Application of thermogenesis-enhancing compounds to enhance thermogenesis induced by norepinephrine-like compounds in brown adipocytes

A technology of norepinephrine and brown fat, which is used in the determination/inspection of microorganisms, medical preparations containing active ingredients, drug combinations, etc., which can solve the problems of high risk of drug use, lack of effect and side effect evaluation

Active Publication Date: 2021-06-25
康建胜
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Previous research on weight-loss drugs focused on reducing energy intake, and some progress has been made. However, these weight-loss drugs lack a complete evaluation of their effects and side effects, resulting in greater risk of drug use

Method used

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  • Application of thermogenesis-enhancing compounds to enhance thermogenesis induced by norepinephrine-like compounds in brown adipocytes
  • Application of thermogenesis-enhancing compounds to enhance thermogenesis induced by norepinephrine-like compounds in brown adipocytes
  • Application of thermogenesis-enhancing compounds to enhance thermogenesis induced by norepinephrine-like compounds in brown adipocytes

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0255] Embodiment 1 ATP enhances the heat production of brown adipocytes induced by NE

[0256] If ATP wants to play a role, it must pass through the receptors on the brown fat cell membrane. The inventor detected the expression abundance of the ATP receptor (P2 receptor) in brown fat cells and found that there are multiple subtypes of ATP receptors in brown fat Among the P2X receptor subtypes, the expression of P2X1 and P2X4 is dominant; among the P2Y receptor subtypes, the expression of P2Y13 and P2Y14 is dominant, and the abundance of other subtypes is low, but they may still play an important role.

[0257] The inventors selected 10 μM ATP and the previous 0.1 μM NE to act on the cells together.

[0258] The result is as Figure 10 Shown in A-10E. ATP and NE acted together on brown adipocytes, and it was found that both ATP and ATP-γS could significantly enhance NE-induced brown adipocyte thermogenesis. The enhanced effect of ATP on NE is reflected in two aspects: one, ...

Embodiment 2

[0260] Example 2 Effect of ATP Synthase Inhibitors on NE-induced Brown Adipocyte Thermogenesis and Membrane Voltage

[0261] Rotenone (rotenone) is an electron transport chain complex I inhibitor, which blocks the transfer of electrons from NADH to CoQ. During the experiment, 5 μM rotenone was added for 30 minutes in advance, and then 0.1 μM NE was added, the results were as follows Figure 18 A-18C shown. The results showed that all cellular thermogenesis was activated, but not sustained. It shows that NADH is not necessary for the activation of thermogenesis, but it is required for the continuous thermogenesis of cells, and the proton gradient it provides is the energy source for brown adipocytes to continuously produce thermogenesis.

[0262] Oligomycin (oligomycin) is one of the inhibitors of oxidative phosphorylation. It binds to the Fo part of ATP synthase (the proton-permeable part in the membrane) and can specifically inhibit the transport of protons, so it also inhibi...

Embodiment 3

[0264] The membrane voltage change of the cell when embodiment 3NE induces

[0265] The temperature measurement method of temperature-sensitive dyes (see Chinese Patent Application No. 201410850735.3 for the method) mentions that rhodamine 800 can reflect the change of membrane voltage as a reference dye, that is, the temperature measurement method of temperature-sensitive dyes can detect temperature changes, Changes in mitochondrial membrane voltage can also be monitored simultaneously.

[0266] The result is as Figure 17 A, 17B. The results showed that the mitochondrial membrane voltage had different changes when treated with NE. Among the 150 cells in five experiments, 55.6% of the cells had decreased membrane voltage, and the decrease of membrane voltage was accompanied by the increase of cell temperature. Of these cells, 76% were thermogenic, that is, nearly 20% had increased membrane voltage and produced heat.

[0267] The results showed that the mitochondrial membra...

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Abstract

The present invention provides an application of a thermogenesis-enhancing compound to enhance the thermogenesis induced by a norepinephrine compound in brown adipocytes. Specifically, the present invention provides a use of a thermogenesis-enhancing compound for preparing a preparation or a composition. The preparation or composition is used to enhance the heat production efficiency of brown fat cells induced by NE compounds, wherein the heat production enhancing compound is selected from the group consisting of ATP compounds, ATP synthase inhibitors, or combinations thereof. The heat production enhancing compound of the present invention can significantly enhance the heat production efficiency of brown fat cells induced by norepinephrine compounds.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to a method for enhancing noradrenaline compounds to induce brown adipocyte thermogenesis and its application. Background technique [0002] For most warm-blooded animals such as birds and mammals, maintaining a constant body temperature in various complex environments requires an efficient temperature regulation system. The constant body temperature comes from the balance of heat production and heat dissipation. There are four main sources of heat in animals: basal metabolism, physical activity, thermogenesis caused by cold stimulation (including shivering thermogenesis and non-shivering thermogenesis), and the thermal effect of food. [0003] The initial heat production mechanism during cold stimulation is trembling, which generates heat through the trembling of muscle tissue, but if exposed to a cold environment for a long time, then it must rely on non-shivering heat production to ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/00A61P3/04C12Q1/02
CPCA61K45/00G01N33/5008G01N33/5044
Inventor 康建胜谢涛嵘刘春凤
Owner 康建胜
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