CN106349356A - Protein with irisin functional structure and application thereof - Google Patents
Protein with irisin functional structure and application thereof Download PDFInfo
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- CN106349356A CN106349356A CN201610782021.2A CN201610782021A CN106349356A CN 106349356 A CN106349356 A CN 106349356A CN 201610782021 A CN201610782021 A CN 201610782021A CN 106349356 A CN106349356 A CN 106349356A
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- irisin
- albumen
- compositionss
- functional structure
- protein
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- 239000007921 spray Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- DCXXMTOCNZCJGO-UHFFFAOYSA-N tristearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 230000037303 wrinkles Effects 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Abstract
The invention relates to protein with an irisin functional structure and application thereof, and belongs to the technical field of biological medicines. The amino acid sequence of the protein provided by the invention is as shown in SEQ ID NO:1. The protein provided by the invention has a key conserved structure and physiological functions similar to those of natural irisin, can be used as an efficient irisin supplementing agent, is small in molecular weight, and has the advantages of being easily absorbed through injection, oral taking and subcutaneous permeation; and the protein has characteristics similar to those of an irisin structural domain, white fat in a body can be converted into brown fat, energy consumption and immunological enhancement can be achieved, and thus a novel effective way is provided for preventing or treating diseases or states caused by excessive energy intake/storage.
Description
Technical field
The present invention relates to a kind of multifunctional protein and its application are and in particular to a kind of albumen with irisin functional structure
And its application.
Background technology
Irisin (irisin) be a kind of by bostrom and colleague 2012 separation obtain containing 112 aminoacid
The albumen of residue, its molecular weight is about 12kda.Bostrom statement irisin is a kind of glycoprotein, and physiologically active state is subject to not
With the glycosylated impact of degree.Irisin is a kind of agnoprotein cleavage type fibronectin domains albumen in human muscular tissue
The product of 5 (fndc5).Fndc5 is then a kind of vivo protein finding in 2002, and Mus source fndc5 contains three parts: 29 amino
The signal peptide of sour residue composition；The type fibronectin domains of 94 amino acid residues and a c end.The fndc5 of cross-film is than trip
Bigger from fndc5, about 32kda.Irisin is the c terminal cleavage product of fndc5, and this product is in mammalian body inner height
Conservative.
The cutting release of irisin is cut with the transmembrane polypeptide such as epidermal growth factor (egf), transforming growth factor α (tgf)
Cut release process to be similar to.The expression of fndc5 is subject to peroxisome proliferation activity factor y (ppary) and coactivator α
The stimulation of (pgc1 α) and increase.In muscle cell synthesize five kinds of secreting type factors related to pgc1 α, that is, fndc5, il-15,
Vegf β, lrg1 and timp4.And pgc1 α participates in the energy metabolism in the biological transcription of regulation and control and Intramitochondrial oxidation generation
Thank and energy production.Research finds, muscle secretion pgc-1 α, the downstream elements shearing of this protein regulation and the modification after exercise
Fndc5 forms irisin.
Fat, it has also become Modern Public Health problem.Obesity causes mainly due to body white accumulation of fat, mammal
Internal white adipose tissue stores most fatty acids and triacylglycerol, and does not almost have structure of mitochondria.White
Fatty tissue also take part in the Development Process of insulin resistant.Except storing up fat, white adipose tissue also synthesizes and secretes one
A little small-molecule substances, such as leptin (leptin), hungry element (ghrelin), new fats factor of n ucb2/nesfatin-1 and kite
Tail element (irisin), is one of endocrine organ main in vivo.Harvard University medical college cytobiology professor Bu Lu
With the mouse that seldom moves as experimental subject, these mouse overweights have prediabeteses disease to this Spiefelman simultaneously
Shape, Spiefelman finds, after these mouse accept irisin injection, the fatty gene to brown fat conversion of body white is such as
Elov13, cox7a and otop1 etc. are activated.Brown adipose tissue after conversion prevents distributing by quick consumption of glucose and fat
Heat, and consume the white adipose of storage further.Compared with white adipose tissue, in brown adipose tissue, contain substantial amounts of fat
Grain and mitochondrion, specific play a role in energy consuming process.Contain on mitochondrial inner membrane in brown adipose tissue
A kind of albumen being referred to as Uncoupling pro-tein-2 (ucp-1), proton can be pumped into mitochondrion base from subintimal space by these albumen
In matter.When ucp-1 is activated, Intramitochondrial metabolic response no longer will produce atp, but directly produce heat.Research display,
20nm fndc5 is i.e. so that the mrna expression of ucp1 improves 7-1500 times.Irisin average level in male's body is
353.1 ± 18.6ng/ml, in women body, average level is 267.6 ± 12ng/ml, and the irisin in obesity patient's body
Average level is 198.4 ± 7.8ng/ml.Reduce with body weight, internal irisin level also can decrease, therefore irisin
It is also considered as the cue mark of body fat content.
