CN-121971586-A - Application of polypeptide COX52-69 in reducing liver fat accumulation and reducing adipocyte volume

Abstract

One of the prior patents to which we have been entitled is cyclization of the linear peptide COX52-69 to achieve the oral route of administration. The invention discloses application of a polypeptide COX52-69 in reducing liver fat accumulation and reducing fat cell volume, which is the purpose of finding that the cyclopeptide has the effect of reducing weight. In this invention, we set up a diet-induced obesity (DIO) model by feeding C57BL/6J mice with high fat diet (45% fat-powered) for 14 weeks. After obtaining DIO mice, 17 weeks of dosing experiments using PBS buffer and Rybelsus solution as controls, it was observed that COX52-69 cyclic peptides reduced liver fat accumulation and reduced adipose tissue adipocyte volume while reducing DIO mice body weight. This suggests that the COX52-69 cyclic peptide has practical use in improving the volume of fatty liver and adipocytes.

Inventors

• LI CHENHONG
• JIANG SONGJUN

Assignees

• 中南民族大学

Dates

Publication Date

20260505

Application Date

20251208

Claims (4)

1. 1. Use of the cyclic peptide COX52-69 in the manufacture of a medicament for ameliorating or preventing fatty liver.
2. 2. Use of the cyclic peptide COX52-69 in the manufacture of a medicament for reducing adipocyte volume.
3. 3. Use according to claims 1 and 2, characterized in that the corresponding linear peptide COX52-69 of the cyclic peptide COX52-69 has the same application.
4. 4. Use according to claims 1, 2 and 3, characterized in that the polypeptide COX52-69 is used for improving some metabolic indicators in obese subjects.

Description

Application of polypeptide COX52-69 in reducing liver fat accumulation and reducing adipocyte volume Technical Field The invention belongs to the field of biological medicine, and in particular relates to an application of a polypeptide in improving fatty liver and reducing the volume of fat cells. Background The short peptide COX52-69 is a polypeptide containing 18 amino acids, which was originally isolated and purified from the small intestine of swine, and was found to overlap completely with the 52 th to 69 th of cytochrome oxidase VIII after amino acid sequence alignment, so we named COX52-69. The sequence is LLPAGWVLSHLDSYKKRE. The isolated COX52-69 polypeptide has been found to inhibit secretion of glucose-mediated insulin by a work function test, which was issued in 2018 by Chinese patent application No. CN 201310471571.9. The bioactive short peptide COX52-69 is obtained by solid phase synthesis. However, it can only exert its efficacy by injection administration, but cannot exert its effect by oral administration. Therefore, the polypeptide is modified to realize oral administration, chinese patent application No. CN 202110380196.1 is obtained in 2022, and the amino acid sequence of the modified peptide is C. LLPAGWV- [ N-Me-Leu ] -SHLDSYKKREC. Recently we have found that the COX52-69 cyclic peptide reduces liver fat accumulation and adipocyte volume while reducing body weight in DIO mice. This suggests that the COX52-69 cyclic peptide has practical use in improving the volume of fatty liver and adipocytes, Disclosure of Invention The present invention is the use of our patented cyclic peptide COX52-69 to improve the volume of fatty liver and adipocytes. We utilized a high-fat diet-induced obese mouse model (DIO model), which is a commonly accepted model for modeling human obesity and its associated metabolic syndrome, and found through rigorous experimentation that COX52-69 cyclic peptides improved glucose and insulin resistance in mice, exhibited clear metabolic improvement effects, significantly reduced liver fat accumulation, improved fatty liver symptoms, and reduced epididymal fat cell volume. Indicating its potential for regulating sugar metabolism and improving insulin sensitivity. Drawings FIG. 1 shows COX52-69 cyclic peptides reducing liver lipid accumulation by H & E stained liver tissue sections, with the horizontal representing the same feed and the vertical representing the same dosing treatment. The figure shows that the liver tissue of the mice in the common feed group has clear substantial structure, liver cells are radially arranged, cytoplasm is uniformly dyed, obvious cavitation-like fat deposition is avoided, large-area steatosis or inflammatory infiltration is not seen, and the intervention drug has no obvious adverse effect on the structure of the liver tissue. The sections of the Model group showed a large number of lipid vacuoles and hepatocytes were deformed by compression and even exhibited a "net" structure. Denatured hepatocytes and lipid droplets left empty in the Rybelsus and COX groups of liver tissue sections were also seen, but various improvements over the Model group were seen. Figure 2 shows the effect of COX52-69 cyclic peptides on adipose tissue, with the fat tissue sections of epididymis stained with oil red O shown in panel a (< 0.0001) for comparison with Model group, with the transverse direction representing the same feed and the longitudinal direction representing the same treatment. The Control group had a uniform adipocyte size and a more regular distribution, while the Ryb-Control group and the COX-Control group showed adipose tissue morphology under the administration treatment, which was substantially similar to the Control group. While the adipose tissue cell area of the Model group is significantly larger than that of the two administration groups, the cell arrangement form is compact, and the adipose cell area of the two administration groups is significantly smaller than that of the Model group. Panel b shows the cell area under the section of each group of adipocytes, and the difference between the Control group and the Model group is significant (P < 0.0001) after statistics, while the area of adipocytes is significantly reduced (P < 0.0001) in the two administration groups, indicating that COX52-69 cyclic peptides reduce the volume of adipocytes to some extent, thereby also alleviating fat accumulation. Detailed Description 1. Construction of high-fat diet-induced mouse obesity model There are various modeling methods to obtain an obesity model of mice, we selected 6 week old male C57BL/6J mice for DIO modeling, after one week of adaptive feeding, the mice were randomly divided into ND group and HFD group, and Normal Diet (ND) and High Fat Diet (HFD) were administered separately, using 45% fat-powered high fat diet of model D12451 to simulate human obesity. Mice were weighed weekly, grouped after 14 weeks, and then given by gavage, sacrificed