U.S. patent application number 17/597198 was filed with the patent office on 2022-08-11 for composition for prevention or treatment of metabolic disorders or muscular diseases comprising extracellular vesicles derived from lactobacillus bacteria.
This patent application is currently assigned to MD HEALTHCARE INC.. The applicant listed for this patent is MD HEALTHCARE INC.. Invention is credited to Yoon-Keun KIM.
Application Number | 20220249581 17/597198 |
Document ID | / |
Family ID | |
Filed Date | 2022-08-11 |
United States Patent
Application |
20220249581 |
Kind Code |
A1 |
KIM; Yoon-Keun |
August 11, 2022 |
COMPOSITION FOR PREVENTION OR TREATMENT OF METABOLIC DISORDERS OR
MUSCULAR DISEASES COMPRISING EXTRACELLULAR VESICLES DERIVED FROM
LACTOBACILLUS BACTERIA
Abstract
Provided is a composition for preventing or treating a metabolic
disease or muscle disease, which includes vesicles derived from
bacteria of the genus Lactobacillus. Confirmed, when vesicles
derived from bacteria of the genus Lactobacillus were administered
into an animal model with a metabolic disease caused by a high fat,
the vesicles effectively inhibit metabolic diseases caused by a
high fat diet, and increase homeostasis to metabolic stress by
activating AMPK signaling in myocytes, and therefore, the vesicles
derived from bacteria of the genus Lactobacillus according to the
presently claimed subject matter can be effectively used in
development of pharmaceuticals or health functional foods for
preventing, improving symptoms or treating metabolic diseases such
as obesity and muscle diseases.
Inventors: |
KIM; Yoon-Keun; (Paju-Si,
Gyeonggi-do, KR) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
MD HEALTHCARE INC. |
Seoul |
|
KR |
|
|
Assignee: |
MD HEALTHCARE INC.
Seoul
KR
|
Appl. No.: |
17/597198 |
Filed: |
June 14, 2021 |
PCT Filed: |
June 14, 2021 |
PCT NO: |
PCT/KR2021/007369 |
371 Date: |
December 29, 2021 |
International
Class: |
A61K 35/747 20060101
A61K035/747; A61P 3/04 20060101 A61P003/04; A61P 21/00 20060101
A61P021/00; A61K 9/127 20060101 A61K009/127; A61P 3/10 20060101
A61P003/10; A23L 33/00 20060101 A23L033/00; A23L 33/135 20060101
A23L033/135 |
Foreign Application Data
Date |
Code |
Application Number |
Jun 16, 2020 |
KR |
10-2020-0072685 |
Jun 8, 2021 |
KR |
10-2021-0073948 |
Claims
1. A method for alleviating or treating a metabolic disease or a
muscle disease, the method comprising administering to a subject in
need thereof a composition comprising an effective amount of
vesicles derived from bacteria of the genus Lactobacillus.
2. The method of claim 1, wherein the bacteria of the genus
Lactobacillus is Lactobacillus paracasei or Lactobacillus
rhamnosus.
3. The method of claim 1, wherein the metabolic disease is selected
from the group consisting of obesity, metabolic syndrome,
hyperinsulinemia, hyperlipidemia, hypertriglyceridemia,
hypercholesterolemia, dyslipidemia, diabetes, diabetic nephropathy,
diabetic retinopathy, fatty liver, non-alcoholic steatohepatitis
and arteriosclerosis.
4. The method of claim 1, wherein the muscle disease is one or more
selected from the group consisting of atony, muscular atrophy,
muscular dystrophy, myasthenia, cachexia and sarcopenia.
5. The method of claim 1, wherein the vesicles have an average
diameter of 10 to 1000 nm.
6. The method of claim 1, wherein the vesicles are isolated from
culture solution of bacteria of the genus Lactobacillus.
7. The method of claim 1, wherein the vesicles are isolated from a
food prepared by adding bacteria of the genus Lactobacillus.
8. The method of claim 1, wherein the vesicles are naturally or
artificially secreted from bacteria of the genus Lactobacillus.
9. The method of claim 1, wherein the composition is a
pharmaceutical composition or a food composition.
10. A method for improving a muscle function, the method comprising
administering to a subject in need thereof a composition comprising
an effective amount of vesicles derived from bacteria of the genus
Lactobacillus.
11. A method for enhancing exercise performance capacity, the
method comprising administering to a subject in need thereof a
composition comprising an effective amount of vesicles derived from
bacteria of the genus Lactobacillus as.
12.-17. (canceled)
Description
TECHNICAL FIELD
[0001] The present invention relates to a composition for
preventing, improving, or treating a metabolic disease or muscle
disease, comprising vesicles derived from bacteria of the genus
Lactobacillus as an active ingredient, and the like.
[0002] This application claims priority to and the benefit of
Korean Patent Application Nos. 10-2020-0072685 and 10-2021-0073948
filed in the Korean Intellectual Property Office on Jun. 16, 2020
and Jun. 8, 2021, respectively, and all the contents disclosed in
the specification and drawings of the applications are incorporated
in this application.
BACKGROUND ART
[0003] Metabolic diseases are disease occurring due to metabolic
disorders in the body. Generally, metabolic diseases are caused by
an imbalance of carbohydrates, lipids, proteins, vitamins,
electrolytes and water, and include, for example, obesity,
diabetes, hyperlipidemia, arteriosclerosis, fatty liver and high
blood pressure. Among them, type 2 diabetes relating to obesity is
a type of diabetes mainly occurring in adulthood and is
characterized by resistance to insulin. When the insulin receptor
itself is reduced or its sensitivity is decreased, or there is a
problem with the secondary messenger causing glycogen synthesis in
cells, sensitivity to insulin may decrease. Accordingly, type 2
diabetes is called non-insulin-dependent diabetes and accounts for
85 to 90% of diabetes.
[0004] Bacteria of the genus Lactobacillus is known as
representative good bacteria secreting lactic acid. Among the
Lactobacillus species, Lactobacillus paracasei is a gram-positive
species of the class Bacilli, which grows well in an anaerobic
environment as well as an aerobic environment and is known as a
symbiotic bacterium in the vagina of women. Bacteria secrete
extracellular vesicles (EVs) often called nanovesicles, as
proteolipids with a double membrane structure, into an
extracellular environment for intracellular exchange of proteins,
lipids or genes. Vesicles derived from gram-positive bacteria such
as Lactobacillus paracasei include peptidoglycan and lipoteichoic
acid, which are constituents of bacterial cell walls, in addition
to bacteria-derived proteins and nucleic acids.
