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Application of GPM6B gene in regulation and control of activation of brown/beige fat

A white fat, gene technology, applied in the field of genetic engineering, to achieve the effect of promoting fat loss, promoting obesity, and treating diabetes

Active Publication Date: 2021-07-27
FOURTH MILITARY MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, whether GPM6B plays a role in the activation of brown / beige fat has not been reported so far

Method used

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  • Application of GPM6B gene in regulation and control of activation of brown/beige fat
  • Application of GPM6B gene in regulation and control of activation of brown/beige fat
  • Application of GPM6B gene in regulation and control of activation of brown/beige fat

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Example 1, the expression level of GPM6B protein in brown adipose tissue is significantly lower than that in white adipose tissue:

[0037] The inguinal white adipose tissue (iWAT), epididymal white adipose tissue (eWAT) and scapular brown adipose tissue (BAT) of C57BL / 6 mice were separated under normal temperature conditions, and Western blot was used to detect the expression of GPM6B protein and brown fat-related functional protein UCP1 . like figure 1 As shown, the results showed that the expression level of GPM6B protein in brown adipose tissue was significantly lower than that in white adipose tissue. Compared with iWAT, * means P≤0.05, ** means P≤0.01; compared with eWAT, # means P≤0.05, ## means P≤0.01.

Embodiment 2

[0038] Embodiment 2, cold treatment suppressed the expression of brown / white adipose tissue GPM6B protein:

[0039]The iWAT and BAT of C57BL / 6 mice treated at 25°C and 4°C were separated, and tissue samples were collected. The expression of brown adipose tissue marker genes UCP1 and GPM6B was detected by Western blot, and the results were as follows figure 2 and image 3 as shown, figure 2 The expression changes of GPM6B and UCP1 proteins in iWAT under normal temperature and cold treatment conditions; image 3 The expression changes of GPM6B and UCP1 proteins in BAT under normal temperature and cold treatment conditions. (* stands for P≤0.05, ** stands for P≤0.01), by figure 2 and image 3 It can be seen that after cold treatment, the expression of brown fat marker gene UCP1 in iWAT and BAT increased (P≤0.01), while the expression of GPM6B decreased (P≤0.05).

Embodiment 3

[0040] Example 3, the weight reduction of mouse iWAT and BAT after knocking down GPM6B:

[0041] C57BL / 6 mice were fed high-fat for 9 weeks, and were given iWAT and BAT point injections of negative control virus (HFD-Control) and GPM6B-knockdown adenovirus (HFD-shGPM6B) for 3 weeks, respectively, and then placed at 4°C 3 days under conditions such as Figure 4 As shown, the results showed that compared with HFD-Control, the volume of iWAT and BAT in the HFD-shGPM6B group decreased, as Figure 5 As shown, the liposome ratio was significantly decreased (P≤0.05). C57 mice were fed high-fat for 9 weeks, and were given iWAT and BAT point injections of negative control virus (HFD-Control) and GPM6B-knockdown adenovirus (HFD-shGPM6B) for 3 weeks, and then placed at 4°C respectively 3 days. Compared with HFD-Control, the volume of iWAT and BAT in HFD-shGPM6B group decreased, and the ratio of liposomes decreased significantly; (* represents P≤0.05, n=8).

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Abstract

The invention discloses an application of a GPM6B gene in regulation and control of activation of brown / beige fat, and particularly, brown fat can be activated and white fat browning can be promoted by inhibiting expression of the GPM6B gene. The inhibition of the expression of the GPM6B comprises knockdown, knockout, silencing, mutation or inactivation of the GPM6B gene. The invention further discloses shRNA (short hairpin ribonucleic acid) or siRNA (small interfering Ribonucleic Acid) of the targeted GPM6B gene, wherein the nucleotide sequence of the shRNA or siRNA is shown as SEQ ID NO.11 or SEQ ID NO.12; the invention further discloses a medicine capable of treating obesity or diabetes mellitus, and the medicine contains a biological product and / or a chemical product capable of inhibiting GPM6B gene expression. The GPM6B gene disclosed by the invention can regulate and control activation of brown / beige fat, and fat reduction can be promoted and diabetes can be treated by inhibiting the function of the GPM6B gene.

Description

technical field [0001] The invention belongs to the technical field of genetic engineering, and specifically relates to the application of a GPM6B gene in regulating the activation of brown / beige fat. Background technique [0002] Obesity has become a global epidemic, which can cause damage to multiple organs, mainly manifested as cardiovascular disease and type 2 diabetes. Obesity is a chronic disease formed by excessive accumulation of white adipose tissue in the body due to the long-term energy intake of the body higher than energy consumption. Previous studies have found that there are two main types of adipose tissue in mammals, namely white adipose tissue (WAT) and brown adipose tissue (BAT). WAT stores excess energy absorbed by the body in the form of triglycerides, and the cell morphology is a single large lipid droplet with less cytoplasmic components. BAT, on the other hand, produces heat by oxidizing fatty acids, which can produce heat to maintain body temperatu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K31/7105A61K48/00A61P3/04A61P3/10C12N15/113
CPCA61K45/00A61K31/7105A61K48/005A61P3/04A61P3/10C12N15/113
Inventor 王姗陶凌张晓萌常小倩
Owner FOURTH MILITARY MEDICAL UNIVERSITY
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