More than that, it can also improve the glucose tolerance of high fat diet mouse to the effect of irisin.Injection Rhizoma Iridis Tectori
After element, the blood glucose of mouse and insulin level are improved, and this can stop diabetes onset, and inject irisin do not occur any
Side effect.
Irisin can also strengthen heart and immunologic function, for example, produce antiphlogistic effects.And improve god by trophic factors
Through meta function and structure, senile and organic function of nervous system degenerative process plays the effect maintaining function.
In addition, aging course is closely related with nutritive equilibrium, gentle energy (calorie) is taken in restriction and is had been demonstrated energy
Enough extend mammalian longevity.Current research in 2014 display irisin can send out in vivo to Energy intaking limit similar
Effect, that is, pass through to increase energy expenditure, reduce the energy accumulation of body white fatty tissue, slow down telomere simultaneously and shorten speed,
Thus slowing down senility of humanbody.
In general, current research thinks that irisin is being treated obesity, improved neuronal function and structure, hypermnesis
All have a good application prospect with delaying senility aspect.But at present, at home and abroad there is no restructuring irisin or its functional structure
Analog is as the application of efficient irisin supplement in vivo.
Content of the invention
It is an object of the invention to provide in place of overcoming the deficiencies in the prior art a kind of there is irisin functional structure
Albumen and the polynucleotide encoding this albumen.
Another object of the present invention is to providing a kind of compositionss containing above-mentioned albumen and the application of this albumen.
For achieving the above object, the technical scheme that the present invention takes is: a kind of albumen with irisin functional structure, its
Aminoacid sequence is as shown in seq id no:1.
Above-mentioned albumen is a kind of albumen with irisin domain similar functions, and it shows greater activity and stablizes
Property.Inventor utilizes analysis program, according to the homology of the albumen to the people present invention for the default parameterss and the irisin of art technology
Property carries out sequence alignment analysis, and result show that the albumen of the present invention is similar with irisin function conserved domain sequence, specifically,
It has the sequence similarity with natural hormone irisin (irisin) 67% in human body, before irisin and its vivo excision
The crucial conserved functional domains of build fibronectin domains albumen 5 (fndc5).
Above-mentioned albumen can be obtained by heterologous recombination expression well known by persons skilled in the art, for example, the present invention's
Albumen can in Pichia sp. the corresponding preference codon gene of its sequence of heterogenous expression, and concentrate according to affinity chromatograph mode
Separate.Typically, these methods include adding his label (his-tag) to native protein c end.Typically, the restructuring that the method obtains
Albumen there occurs glycosylation modified, and the glycosylation modified similar in form with people source.By adjusting heterogenous expression condition, may change
Recombiant protein level of glycosylation.
Meanwhile, present invention also offers another has the albumen of irisin functional structure, it is following (a) or (b):
(a) as shown in seq id no:1 aminoacid sequence through modification obtained by with above-mentioned albumen, there are identical functions
Protein derivatives；
(b) as shown in seq id no:1 aminoacid sequence through one or more amino acid residues replacement, lack or add
Plus obtained above-mentioned albumen has the protein derivatives of identical functions.