[0005] However, vesicles secreted from bacteria of the genus
Lactobacillus or Lactobacillus paracasei have not been used to
prevent or treat metabolic diseases such as obesity, metabolic
syndrome, hyperinsulinemia, hyperlipidemia, hypertriglyceridemia,
hypercholesterolemia, dyslipidemia, diabetes, diabetic nephropathy,
fatty liver, nonalcoholic steatohepatitis and arteriosclerosis.
DISCLOSURE
Technical Problem
[0006] As a result of earnestly conducting a study to evaluate
whether vesicles derived from bacteria of the genus Lactobacillus
such as Lactobacillus paracasei and Lactobacillus rhamnosus have a
therapeutic effect on metabolic diseases, the inventors observed
that administration of bacteria of the genus Lactobacillus-derived
vesicles into animal models with obesity and diabetes caused by a
high-fat diet effectively inhibits obesity and diabetes, and based
on this, the present invention was completed.
[0007] Thus, the present invention is directed to providing a
composition for preventing, alleviating, or treating a metabolic
disease, comprising vesicles derived from bacteria of the genus
Lactobacillus as an active ingredient.
[0008] In addition, the present invention is directed to providing
a composition for preventing, alleviating, or treating a muscle
disease, comprising vesicles derived from bacteria of the genus
Lactobacillus as an active ingredient.
[0009] In addition, the present invention is directed to providing
a food composition for improving a muscle function, comprising
vesicles derived from bacteria of the genus Lactobacillus as an
active ingredient.
[0010] In addition, the present invention is directed to providing
a food composition for enhancing exercise performance capacity,
comprising vesicles derived from bacteria of the genus
Lactobacillus as an active ingredient.
[0011] However, a technical problem to be achieved by the present
invention is not limited to the aforementioned problems, and the
other problems that are not mentioned may be clearly understood by
a person skilled in the art from the following description.
Technical Solution
[0012] To achieve the object of the present invention as described
above, the present invention provides a pharmaceutical composition
for preventing or treating a metabolic disease, comprising vesicles
derived from bacteria of the genus Lactobacillus as an active
ingredient.
[0013] In addition, the present invention provides a food
composition for preventing or alleviating a metabolic disease,
comprising vesicles derived from bacteria of the genus
Lactobacillus as an active ingredient.
[0014] As an exemplary embodiment of the present invention, the
bacteria of the genus Lactobacillus may be Lactobacillus paracasei
or Lactobacillus rhamnosus, but is not limited thereto.
[0015] As another exemplary embodiment of the present invention,
the food composition may be a health functional food composition,
but is not limited thereto.
[0016] As another exemplary embodiment of the present invention,
the metabolic disease may be one or more diseases selected from the
group consisting of obesity, metabolic syndrome, hyperinsulinemia,
hyperlipidemia, hypertriglyceridemia, hypercholesterolemia,
dyslipidemia, diabetes, diabetic nephropathy, diabetic retinopathy,
fatty liver, non-alcoholic steatohepatitis and
arteriosclerosis.
[0017] As another exemplary embodiment of the present invention,
the vesicles may have an average diameter of 10 to 1000 nm.
[0018] As another exemplary embodiment of the present invention,
the vesicles may be isolated from culture solution of bacteria of
the genus Lactobacillus.
[0019] As another exemplary embodiment of the present invention,
the vesicles may be obtained using vesicles isolated from a food
prepared by adding bacteria of the genus Lactobacillus.
[0020] As another exemplary embodiment of the present invention,
the vesicles may be naturally or artificially secreted from
bacteria of the genus Lactobacillus.
[0021] In addition, the present invention provides a method for
preventing or treating a metabolic disease, the method comprising
administering the composition to an individual.
[0022] In addition, the present invention provides a use of a
composition comprising vesicles derived from bacteria of the genus
Lactobacillus as an active ingredient for preventing or treating
metabolic diseases.
[0023] In addition, the present invention provides a use of
vesicles derived from bacteria of the genus Lactobacillus for
preparing a drug for preventing or treating a metabolic
disease.
[0024] In addition, the present invention provides a pharmaceutical
composition for preventing or treating a muscle disease, comprising
vesicles derived from bacteria of the genus Lactobacillus as an
active ingredient.
[0025] In addition, the present invention provides a food
composition for improving a muscle function, comprising vesicles
derived from bacteria of the genus Lactobacillus as an active
ingredient.
[0026] In addition, the present invention provides a food
composition for enhancing exercise performance capacity, comprising
vesicles derived from bacteria of the genus Lactobacillus as an
active ingredient.
[0027] As an exemplary embodiment of the present invention, the
bacteria of the genus Lactobacillus may be Lactobacillus paracasei
or Lactobacillus rhamnosus.
[0028] As another exemplary embodiment of the present invention,
the muscle disease may be one or more selected from the group
consisting of atony, muscular atrophy, muscular dystrophy,
myasthenia, cachexia and sarcopenia.
[0029] In addition, the present invention provides a method for
preventing or treating a muscle disease, the method comprising
administering the composition to an individual.
[0030] In addition, the present invention provides a use of a
composition comprising vesicles derived from bacteria of the genus
Lactobacillus as an active ingredient for preventing or treating a
muscle disease.
[0031] In addition, the present invention provides a use of
vesicles derived from bacteria of the genus Lactobacillus for
preparing a drug for preventing or treating a muscle disease.
[0032] In addition, the present invention provides a method for
improving a muscle function or enhancing exercise performance
capacity, the method comprising administering a composition
comprising vesicles derived from bacteria of the genus
Lactobacillus as an active ingredient to an individual.
[0033] In addition, the present invention provides a use of a
composition comprising vesicles derived from bacteria of the genus
Lactobacillus as an active ingredient for improving a muscle
function or enhancing exercise performance capacity.
[0034] In addition, the present invention provides a use of
vesicles derived from bacteria of the genus Lactobacillus for
preparing a drug for improving a muscle function or enhancing
exercise performance capacity.
