Application of estrogen

A technology for estrogen and insulin resistance, applied in the field of medicine and biology, can solve the problems of limited prevention and treatment methods and unclear mechanism, and achieve the effect of inhibiting hepatic triglyceride synthesis and improving fatty liver and insulin resistance.

Inactive Publication Date: 2013-04-24
SHANGHAI INST FOR ENDOCRINE & METABOLIC DISEASES
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  • Description
  • Claims
  • Application Information

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Problems solved by technology

Studies have shown that NAFLD is closely related to obesity and insulin resistance, but its

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  • Application of estrogen
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Experimental program
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Embodiment 1

[0028] In order to study the role of estrogen in liver glucose and lipid metabolism, especially in the occurrence and development of NAFLD, we analyzed the incidence of NAFLD among women in the population, and the results are shown in Table 1.

[0029]A total of 808 subjects were included in the study, divided into premenopausal and postmenopausal groups, and B-ultrasound was used as the diagnostic method for NAFLD. There were 280 premenopausal women and 528 postmenopausal women, and the average ages were 45.3±4.1 and 56.8±4.7 years. Analysis of the data shows that the BMI and waist-to-hip ratio of the latter are significantly higher than those of the former, suggesting that postmenopausal women have more serious metabolic disorders than premenopausal women. The incidence of NAFLD was also significantly different between the two groups, starting from 42.9% in the premenopausal group, and as high as 60.2% in the postmenopausal group, which was significantly higher than the form...

Embodiment 2

[0033] Embodiment 2 mouse model

[0034] (1) Study on the effect of tamoxifen on hepatic triglyceride metabolism

[0035] In order to further verify the effect of estrogen on the occurrence and development of NAFLD, the mouse model was used to conduct animal level research.

[0036] Tamoxifen, as an estrogen inhibitor, is clinically used in the treatment of breast cancer. However, population studies have found that patients who use tamoxifen often develop non-alcoholic fatty liver, which has become one of its main side effects. In the mice treated with moxifen, the liver and serum triglyceride levels were increased, which was consistent with the literature reports. Gene expression analysis found that the expression of FASN and ACC1 increased, suggesting that tamoxifen may promote the occurrence of fatty liver by affecting triglyceride synthesis.

[0037] In order to test the effect of tamoxifen on lipid metabolism, female C57 mice were treated with tamoxifen (1 mg / kg / d) for ...

Embodiment 3

[0044] Example 3 Effect of estrogen on improving glucose and lipid metabolism in obese mice induced by high fat (HFD).

[0045] High-fat-fed mice are a mouse model of obesity, insulin resistance, and impaired glucose tolerance. By giving high-fat-fed male mice estrogen (50ug / kg / d) for two weeks, significant metabolic Phenotypic changes, insulin sensitivity, glucose tolerance, and hepatic triglyceride deposition were all significantly improved. While estrogen reduced hepatic triglyceride deposition, it was found that serum triglycerides did not decrease in estrogen-treated mice. At the same time, a significant reduction in subcutaneous fat was found in the estrogen-treated mice. Since adipose tissue is also an important organ affecting serum triglycerides, we believe that the inconsistency between serum triglycerides and liver triglycerides changes may be due to the widespread effects of estrogen.

[0046] We found that estrogen significantly reduced liver triglycerides in hi...

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Abstract

The invention belongs to the field of pharmaceutical biology. The estrogen plays an important role in the liver glucolipid metabolism process, has a protection effect to livers and can be used for preparing medicines for treating fatty liver and particularly non-alcoholic fatty liver diseases. A receptor regulated by the estrogen is an SHP (Small Heterodimer Partner) gene, and by adjusting the expression of the liver SHP gene, the synthesis of liver triglyceride and fatty acid is inhibited, and the function of alleviating the fatty liver is brought into play. According to the invention, a specific target is provided for screening a medicine for treating fatty liver, the regulation effect of the estrogen to SHP gene is confirmed, and the relevant relationship between the regulation effect and the NAFLD (Non-Alcoholic Fatty Liver Disease) provides reliable basis and indexes for researching the prevention and treating target points of the fatty liver; and furthermore, from the aspect of endocrine regulation, a new way is provided for preventing and treating glycolipid metabolic diseases.

Description

technical field [0001] The invention relates to the field of medical biology, specifically the application of estrogen in the preparation of drugs for treating fatty liver and the drug for regulating SHP gene, and the application of SHP gene in the preparation of drugs for treating fatty liver Background technique [0002] With the improvement of people's living standards, non-alcoholic fatty liver disease (NAFLD) has become an increasingly serious health problem, and its prevalence in developed countries is close to 30%, becoming the leading cause of chronic liver disease. When the balance of lipid metabolism in the body is disturbed, excessive triglycerides will accumulate in the liver cells in the form of lipid droplets, which will cause fatty changes in the liver cells and the formation of NAFLD. Studies have shown that NAFLD is closely related to obesity and insulin resistance, but its mechanism is not yet clear, and the prevention and treatment methods are even more li...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K48/00A61K49/00A61P1/16A61P5/50
Inventor 宁光王晓琳李小英王计秋陆炎
Owner SHANGHAI INST FOR ENDOCRINE & METABOLIC DISEASES
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