Furthermore, the invention provides a kind of above-mentioned polynucleotide stating the albumen with irisin functional structure of coding.This
Field those of ordinary skill is it is known that can determine coding as shown in seq id no.1 according to the corresponding codon of different aminoacids
The polynucleotide of the polypeptide of albumen.Due to the degeneracy of codon, described polynucleotide can have different forms, preferably root
According to the usage frequency of different biometrics password, select corresponding codon.The polynucleotide sequence of the polypeptide of the present invention can be
Dna or rna, wherein dna include the dna of cdna, genome dna and synthesis, and dna can be double-strand or single stranded form, single
Chain dna can be coding strand or noncoding strand (antisense strand).
Additionally, a kind of the invention provides compositionss containing the such as above-mentioned albumen with irisin functional structure.This
The bright albumen with irisin functional structure can cause for preventing or treating because irisin lacks as active component
Disease or state compositionss in.In the present invention, term " irisin lacks and the disease that causes or state " refer to due to
Internal irisin is not enough or natural shortage causes the change of the signal path of correlation and the physiological reaction that leads to.Preferably, may be used
The albumen of the present invention or compositionss to be focused on prevention or the activity of therapeutic efficiency is described as: improve the health care of sleep, reduce fat, delay
Old and feeble.It is highly preferred that the compositionss of the present invention show effect of protection telomere.Especially since its low-molecular-weight, at this
The albumen being used as active component in bright compositionss shows excellent percutaneous permeability.Therefore, when the compositionss office of the present invention
When portion is applied to skin, skin aging state significantly improves, and most preferably improves wrinkle or skin elasticity, prevention skin aging.
As the preferred implementation of compositionss of the present invention, described compositionss are pharmaceutical composition, cosmetic combinations
Thing or Halth-care composition.
As the preferred implementation of compositionss of the present invention, described compositionss are pharmaceutical composition, described medicine group
Compound also comprises pharmaceutical carrier.Wherein, pharmaceutical carrier is commonly used in pharmaceutical formulation.The albumen of the present invention is in pharmaceutical composition
Content is medicinal effective dose, and medicinal effective dose refers to albumen efficiency and active amount enough to show and realize the present invention.
As the preferred implementation of compositionss of the present invention, described pharmaceutical carrier comprise Lactose, dextrose, sucrose,
At least one in Sorbitol, Mannitol, starch.As the preferred implementation of compositionss of the present invention, described medicine group
Compound also comprises lubricant, wetting agent, sweetener, fumet, emulsifying agent, suspending agent and preservative.Those skilled in the art can
According to routine techniquess, the albumen of the present invention is prepared together with pharmaceutical acceptable carrier as above and/or excipient, according to this
Bright described pharmaceutical composition, finally provides single-dose type and the multiple dose type of several forms.
As the preferred implementation of compositionss of the present invention, when described compositionss are cosmetic composition, describedization
Cosmetic compositions also comprise adjuvant；When described compositionss are Halth-care composition, described Halth-care composition also comprises health product
Use carrier.
When described compositionss are cosmetic composition, the albumen of present invention content in the composition is beauty treatment effective dose,
Wherein, beauty treatment effective dose refers to the amount enough to realize above-described effect improving skin condition.We can be by the present invention
Cosmetic composition make a variety of forms, it may for example comprise solution, suspension, emulsion, cream, ointment, gel, frost, wash
Agent, powder, soap, the cleaning agent containing surfactant, oil, foundation cream, emulsion foundation cream, wax foundation and spray.Specifically,
Can be so that the cosmetic composition of the present invention to be made following form: nutritional solution, nourishing cream, massage cream, essence, eye cream etc..