Advantageous Effects
[0035] The inventors confirmed that, when vesicles derived from
bacteria of the genus Lactobacillus were administered into an
animal model with a metabolic disease caused by a high fat western
diet, the vesicles not only reduce a body weight and a meal amount,
but also effectively inhibit metabolic disorders caused by a
western diet, and increase homeostasis to metabolic stress by
activating AMPK signaling in myocytes, and the vesicles derived
from bacteria of the genus Lactobacillus according to the present
invention can be effectively used in development of pharmaceuticals
or health functional foods for preventing, improving symptoms or
treating metabolic diseases and muscle diseases such as obesity,
metabolic syndrome, hyperinsulinemia, hyperlipidemia,
hypertriglyceridemia, hypercholesterolemia, dyslipidemia, diabetes,
diabetic nephropathy, diabetic retinopathy, fatty liver,
non-alcoholic steatohepatitis and arteriosclerosis.
DESCRIPTION OF DRAWINGS
[0036] FIG. 1 is a diagram for analyzing a protein pattern
contained in vesicles isolated from a Lactobacillus paracasei
culture through SDS-PAGE and a silver staining method.
[0037] FIG. 2 is a diagram of evaluating the distribution pattern
of vesicles after Lactobacillus paracasei vesicles are labeled with
fluorescence and orally administered.
[0038] FIG. 3 is an experimental protocol for confirming an effect
of treating a metabolic disease after Lactobacillus
paracasei-derived vesicles are orally administered into a mouse
model with a metabolic disease induced by a high fat diet.
[0039] FIG. 4 is a result of observing a body weight change after
Lactobacillus paracasei-derived vesicles are directly administered
orally into a mouse model with a metabolic disease induced by a
high fat diet.
[0040] FIG. 5 is an experimental protocol for evaluating
concentration dependency for an effect of treating a metabolic
disease after various concentrations of Lactobacillus
paracasei-derived vesicles (MDH-001) are orally administered into a
mouse model with a metabolic disease induced by a high fat
diet.
[0041] FIG. 6 is a result of evaluating a body weight change and
food intake after various concentrations of Lactobacillus
paracasei-derived vesicles are directly administered orally into a
mouse model with a metabolic disease induced by a high fat
diet.
[0042] FIG. 7 is a result of evaluating the degree of expression of
a GLUT4 transporter, which is a glucose receptor, after metformin,
E. coli-derived vesicles (EcEVs) or Lactobacillus paracasei-derived
vesicles (L-EVs) are administered into myocytes.
[0043] FIG. 8 is a result of evaluating the degree of glucose
uptake in myocytes after insulin, metformin, E. coli-derived
vesicles (EcEVs) or Lactobacillus paracasei-derived vesicles
(L-EVs) are administered into myocytes.
[0044] FIG. 9 is a result of evaluating AMPK activation for 1 hour
after myocytes are treated with insulin, metformin, various
concentrations of Lactobacillus paracasei-derived vesicles (L.
paracasei EVs).
[0045] FIG. 10 is a result of evaluating AMPK activation for 1 hour
after myocytes are treated with insulin, metformin, various
concentrations of Lactobacillus rhamnosus-derived vesicles (L.
rhamnosus EVs).
MODES OF THE INVENTION
[0046] The inventors confirmed that, in a mouse model with a
metabolic disease induced by a high fat diet, when vesicles derived
from bacteria of the genus Lactobacillus were administered orally,
food intake decreased, and a body weight increase was inhibited in
a dose-dependent manner.
[0047] In still another embodiment of the present invention, in a
mouse model with a metabolic disease induced by a high fat diet, it
was confirmed that when vesicles derived from bacteria of the genus
Lactobacillus were administered orally, a fasting blood sugar level
is suppressed.
[0048] In yet another embodiment of the present invention, when
vesicles derived from bacteria of the genus Lactobacillus were
administered into myocytes, it was confirmed that the expression of
GLUT4, which is an indicator of insulin resistance, and glucose
uptake in myocytes are increased by vesicles.
[0049] In yet another embodiment of the present invention, it was
confirmed that, when vesicles derived from bacteria of the genus
Lactobacillus were administered into myocytes, a mechanism of
increasing insulin resistance by vesicles is associated with AMPK
activation.
[0050] Thus, the present invention provides a pharmaceutical
composition for preventing, alleviating, or treating a metabolic
disease or a muscle disease, comprising vesicles derived from
bacteria of the genus Lactobacillus as an active ingredient.
[0051] In the present invention, the bacteria of the genus
Lactobacillus may be Lactobacillus paracasei or Lactobacillus
rhamnosus, but is not limited thereto.
[0052] As used herein, the term "vesicle" refers to a structure
formed of a nano-sized membrane secreted from various bacteria, and
in the present invention, the term collectively refers to all
structures formed of a membrane naturally secreted from bacteria of
the genus Lactobacillus, or artificially produced. The vesicles may
be isolated from a culture solution including bacterial cells of
bacteria of the genus Lactobacillus by using one or more methods
selected from the group consisting of centrifugation, ultra-high
speed centrifugation, high pressure treatment, extrusion,
sonication, cell lysis, homogenization, freezing-thawing,
electroporation, mechanical decomposition, chemical treatment,
filtration by filter, gel filtration chromatography, free-flow
electrophoresis, and capillary electrophoresis. Further, a process
such as washing for removing impurities and concentration of
obtained vesicles may be further included.
[0053] The vesicles of the present invention may be isolated from a
culture solution of bacteria of the genus Lactobacillus or a food
prepared by adding bacteria of the genus Lactobacillus, and the
vesicles may be naturally or artificially secreted from bacteria of
the genus Lactobacillus, but are not limited thereto.
[0054] The method for isolating vesicles from the culture solution
or fermented food of the bacteria of the genus Lactobacillus of the
present invention is not particularly limited as long as the
vesicles are included. For example, vesicles may be isolated using
a method such as centrifugation, ultra-high speed centrifugation,
filtration by a filter, gel filtration chromatography, free-flow
electrophoresis, or capillary electrophoresis, and a combination
thereof, and further, a process such as washing to remove
impurities and concentration of obtained vesicles may be further
included.
[0055] In the present invention, vesicles isolated by the method
may have an average diameter 10 to 1000 nm, 10 to 900 nm, 10 to 800
nm, 10 to 700 nm, 10 to 600 nm, 10 to 500 nm, 10 to 400 nm, 10 to
300 nm, 10 to 200 nm, 20 to 1000 nm, 20 to 900 nm, 20 to 800 nm, 20
to 700 nm, 20 to 600 nm, 20 to 500 nm, 20 to 400 nm, 20 to 300 nm,
20 to 200 nm, 30 to 1000 nm, 30 to 900 nm, 30 to 800 nm, 30 to 700
nm, 30 to 600 nm, 30 to 500 nm, 30 to 400 nm, 30 to 300 nm, 30 to
200 nm, 40 to 1000 nm, 40 to 900 nm, 40 to 800 nm, 40 to 700 nm, 40
to 600 nm, 40 to 500 nm, 40 to 400 nm, 40 to 300 nm, 40 to 200 nm,
20 to 180 nm, 30 to 180 nm, 40 to 180 nm, 20 to 170 nm, 20 to 160
nm, 40 to 160 nm, 45 to 155 nm, or 50 to 150 nm, but the average
diameter is not limited thereto.
