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Application of P110 alpha in preparation of reagent for regulating and controlling animal energy metabolism

A technology of energy metabolism and reagents, applied in the application field of reagents, can solve problems that have not been studied clearly

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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

In addition, CNP2 may have special physiological functions in peripheral tissues, but it has not been studied clearly

Method used

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  • Application of P110 alpha in preparation of reagent for regulating and controlling animal energy metabolism
  • Application of P110 alpha in preparation of reagent for regulating and controlling animal energy metabolism
  • Application of P110 alpha in preparation of reagent for regulating and controlling animal energy metabolism

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Embodiment 1

[0036] The acquisition of embodiment 1 transgenic mice

[0037] 1. Source of experimental animals in the present invention: P110α flox / flox , P110β flox / flox Introduced from Harvard Medical School (Department of Cancer Biology, Dana-Farber Cancer Institute and Departments of Pathology and Surgery, Harvard Medical School, Boston, MA 02115, USA); Cnp-Cre + / - Mice were imported from Germany (Department of Neurogenetics, Max planck Institute of Experimental Medicine, D-37075 Goettingen, Germany); Ai9 mice were imported from Allen Institute for Brain Science, Seattle, WA 98103, USA. These mice were all of the C57BL / 6 strain. Part of the animal models or experimental methods involved in this application can be operated by referring to the relevant master's thesis "The Effect of PI3K Pathway on Myelin Sheath and Body Weight of Mice—CNP-cre:P110αflox / flox Mice Phenotype Analysis" by the inventor's research group , the present application continues further detailed research on the b...

Embodiment 2

[0058] Example 2 Discussion on Abnormal Energy Metabolism in P110αCKO Mice

[0059] 1. P110αCKO mice have a tendency to brown WAT

[0060] WAT (white adipose tissue) can secrete various adipokines such as leptin and adiponectin, and regulate the energy metabolism of the body in autocrine, paracrine and endocrine ways. Under certain conditions, WAT will brown, and brown-like fat cells will appear, which will increase the energy consumption of the body through metabolic heat production, which is conducive to weight loss. Because capillaries in local WAT of P110αCKO mice were significantly increased, which is one of the characteristics of browning of WAT, we guessed that browning of WAT in these parts may have occurred. To confirm this point, we detected the expression of brown fat marker protein Ucp1 mRNA in the groin, perigonadal and postrenal WAT of 120-day-old P110αCKO and control mice by RT-qPCR ( Figure 7 ). The results showed that, compared with the control group, the ...

Embodiment 3

[0070] Example 3 Discussion on Peripheral Tissues of P110αCKO Mice

[0071] 1. Discussion on gene knockout in peripheral tissues of P110αCKO mice

[0072] Liver, skeletal muscle and WAT are important peripheral energy metabolism organs in the body. We observed that Cnp-Cre + / - The liver of / Ai9 gene reporter mice showed obvious redness after perfusion, and microscopic observation showed that tdTomato protein was highly expressed in the liver ( Figure 13 A). We speculate that P110α is knocked out in the liver of P110α CKO mice. At the same time, we also found that the gene reporter expressed a small amount in the skeletal muscle of the mouse, and there was very little or no expression of tdTomato protein in the groin WAT ( Figure 13 A). Therefore, we focused our research on the liver.

[0073] From the results of morphological studies, P110α may be knocked out in the liver of P110α CKO mice. To further confirm this point, we extracted the livers of 180-day-old P110αCKO...

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Abstract

The invention belongs to the technical field of biology, and particularly relates to application of P110 alpha in preparation of a reagent for regulating and controlling animal energy metabolism. The research finds that the weight of a P110 alpha CKO mouse is reduced. The mouse P110 alpha gene is massively knocked out in the liver and is mainly knocked out in liver sinus endothelial cells (LSECs), and meanwhile, CNP is prompted to be massively expressed in the liver and is mainly expressed in the LSECs. The up-regulation of FGF21 in LSECs of the P110 alpha CKO mouse causes the increase of the FGF21 protein expression of the liver and the FGF21 level of serum, which is possibly caused by the weakening of the synthesis of the liver and white fat (WAT), the enhancement of fatty acid-beta oxidation, the increase of the energy consumption of the body and the weight loss.

Description

technical field [0001] The invention belongs to the field of biotechnology, and particularly relates to the application of P110α in the preparation of reagents for regulating animal energy metabolism. Background technique [0002] Energy balance is very important for body homeostasis. When energy intake exceeds energy expenditure for a long time, obesity is caused. Obesity is a global epidemic and a high risk factor for cardiovascular disease, type 2 diabetes, certain cancers, and musculoskeletal diseases. Because of its complex pathogenesis, there is currently no effective treatment. Energy balance is regulated by the central nervous system (CNS) and peripheral tissues, among which the hypothalamus is an important center for regulating energy metabolism, and the liver is one of the most important peripheral metabolic organs of the body. [0003] CNP is one of the most abundantly expressed proteins in the mammalian CNS. In the human CNS, CNP is mainly expressed in the non-...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61P3/04
CPCA61K45/00A61P3/04
Inventor 符辉常连生
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