Finally, present invention also offers the above-mentioned albumen with irisin functional structure or above-mentioned composition are in preparation treatment
Obesity drug, antiaging agent, the application improving in memory medicine or anti-aging cosmetics.The albumen of the present invention or compositionss
Gene such as elov13, cox7a and the otop1 etc. promoting white adipose to convert in vivo can be activated to brown fat, after conversion
Brown adipose tissue is by quick consumption of glucose and the anti-scattered caloric value of fat, and consumes the white adipose of storage further.Thus
Effectively reduce internal triglyceride (tg) content, reduce body weight purpose, therefore can be used for preparing obesity treating medicine.This
The albumen of invention or compositionss can increase energy expenditure, reduce body white Fat Accumulation, gently limit energy (calorie)
Take in, slow down telomere simultaneously and shorten speed, thus slowing down senility of humanbody, therefore can be used for preparing antiaging agent, cosmetics or
Health product.The albumen of the present invention or compositionss can strengthen heart and immunologic function, and improve neural elementary work by trophic factors
Energy and structure, play, in senile and organic function of nervous system degenerative process, the effect maintaining function, can be used for preparation and improve
In the medicine of memory or health product.
Compared with prior art, the invention has the benefit that the albumen of the present invention has the similar pass of natural irisin
Key conserved structure and physiological function, can be little as a kind of efficient irisin supplement, molecular weight, have be easy to by injection,
It is administered orally and the absorbed advantage of subcutaneous osmotic.
Albumen provided by the present invention is the brand-new albumen of a class, and its structure is simple, it is convenient to obtain, and can be rapidly performed by
Mutation transformation.The experiment proved that, this albuminoid has irisin domain similar characteristic, body white fat can be converted to palm fibre
Color fat, causes energy expenditure and immunostimulant, thus for prevention or treating the disease excessively causing because of Energy intaking/storage
Or state provides a kind of new effective way.It is mainly shown as minimizing body white accumulation of fat, adjustment blood glucose and pancreas
Island element level, mitigates body pressure, thus reaching effect for the treatment of obesity；Improve and move back because of senile and organic function of nervous system
Change the hypomnesiss causing, improve memory ability；Reduce energy i (in vivo) storage level, slow down telomere and shorten speed, thus slowing down
Senility of humanbody.The regulation to natural signals path for the albumen of the present invention, has safely and efficiently advantage.
Brief description
Fig. 1 has the albumen of the irisin functional structure scattergram in Islet cells for the present invention；
Fig. 2 has the albumen of the irisin functional structure scattergram in rat skin cell for the present invention；
Under conditions of the albumen that Fig. 3 has irisin functional structure for the present invention exists in rat body, lipogenetic gene
Mrna expression figure；
Under conditions of the albumen that Fig. 4 has irisin functional structure for the present invention exists in rat body, ucp-1 gene
Mrna expression figure.
Specific embodiment
For the purpose of the present invention, technical scheme and beneficial effect are better described, below in conjunction with accompanying drawing and being embodied as
The invention will be further described for example.
Embodiment 1
A kind of albumen with irisin functional structure of the present embodiment, its aminoacid sequence is as shown in seq id no:1.
The preparation method described in the present embodiment with the albumen of irisin functional structure is: by corresponding to the present embodiment albumen
Dna sequence according to Pichia sp. preference codon optimization after, be built into pgapz α a plasmid.Electroporation enters competent yeast
Cell, screening obtains inheritance stability bacterial strain.Bacterial strain is inoculated after Optimal Medium according to 5% (v/v) ratio, high density fermentation 72
Hour, centrifugation fermented liquid supernatant, this supernatant is obtained people irisin a by ni column purification.Albumen by this preliminary purification
Again through fplc purification, collect and there is the purifying protein that complete sequence detects peak, as albumen described in the present embodiment.
Embodiment 2 present invention has the detection in Islet cells and Skin Cell of the albumen of irisin functional structure
The albumen that embodiment 1 is had irisin functional structure is mixed with normal saline under suitable dilution ratio gradient,
Female 4 week old wistar rats are given in intramuscular injection, every injection in 48 hours once, co-injection 3 times.After last injection, 48 is little
When detection rat tissue cell in the present invention there is the protein content of irisin functional structure.The present invention has irisin function knot
Distribution in Islet cells for the albumen of structure is as shown in figure 1, the present invention has the albumen of irisin functional structure in rat
Distribution in Skin Cell is as shown in Figure 2.
