA and protein levels of glycerol kinase (Gyk) in the liver of C57BL / 6 mice fed with high fat diet (HFD) for 3 months were significantly higher than those of mice fed with conventional diet in the control group ( figure 1 A).

[0101] The present inventor suppresses the liver Gyk expression ( fi...

Embodiment 2

[0103] Example 2. Glycerol kinase regulates liver lipid metabolism and blood lipid homeostasis by regulating glycerol metabolism and SREBP-1c-mediated regulation of lipid metabolism-related enzyme expression

[0104] The inventors explored the function and mechanism of Gyk in liver lipid metabolism and blood lipid homeostasis in normal mice.

[0105] First of all, the inventors observed the effect of overexpressing Gyk on the lipid metabolism of mice by using an adenovirus expression system, and found that Gyk was overexpressed ( figure 2 A) It does not affect the body weight and body fat content of mice, but the serum glycerol level of Gyk overexpressed mice is significantly reduced ( figure 2 B), liver triglyceride (TG) content ( figure 2 C), serum TG level ( figure 2 D) and free fatty acid (FFA) levels ( figure 2 E) are significantly higher than the control mice. These results suggest that Gyk may regulate fatty acid metabolism in addition to regulating liver and b...

Embodiment 3

[0108] Example 3, Gyk regulates the molecular mechanism of liver lipid metabolism

[0109] Further, the inventors explored the molecular mechanism of Gyk regulating liver lipid metabolism, and found that the overexpression of Gyk in normal mice through adenovirus mediated significantly increased the mRNA levels of various enzymes in the hepatic fatty acid synthesis and triglyceride synthesis pathways ( image 3 A), including fatty acid synthase (FASN), ATP-citrate lyase (ACL), acetyl-CoA carboxylase 1 (ACC1), diacylglycerol acyltransferase (DGAT2), and glycerol-3-phosphate acyltransferase Enzyme (GPAT2). In contrast, the mRNA expression of these enzyme genes was significantly decreased in the liver of Gyk knockout mice ( image 3 C). SREBP-1c is a key transcription factor regulating the expression of these liposynthase genes. The inventors found that the mRNA level of SREBP-1c was significantly increased in Gyk overexpression mouse liver ( image 3 B), in the liver of Gyk k...

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Abstract

The invention relates to a use of glycerol kinase in preparation of a drug for regulating lipid metabolism. The use reveals that glycerol kinase can catalyze glycerol into 3-phosphoglycerol for triglyceride synthesis, control the expression of SREBP-1c to adjust and control hepatic fatty acid and triglyceride synthesis and play an important role in maintenance of the blood lipid homeostasis. The lipid metabolism disorder mouse model has high glycerol kinase expression and thus through inhibiting the expression of glycerol kinase, the drug can significantly improve high fat food-induced fatty liver and hypertriglyceridemia. Therefore, glycerol kinase is a new target for preventing, alleviating or treating fatty liver and hypertriglyceridemia.

Description

technical field [0001] The invention belongs to the field of medicine, and more specifically, the invention relates to the application of glycerol kinase in the preparation of drugs for regulating lipid metabolism. Background technique [0002] Fatty liver refers to the pathological changes caused by excessive accumulation of fat in liver cells due to various reasons. Fatty liver disease is seriously threatening the health of Chinese people, becoming the second major liver disease after viral hepatitis. Fatty liver can be divided into alcoholic fatty liver and non-alcoholic fatty liver. Alcoholic fatty liver disease is caused by long-term, excessive drinking. Non-alcoholic fatty liver is mainly caused by high-fat diet, obesity, diabetes, etc. Generally speaking, early fatty liver is a reversible disease, early diagnosis and timely treatment can often return to normal. The clinical manifestations of fatty liver are various, and mild fatty liver has no clinical symptoms. ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/48C12N15/861A61K45/00A61K48/00A61K31/7088A61P1/16A61P3/06
CPCA61K31/7088A61K45/00C12N15/86C12N2710/10043C12Q1/485G01N2333/91215
Inventor 乐颖影卓鉥
Owner SHANGHAI INST OF BIOLOGICAL SCI CHINESE ACAD OF SCI
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