[0056] The term "metabolic disease" used herein encompasses
diseases occurring due to metabolic disorders in the body.
Generally, metabolic diseases are caused by an imbalance of
carbohydrates, lipids, proteins, vitamins, electrolytes and water,
and include, for example, obesity, metabolic syndrome,
hyperinsulinemia, hyperlipidemia, hypertriglyceridemia,
hypercholesterolemia, dyslipidemia, diabetes, diabetic nephropathy,
diabetic retinopathy, fatty liver, non-alcoholic steatohepatitis
and arteriosclerosis.
[0057] The term "muscle disease" used herein may refer to a disease
caused by muscle wasting or degeneration, but the present invention
is not limited thereto. In the present invention, the muscle
disease may be one or more selected from the group consisting of
atony, muscular atrophy, muscular dystrophy, myasthenia, cachexia
and sarcopenia, but the present invention is not limited thereto.
Muscle wasting and degeneration are caused by genetic factors,
acquired factors, aging, etc. The composition of the present
invention has an effect of promoting a muscle increase, and the
muscle is not limited in type. A muscle increase is an improvement
in performance of a muscle, particularly, among body components,
and muscle mass may be increased by physical exercise and improved
endurance by a method of administering a material having a muscle
increasing effect into the body.
[0058] The amount of the vesicles in the composition of the present
invention may be appropriately adjusted depending on the symptoms
of a disease, the degree of progression of symptoms, the condition
of a patient, and the like, and may range from, for example, 0.0001
wt % to 99.9 wt % or 0.001 wt % to 50 wt % with respect to a total
weight of the composition, but the present invention is not limited
thereto. The amount ratio is a value based on the amount of dried
product from which a solvent is removed.
[0059] The pharmaceutical composition according to the present
invention may further include a suitable carrier, excipient, and
diluent which are commonly used in the preparation of
pharmaceutical compositions. The excipient may be, for example, one
or more selected from the group consisting of a diluent, a binder,
a disintegrant, a lubricant, an adsorbent, a humectant, a
film-coating material, and a controlled release additive.
[0060] The pharmaceutical composition according to the present
invention may be used by being formulated, according to commonly
used methods, into a form such as powders, granules,
sustained-release-type granules, enteric granules, liquids, eye
drops, elixirs, emulsions, suspensions, spirits, troches, aromatic
water, lemonades, tablets, sustained-release-type tablets, enteric
tablets, sublingual tablets, hard capsules, soft capsules,
sustained-release-type capsules, enteric capsules, pills,
tinctures, soft extracts, dry extracts, fluid extracts, injections,
capsules, perfusates, or a preparation for external use, such as
plasters, lotions, pastes, sprays, inhalants, patches, sterile
injectable solutions, or aerosols. The preparation for external use
may have a formulation such as creams, gels, patches, sprays,
ointments, plasters, lotions, liniments, pastes, or
cataplasmas.
[0061] As the carrier, the excipient, and the diluent that may be
included in the pharmaceutical composition according to the present
invention, lactose, dextrose, sucrose, oligosaccharides, sorbitol,
mannitol, xylitol, erythritol, maltitol, starch, acacia rubber,
alginate, gelatin, calcium phosphate, calcium silicate, cellulose,
methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone,
water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc,
magnesium stearate, and mineral oil may be used.
[0062] For formulation, commonly used diluents or excipients such
as fillers, thickeners, binders, wetting agents, disintegrants, and
surfactants are used.
[0063] As additives of tablets, powders, granules, capsules, pills,
and troches according to the present invention, excipients such as
corn starch, potato starch, wheat starch, lactose, white sugar,
glucose, fructose, D-mannitol, precipitated calcium carbonate,
synthetic aluminum silicate, dibasic calcium phosphate, calcium
sulfate, sodium chloride, sodium hydrogen carbonate, purified
lanolin, microcrystalline cellulose, dextrin, sodium alginate,
methyl cellulose, sodium carboxymethylcellulose, kaolin, urea,
colloidal silica gel, hydroxypropyl starch, hydroxypropyl
methylcellulose (HPMC) 1928, HPMC 2208, HPMC 2906, HPMC 2910,
propylene glycol, casein, calcium lactate, and Primojel.RTM.; and
binders such as gelatin, Arabic gum, ethanol, agar powder,
cellulose acetate phthalate, carboxymethylcellulose, calcium
carboxymethylcellulose, glucose, purified water, sodium caseinate,
glycerin, stearic acid, sodium carboxymethylcellulose, sodium
methylcellulose, methylcellulose, microcrystalline cellulose,
dextrin, hydroxycellulose, hydroxypropyl starch,
hydroxymethylcellulose, purified shellac, starch, hydroxypropyl
cellulose, hydroxypropyl methylcellulose, polyvinyl alcohol, and
polyvinylpyrrolidone may be used, and disintegrants such as
hydroxypropyl methylcellulose, corn starch, agar powder,
methylcellulose, bentonite, hydroxypropyl starch, sodium
carboxymethylcellulose, sodium alginate, calcium
carboxymethylcellulose, calcium citrate, sodium lauryl sulfate,
silicic anhydride, 1-hydroxypropylcellulose, dextran, ion-exchange
resin, polyvinyl acetate, formaldehyde-treated casein and gelatin,
alginic acid, amylose, guar gum, sodium bicarbonate,
polyvinylpyrrolidone, calcium phosphate, gelled starch, Arabic gum,
amylopectin, pectin, sodium polyphosphate, ethyl cellulose, white
sugar, magnesium aluminum silicate, a di-sorbitol solution, and
light anhydrous silicic acid; and lubricants such as calcium
stearate, magnesium stearate, stearic acid, hydrogenated vegetable
oil, talc, lycopodium powder, kaolin, Vaseline, sodium stearate,
cacao butter, sodium salicylate, magnesium salicylate, polyethylene
glycol (PEG) 4000, PEG 6000, liquid paraffin, hydrogenated soybean
oil (Lubri wax), aluminum stearate, zinc stearate, sodium lauryl
sulfate, magnesium oxide, Macrogol, synthetic aluminum silicate,
silicic anhydride, higher fatty acids, higher alcohols, silicone
oil, paraffin oil, polyethylene glycol fatty acid ether, starch,
sodium chloride, sodium acetate, sodium oleate, dl-leucine, and
light anhydrous silicic acid may be used.