Embodiment 3 present invention has albumen lipogenetic gene and brown fat conversion in rat body of irisin functional structure
Gene expression detection
The albumen that embodiment 1 is had irisin functional structure is mixed with normal saline under suitable dilution ratio gradient,
Female 4 week old wistar rats are given in intramuscular injection, every injection in 48 hours once, co-injection 3 times.After last injection, 48 is little
When detection rat tissue cell in promote white and yellow fat to switch to the gene mrna expression of brown fat.The present invention has
Under conditions of the albumen having irisin functional structure exists in rat body, lipogenetic gene mrna expression as shown in figure 3,
Ucp-1 gene mrna expression is as shown in Figure 4.
From Fig. 3 and Fig. 4, under conditions of people irisin a exists in vivo, lipogenetic gene fabp4, adipq are in conversion
Significant change does not occur in brown adipose tissue afterwards, in cfd brown adipose tissue in post-conversion, downward occurs, pparg exists
Then occur in brown adipose tissue after conversion substantially raising (Fig. 3)；And brown fat conversion key gene ucp-1 occur in that bright
Aobvious rise (Fig. 4).
Last should be noted that above example is only in order to illustrate technical scheme rather than to present invention guarantor
The restriction of shield scope, although being explained in detail to the present invention with reference to preferred embodiment, those of ordinary skill in the art should
Understand, technical scheme can be modified or equivalent, without deviating from the essence of technical solution of the present invention
And scope.
Claims (10)
1. a kind of albumen with irisin functional structure it is characterised in that: the aminoacid sequence of described albumen such as seq id
Shown in no:1.
2. a kind of albumen with irisin functional structure it is characterised in that: described albumen is following (a) or (b):
A () aminoacid sequence being had with albumen as described in claim 1 obtained by modifying shown in seq id no:1 is equal to
The protein derivatives of function；
B () aminoacid sequence as shown in seq id no:1 through the replacement of one or more amino acid residues, disappearance or adds institute
The protein derivatives with albumen described in claim 1 with identical functions obtaining.
3. a kind of coding has the polynucleotide of the albumen of irisin functional structure as claimed in claim 1.
4. a kind of compositionss containing the albumen as claimed in claim 1 with irisin functional structure.
5. compositionss as claimed in claim 4 it is characterised in that: described compositionss be pharmaceutical composition, cosmetic composition
Or Halth-care composition.
6. compositionss as claimed in claim 5 it is characterised in that: described compositionss be pharmaceutical composition, described drug regimen
Thing also comprises pharmaceutical carrier.
7. compositionss as claimed in claim 6 it is characterised in that: described pharmaceutical carrier comprises Lactose, dextrose, sucrose, mountain
At least one in pears alcohol, Mannitol, starch.
8. compositionss as claimed in claims 6 or 7 it is characterised in that: described pharmaceutical composition also comprises lubricant, moistening
Agent, sweetener, fumet, emulsifying agent, suspending agent and preservative.
9. compositionss as claimed in claim 5 it is characterised in that: described compositionss be cosmetic composition when, described cosmetic
Product compositionss also comprise adjuvant；When described compositionss are Halth-care composition, described Halth-care composition also comprises health product and uses
Carrier.
10. there is the albumen of irisin functional structure as claimed in claim 1 or combine as described in any one of claim 4～9
Thing is preparing obesity treating medicine, antiaging agent, the application improving in memory medicine or anti-aging cosmetics.
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| CN112999106A (en) * | 2019-12-18 | 2021-06-22 | 江苏天晟药业股份有限公司 | Natural moisturizing liquid and preparation method thereof |
| WO2023184332A1 (en) * | 2022-03-31 | 2023-10-05 | 深圳先进技术研究院 | Ovary-targeting polypeptide and use thereof |
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