[0064] As additives of liquids according to the present invention,
water, dilute hydrochloric acid, dilute sulfuric acid, sodium
citrate, monostearic acid sucrose, polyoxyethylene sorbitol fatty
acid esters (twin esters), polyoxyethylene monoalkyl ethers,
lanolin ethers, lanolin esters, acetic acid, hydrochloric acid,
ammonia water, ammonium carbonate, potassium hydroxide, sodium
hydroxide, prolamine, polyvinylpyrrolidone, ethylcellulose, and
sodium carboxymethylcellulose may be used.
[0065] In syrups according to the present invention, a white sugar
solution, other sugars or sweeteners, and the like may be used, and
as necessary, a fragrance, a colorant, a preservative, a
stabilizer, a suspending agent, an emulsifier, a viscous agent, or
the like may be used.
[0066] In emulsions according to the present invention, purified
water may be used, and as necessary, an emulsifier, a preservative,
a stabilizer, a fragrance, or the like may be used.
[0067] In suspensions according to the present invention,
suspending agents such as acacia, tragacanth, methylcellulose,
carboxymethylcellulose, sodium carboxymethylcellulose,
microcrystalline cellulose, sodium alginate, hydroxypropyl
methylcellulose (HPMC) 1828, HPMC 2906, HPMC 2910, and the like may
be used, and as necessary, a surfactant, a preservative, a
stabilizer, a colorant, and a fragrance may be used.
[0068] Injections according to the present invention may include:
solvents such as distilled water for injection, a 0.9% sodium
chloride solution, Ringer's solution, a dextrose solution, a
dextrose+sodium chloride solution, PEG, lactated Ringer's solution,
ethanol, propylene glycol, non-volatile oil-sesame oil, cottonseed
oil, peanut oil, soybean oil, corn oil, ethyl oleate, isopropyl
myristate, and benzene benzoate; cosolvents such as sodium
benzoate, sodium salicylate, sodium acetate, urea, urethane,
monoethylacetamide, butazolidine, propylene glycol, the Tween
series, amide nicotinate, hexamine, and dimethylacetamide; buffers
such as weak acids and salts thereof (acetic acid and sodium
acetate), weak bases and salts thereof (ammonia and ammonium
acetate), organic compounds, proteins, albumin, peptone, and gums;
isotonic agents such as sodium chloride; stabilizers such as sodium
bisulfite (NaHSO.sub.3) carbon dioxide gas, sodium metabisulfite
(Na.sub.2S.sub.2O.sub.5), sodium sulfite (Na.sub.2SO.sub.3),
nitrogen gas (N.sub.2), and ethylenediamine tetraacetic acid;
sulfating agents such as 0.1% sodium bisulfide, sodium formaldehyde
sulfoxylate, thiourea, disodium ethylenediaminetetraacetate, and
acetone sodium bisulfite; a pain relief agent such as benzyl
alcohol, chlorobutanol, procaine hydrochloride, glucose, and
calcium gluconate; and suspending agents such as sodium CMC, sodium
alginate, Tween 80, and aluminum monostearate.
[0069] In suppositories according to the present invention, bases
such as cacao butter, lanolin, Witepsol, polyethylene glycol,
glycerogelatin, methylcellulose, carboxymethylcellulose, a mixture
of stearic acid and oleic acid, Subanal, cottonseed oil, peanut
oil, palm oil, cacao butter+cholesterol, lecithin, lanette wax,
glycerol monostearate, Tween or span, imhausen, monolan(propylene
glycol monostearate), glycerin, Adeps solidus, buytyrum Tego-G,
cebes Pharma 16, hexalide base 95, cotomar, Hydrokote SP, S-70-XXA,
S-70-XX75(S-70-XX95), Hydrokote 25, Hydrokote 711, idropostal,
massa estrarium (A, AS, B, C, D, E, I, T), masa-MF, masupol,
masupol-15, neosuppostal-N, paramount-B, supposiro OSI, OSIX, A, B,
C, D, H, L, suppository base IV types AB, B, A, BC, BBG, E, BGF, C,
D, 299, suppostal N, Es, Wecoby W, R, S, M, Fs, and tegester
triglyceride matter (TG-95, MA, 57) may be used.
[0070] Solid preparations for oral administration include tablets,
pills, powders, granules, capsules, and the like, and such solid
preparations are formulated by mixing the composition with at least
one excipient, e.g., starch, calcium carbonate, sucrose, lactose,
gelatin, and the like. In addition to simple excipients, lubricants
such as magnesium stearate and talc are also used.
[0071] Examples of liquid preparations for oral administration
include suspensions, liquids for internal use, emulsions, syrups,
and the like, and these liquid preparations may include, in
addition to simple commonly used diluents, such as water and liquid
paraffin, various types of excipients, for example, a wetting
agent, a sweetener, a fragrance, a preservative, and the like.
Preparations for parenteral administration include an aqueous
sterile solution, a non-aqueous solvent, a suspension, an emulsion,
a freeze-dried preparation, and a suppository. Non-limiting
examples of the non-aqueous solvent and the suspension include
propylene glycol, polyethylene glycol, a vegetable oil such as
olive oil, and an injectable ester such as ethyl oleate.
[0072] The pharmaceutical composition according to the present
invention is administered in a pharmaceutically effective amount.
In the present invention, "the pharmaceutically effective amount"
refers to an amount sufficient to treat diseases at a reasonable
benefit/risk ratio applicable to medical treatment, and an
effective dosage level may be determined according to factors
including types of diseases of patients, the severity of disease,
the activity of drugs, sensitivity to drugs, administration time,
administration route, excretion rate, treatment period, and
simultaneously used drugs, and factors well known in other medical
fields.
[0073] The composition according to the present invention may be
administered as an individual therapeutic agent or in combination
with other therapeutic agents, may be administered sequentially or
simultaneously with therapeutic agents in the related art, and may
be administered in a single dose or multiple doses. It is important
to administer the composition in a minimum amount that can obtain
the maximum effect without any side effects, in consideration of
all the aforementioned factors, and this may be easily determined
by those of ordinary skill in the art.
[0074] The pharmaceutical composition of the present invention may
be administered to an individual via various routes. All
administration methods can be predicted, and the pharmaceutical
composition may be administered via, for example, oral
administration, subcutaneous injection, intravenous injection,
intramuscular injection, intrathecal (space around the spinal cord)
injection, sublingual administration, administration via the buccal
mucosa, intrarectal insertion, intravaginal insertion, ocular
administration, intra-aural administration, intranasal
administration, inhalation, spraying via the mouth or nose,
transdermal administration, percutaneous administration, or the
like.
[0075] The pharmaceutical composition of the present invention is
determined depending on the type of a drug, which is an active
ingredient, along with various related factors such as a disease to
be treated, administration route, the age, gender, and body weight
of a patient, and the severity of diseases. Specifically, the
effective amount of the composition according to the present
invention may vary depending on the patient's age, sex, and body
weight, and generally, 0.001 to 150 mg of the composition and
preferably, 0.01 to 100 mg of the composition, per 1 kg of the body
weight, may be administered daily or every other day or may be
administered once to three times a day. However, since the
effective amount may be increased or decreased depending on the
administration route, the severity of obesity, gender, body weight,
age, and the like, the dosage is not intended to limit the scope of
the present invention in any way.
[0076] As used herein, the "subject" refers to a subject in need of
treatment of a disease, and more specifically, refers to a mammal
such as a human or a non-human primate, a mouse, a rat, a dog, a
cat, a horse, and a cow, but the present invention is not limited
thereto.
[0077] As used herein, the "administration" refers to providing a
subject with a predetermined composition of the present invention
by using an arbitrary appropriate method.
[0078] The term "prevention" as used herein means all actions that
inhibit or delay the onset of a target disease. The term
"treatment" as used herein means all actions that alleviate or
beneficially change a target disease and abnormal metabolic
symptoms caused thereby via administration of the pharmaceutical
composition according to the present invention. The term
"improvement" as used herein means all actions that reduce the
degree of parameters related to a target disease, e.g., symptoms
via administration of the composition according to the present
invention.
[0079] In addition, the present invention provides a food
composition for preventing or alleviating a metabolic disease or a
muscle disease, comprising vesicles derived from bacteria of the
genus Lactobacillus as an active ingredient.
[0080] In addition, the present invention provides a food
composition for improving a muscle function, comprising vesicles
derived from bacteria of the genus Lactobacillus as an active
ingredient.
[0081] In addition, the present invention provides a food
composition for enhancing exercise performance capacity, comprising
vesicles derived from bacteria of the genus Lactobacillus as an
active ingredient.
[0082] The improvement in muscle function refers to strengthening
of the intrinsic properties or functions of muscles such as
increasing muscle mass, improving muscular strength and recovering
muscle fatigue.
[0083] The "muscle" used herein encompasses a sinew, muscle and a
tendon, and the "muscle function" refers to an ability to exert a
force by muscle contraction and includes muscular strength which is
an ability to exert maximum contracting power to overcome
resistance, muscular endurance which is an ability to exhibit how
long or how many times muscle can repeat contraction and relaxation
at a given weight, and explosive muscle strength which is an
ability to exert a strong force within a short period of time. Such
muscle functions are controlled by the liver, and proportional to
muscle mass. The term "improving a muscle function" refers to
enhancing a muscle function for the better.
[0084] The term "enhancing exercise performance capacity" means an
effect of enhancing a muscle function such as muscular strength or
muscular endurance, and preferably, an increase in muscular
strength or muscular endurance. Accordingly, the composition has an
effect of increasing exercise endurance, strengthening muscular
strength, enhancing sense of balance, and/or enhancing exercise
adaptation. One of the representative methods for improving
exercise performance capacity by promoting energy consumption is a
method of generating ATP energy by increasing fatty acid oxidation
caused by mitochondria. AMPK, pAMPK, PPAR.delta., ERR.alpha., Tfam,
and the like are known as factors related to the improvement in
exercise performance capacity.
[0085] The food composition may be a health functional food
composition, but is not limited thereto.
[0086] The vesicles according to the present invention may be used
by adding an active ingredient as is to food or may be used
together with other foods or food ingredients, but may be
appropriately used according to a typical method. The mixed amount
of the active ingredient may be suitably determined depending on
the purpose of use thereof (for prevention or alleviation). In
general, when a food or beverage is prepared, the composition of
the present invention is added in an amount of 15 wt % or less,
preferably 10 wt % or less based on the raw materials. However, for
long-term intake for the purpose of health and hygiene or for the
purpose of health control, the amount may be less than the
above-mentioned range, and the vesicles have no problem in terms of
stability, so the active ingredient may be used in an amount more
than the above-mentioned range.
[0087] The type of food is not particularly limited. Examples of
food to which the material may be added include meats, sausage,
bread, chocolate, candies, snacks, confectioneries, pizza, instant
noodles, other noodles, gums, dairy products including ice creams,
various soups, beverages, tea, drinks, alcoholic beverages, vitamin
complexes, and the like, and include all health functional foods in
a typical sense.
[0088] The health beverage composition according to the present
invention may contain various flavors or natural carbohydrates, and
the like as additional ingredients as in a typical beverage. The
above-described natural carbohydrates may be monosaccharides such
as glucose and fructose, disaccharides such as maltose and sucrose,
polysaccharides such as dextrin and cyclodextrin, and sugar
alcohols such as xylitol, sorbitol, and erythritol. As a sweetener,
it is possible to use a natural sweetener such as thaumatin and
stevia extract, a synthetic sweetener such as saccharin and
aspartame, and the like. The proportion of the natural
carbohydrates is generally about 0.01 to 0.20 g, or about 0.04 to
0.10 g per 100 ml of the composition of the present invention.
[0089] In addition to the aforementioned ingredients, the
composition of the present invention may contain various nutrients,
vitamins, electrolytes, flavors, colorants, pectic acids and salts
thereof, alginic acid and salts thereof, organic acids, protective
colloid thickeners, pH adjusters, stabilizers, preservatives,
glycerin, alcohols, carbonating agents used in carbonated drinks,
and the like. In addition, the composition of the present invention
may contain flesh for preparing natural fruit juice, fruit juice
drinks, and vegetable drinks. These ingredients may be used either
alone or in combinations thereof. The proportion of these additives
is not significantly important, but is generally selected within a
range of 0.01 to 0.20 part by weight per 100 parts by weight of the
composition of the present invention.
[0090] Hereinafter, preferred Examples for helping the
understanding of the present invention will be suggested. However,
the following Examples are provided only to more easily understand
the present invention, and the contents of the present invention
are not limited by the following Examples.
EXAMPLES
Example 1: Isolation of Vesicles Derived from Lactobacillus
paracasei
[0091] To isolate vesicles derived from representative bacteria of
the genus Lactobacillus such as Lactobacillus paracasei and
Lactobacillus rhamnosus-derived vesicles (extracellular vesicles;
EVs), the Lactobacillus strains were inoculated into an MRS (de
Man-Rogosa and Sharpe) medium, incubated at 37.degree. C. and 200
rpm to have an absorbance (OD.sub.600 nm) of 1.0 to 1.5, and
reinoculated into a Luria Bertani (LB) medium and incubated. Then,
a supernatant from which bacterial cells had been removed was
obtained by recovering the culture solution including bacterial
cells and performing centrifugation at 4.degree. C. and 10,000 g
for 20 minutes. The obtained supernatant was again filtered using a
0.22 .mu.m filter, and the filtered supernatant was concentrated to
a volume of 50 mL or less using a 100 kDa Pellicon 2 Cassette
filter membrane (Merck Millipore) and a MasterFlex pump system
(Cole-Parmer). A vesicle derived from bacteria of Lactobacillus was
isolated by filtering the concentrated supernatant again using a
0.22 .mu.m filter. In the following examples, experiments were
performed using the isolated vesicle.
Example 2. Characterization of Vesicles Derived from Lactobacillus
paracasei
[0092] To confirm the characteristics of vesicles derived from
Lactobacillus paracasei (extracellular vesicles; EVs) acquired by
the method of Example 1, protein quantification, measurement of
particle size and distribution and protein pattern analysis were
performed.
[0093] As a result of protein quantification using a BCA method, it
was confirmed that an average protein concentration is 3 to 5
mg/mL. In addition, to confirm the size and distribution of
vesicles derived from Lactobacillus paracasei, nanoparticle
tracking analysis (NTA) was performed using an NS300 instrument
(Malvern Panalytical). After diluting the concentration of a sample
to 1 mg/mL based on a protein concentration, the sample was diluted
100 to 2,000 times to adjust a `particles/frame` value to 20 to
100.
[0094] As a result, it was confirmed that the extracellular
vesicles have a size of 50 to 150 nm, and contain 1.0E+11
particles/mL or more per 1 mL.
[0095] In addition, to confirm a protein pattern of vesicles
derived from Lactobacillus paracasei, sodium dodecyl
sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and silver
staining were performed.
[0096] As shown in FIG. 1, it was confirmed that the vesicles
derived from Lactobacillus paracasei are observed in five main
bands (near 130, 95, 85, 70 and 45 kDa).
Example 3. Pharmacokinetic Characteristics of Vesicles Derived from
Lactobacillus paracasei
[0097] To confirm the pharmacokinetic properties such as systemic
absorption and distribution patterns in oral administration of
vesicles derived from Lactobacillus paracasei, a distribution in
the body was confirmed by the following method.
[0098] Vesicles derived from Lactobacillus paracasei labeled with
the phosphor Cy7 were orally administered into mice, and to confirm
the infiltration pattern into various organs after 0, 1, 3, 6, 24,
32, 48, 56 and 72 hours, blood, the heart, lungs, liver, kidneys,
spleen, gastrointestinal tract and brain were obtained. A
fluorescent signal from the obtained tissue was observed using
optical imaging equipment (Davinch-Invivo Fluoro Chemi (western);
Davinch-K).
[0099] As shown in FIG. 2, it was confirmed that, after the
administration of vesicles derived from Lactobacillus paracasei,
the vesicles were absorbed into the stomach within 1 hour,
distributed into the stomach, small and large intestines and lungs
at 3 hours, and also distributed in the liver and brain after 3
hours. That is, from the result of continuously observing
fluorescent signals of extracellular vesicles in various tissues
from 32 to 48 hours, it was confirmed that in the case of oral
administration of extracellular vesicles, the vesicles are
distributed throughout the entire body including the stomach,
intestines, lungs, liver and brain until 48 hours.
Example 4. Obesity Treating Effect of Vesicles Derived from
Lactobacillus paracasei in Mice with Metabolic Diseases Induced by
High Fat Diet
[0100] To confirm whether the vesicles derived from Lactobacillus
paracasei obtained in Example 1 inhibit a metabolic disease induced
by a high fat diet, an experiment was performed by the following
method.
[0101] Specifically, according to the experimental protocol shown
in FIG. 3, a normal mouse fed a regular diet (RD) and a mouse fed a
high fat diet (HFD) for 4 months to induce a metabolic disease were
prepared. The vesicles derived from Lactobacillus paracasei
obtained in Example 1 were administered into the metabolic disease
model at 10 .mu.g per mouse every 2 days for 3 weeks. Here, a
negative control (NC) was fed a normal diet, and a positive control
(obese) was fed a high fat diet. As control drugs, vesicles derived
from Lactobacillus rhamnosus (L. rhamnosus), vesicles derived from
Lactobacillus lactis (L. lactis), and vesicles derived from Proteus
mirabilis (P. mirabilis) were orally administered at the same dose
as the vesicles derived from Lactobacillus paracasei. In addition,
while the vesicles were administered every 2 days, a body weight
was measured.
[0102] As shown in FIG. 4, compared to a high fat diet-fed positive
control (obese) to which a drug was not administered, in a group to
which vesicles derived fromLactobacillus paracasei (L. paracasei)
were administered and a group to which vesicles derived from
Lactobacillus rhamnosus (L. rhamnosus) were administered, body
weights were reduced, and in the group ingesting vesicles derived
from Lactobacillus paracasei, a body weight loss was more clearly
observed.
[0103] However, the group to which vesicles derived from Proteus
mirabilis (P. mirabilis) were administered showed similar body
weights to those of the high fat diet-fed positive control, and
compared to the group fed only a high fat diet, the Proteus
mirabilis group even showed increased body weights, and the L.
lactis-derived vesicle-administered group showed a slight body
weight loss.
Example 5. Dose Dependence on Therapeutic Effect of Vesicles
Derived from Lactobacillus paracasei in Mouse with Metabolic
Disease Induced by High Fat Diet
[0104] To evaluate efficacy of treating a metabolic disease induced
by a high fat diet according to a dose of vesicles derived from
Lactobacillus paracasei, an experiment was performed by the
following method.
[0105] As shown in FIG. 5, a mouse model in which obesity and
diabetes was induced by a high fat diet (60% High fat diet; HFD)
for 2 weeks were prepared, the vesicles derived from Lactobacillus
paracasei (MDH-001) obtained in Example 1 were administered at a
dose of 3, 10 or 30 mg/kg per weight (g) of a mouse for 8 weeks.
Here, as a positive control, a mouse group prepared by
administering PBS into the moused model in which obesity and
diabetes was induced by a high fat diet (60% High fat diet; HFD)
for 2 weeks was used. While administering the vesicles every 2
days, body weights were measured.
[0106] As shown in FIG. 6, it was confirmed that the greater the
dose of the vesicles administered for 8 weeks, the clearer the
effect of losing body weight, and in the mouse group administered
30 mg/kg of vesicles, compared to the PBS-administered mouse group,
it was confirmed that a body weight was reduced by about 5 to 7%.
The effect of reducing food intake in a dose-dependent manner of
the administered vesicles was also confirmed.
[0107] From the above result, it was confirmed that the vesicles
derived from Lactobacillus paracasei inhibit obesity in a
dose-dependent manner, and are associated with a decrease in food
intake.
Example 6. Effect of Vesicles Derived from Lactobacillus paracasei
on Glucose Metabolism in Myocytes
[0108] To evaluate the effect of vesicles derived from
Lactobacillus paracasei on expression of glucose transporter type 4
(GLUT4) in myocytes, myocytes were treated in vitro with 10
.mu.g/ml of vesicles derived from Lactobacillus paracasei (L-EVs)
for 1 hour. Afterward, a degree of expression of GLUT4 on the cell
membrane was assessed by o-phenylenediamine (OPD) assay. As
controls, vesicles derived from E. coli (EcEVs) and metformin were
used.
[0109] As a result, as shown in FIG. 7, it was confirmed that the
GLUT4 expression was not increased by vesicles derived from E. coli
(EcEVs), but increased by vesicles derived from Lactobacillus
paracasei and metformin.
[0110] In addition, to evaluate an effect of vesicles derived from
Lactobacillus paracasei on glucose metabolism in myocytes, myocytes
were treated in vitro with 10 .mu.g/ml of vesicles derived from
Lactobacillus paracasei for 1 hour. Afterward, glucose uptake was
confirmed with radioactive isotopes.
[0111] As a result, as shown in FIG. 8, glucose uptake was not
increased by vesicles derived from E. coli (EcEVs), but increased
by vesicles derived from Lactobacillus paracasei (L-EVs) and
metformin.
[0112] From the above result, it can be seen that the vesicles
derived from Lactobacillus paracasei inhibit insulin resistance in
an organ on which insulin acts such as myocytes, thereby increasing
insulin reactivity.
Example 7. Effect of Vesicles Derived from Lactobacillus paracasei
on AMPK Activation in Myocytes
[0113] During fasting or exercise, energy in myocytes is depleted,
so ATP production decreases and AMP production increases. Here, it
is well known that activation of AMPK signaling increases
homeostasis to metabolic stress in cells. To evaluate whether the
obesity and insulin resistance inhibitory effect by the vesicles
derived from Lactobacillus paracasei is associated with AMPK
signaling, an experiment was performed by the following method.
That is, myocytes were treated in vitro with vesicles derived from
Lactobacillus paracasei (L-EVs) at a concentration of 0, 0.1, 1 or
10 .mu.g/ml for 1 hour. Afterward, a level of AMPK phosphorylation
(pAMPK), which is an AMPK signaling indicator, was measured by
western blotting. As control drugs, insulin and metformin were
used.
[0114] As a result, as shown in FIG. 9, pAMPK expression was
inhibited by the control drug, insulin, and increased by metformin.
In addition, when vesicles derived from Lactobacillus paracasei
were treated, pAMPK expression was increased in a vesicle
concentration-dependent manner. This means that the obesity and
insulin resistance inhibitory effect of the vesicles derived from
Lactobacillus paracasei is closely related to AMPK signaling that
maintains cell homeostasis by metabolic stress.
Example 8. Effect of Vesicles Derived from Lactobacillus rhamnosus
on AMPK Activation in Myocytes
[0115] To evaluate whether an obesity and insulin resistance
inhibitory effect by vesicles derived from Lactobacillus rhamnosus
is associated with AMPK signaling, an experiment was performed by
the following method. That is, myocytes were treated in vitro with
vesicles derived from Lactobacillus rhamnosus (L-EVs) at 0, 0.1, 1,
10 .mu.g/ml for 1 hour. Afterward, a level of AMPK phosphorylation
(pAMPK), which is an AMPK signaling indicator, was measured by
western blotting. As control drugs, insulin and metformin were
used.
[0116] As a result, as shown in FIG. 10, pAMPK expression was
inhibited by the control drug, insulin, and increased by metformin.
In addition, when vesicles derived from Lactobacillus rhamnosus
were treated, pAMPK expression was increased in a vesicle
concentration-dependent manner. This means that the obesity and
insulin resistance inhibitory effect of the vesicles derived from
Lactobacillus rhamnosus is closely related to AMPK signaling that
maintains cell homeostasis by metabolic stress.
[0117] The above-described description of the present invention is
provided for illustrative purposes, and those of ordinary skill in
the art to which the present invention pertains will understand
that the present invention can be easily modified into other
specific forms without changing the technical spirit or essential
features of the present invention. Therefore, it should be
understood that the above-described Examples are illustrative only
in all aspects and are not restrictive.
INDUSTRIAL APPLICABILITY
[0118] The inventors confirmed that, when vesicles derived from
bacteria of the genus Lactobacillus were administered to a high fat
western diet-induced metabolic disease animal model, not only can a
body weight and a meal amount be reduced, but also a metabolic
disorder by a western diet can be effectively inhibited, and
homeostasis to metabolic stress was increased by activating AMPK
signaling in myocytes. Therefore, the vesicles derived from
bacteria of the genus Lactobacillus according to the present
invention can be effectively used in development of pharmaceuticals
or health functional foods for preventing, improving symptoms or
treating metabolic diseases and muscle diseases, and thus have
industrial applicability.
* * * * *