KR101736033B1 - Lactobacillus sakei with activity of anti-obesity - Google Patents
Lactobacillus sakei with activity of anti-obesity Download PDFInfo
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- KR101736033B1 KR101736033B1 KR1020160056578A KR20160056578A KR101736033B1 KR 101736033 B1 KR101736033 B1 KR 101736033B1 KR 1020160056578 A KR1020160056578 A KR 1020160056578A KR 20160056578 A KR20160056578 A KR 20160056578A KR 101736033 B1 KR101736033 B1 KR 101736033B1
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Abstract
Description
본 발명은 항비만 활성을 가지는 락토바실러스 사케아이에 관한 것이다. The present invention relates to Lactobacillus sakeae having anti-obesity activity.
인류가 풍요로운 사회로 발전함에 따라 비만이 심각한 질병으로 대두되고 있으며, 세계보건기구(WHO)에서는 비만을 치료해야 할 질병의 대상으로 명시하고 있다. 최근 우리나라에서도 서구화된 식습관에 따라 비만의 빈도가 증가하는 추세이며, 그 치료와 예방에 대한 관심이 높아지고 있다. As humanity develops into a rich society, obesity is becoming a serious disease, and the World Health Organization (WHO) specifies obesity as the target of diseases to be treated. In Korea, the frequency of obesity is increasing according to Westernized eating habits, and there is a growing interest in the treatment and prevention of obesity.
현재까지 알려진 비만 치료제로는 제니칼(Xenical, 로슈제약회사, 스위스), 리덕틸(Reductil, 에보트사, 미국) 및 엑소리제(Exolise, 아토파마, 프랑스) 등이 있다. 상기 비만 치료제는 크게 식욕억제제, 에너지소비 촉진제 또는 지방흡수억제제로 분류되는데, 대부분의 비만 치료제들은 시상하부와 관련된 신경전달물질을 조절함으로써 식욕을 억제하는 식욕억제제이다. 그러나 종래의 치료제들은 심장질환, 호흡기질환 및 신경계질환 등의 부작용을 초래하고 그 효능의 지속성도 낮으므로, 치료 효과가 개선된 비만치료제의 개발이 필요하다. 또한 부작용 없이 만족할만한 치료제는 없어 새로운 비만치료제의 개발이 요구된다. Currently known obesity treatments include Xenical (Roche Pharmaceuticals, Switzerland), Reductil (Evothe, USA) and Exolise (Atopama, France). The above-mentioned obesity treatment agents are classified largely into an appetite suppressant, an energy consumption promoter or a fat absorption inhibitor. Most of the obesity treatment agents are appetite suppressants that suppress the appetite by controlling the neurotransmitters associated with the hypothalamus. However, conventional therapeutic agents cause side effects such as heart diseases, respiratory diseases and nervous system diseases, and the persistence of the effects is low, so it is necessary to develop a therapeutic agent for obesity with improved therapeutic effect. In addition, there is no satisfactory treatment without side effects and development of new obesity treatment is required.
한편, 안전한 미생물로 여겨져 온 균류(예를 들어, 유산균)를 이용하여 비만을 예방 또는 치료하고자 하는 연구가 많이 진행되고 있다. 유산균은 장내 정상 균총의 유지, 장내 균총의 개선, 항당뇨 및 항지혈증 효과, 발암 억제, 대장암 억제, 및 숙주의 면역체계의 비특이적 활성 등의 효과를 가진다고 보고되고 있다. On the other hand, many studies have been conducted to prevent or treat obesity by using fungi (for example, lactic acid bacteria) that have been regarded as safe microorganisms. Lactic acid bacteria have been reported to have effects such as maintenance of intestinal microflora, improvement of intestinal flora, antidiabetic and antiproliferative effect, carcinogenesis inhibition, colorectal cancer suppression, and nonspecific activity of host immune system.
특히 김치로부터 분리한 유산균은 김치 발효에 관여하는 유산균으로써 먼역 증강, 항미생물 효과, 항산화 효과, 항암효과, 항비만 효과, 고혈압 예방 효과 및 변비 예방 효과 등이 있는 것으로 보고되고 있다(비특허문헌 1 내지 3).Especially, the lactic acid bacteria isolated from kimchi have been reported to have the effect of enhancing the kingdom, antimicrobial effect, antioxidant effect, anti-cancer effect, anti-obesity effect, hypertension prevention effect and constipation prevention effect as lactic acid bacteria involved in fermentation of kimchi (Non-Patent
현재까지 비만 예방 및 치료 효과와 관련된 유산균으로는, 락토바실러스 플란타룸(Lactobacillus plantarum) KY1032(제10-2012-0034482호, KCCM-10430), 락토바실러스 커베터스(Lactobacillus curvatus) HY7601(제10-0996577호, KCTC 11456BP), 락토바실러스 플란타룸(Lactobacillus plantarum) DSR920(제10-2013-0046896호, KCCM 11210P) 또는 락토바실러스 존소니(Lactobacillus johnsonii) HF1 108 균주(제10-2010-0010015호, KCTC 11356BP)가 있다. Lactobacillus plantarum KY1032 (10-2012-0034482, KCCM-10430), Lactobacillus curvatus HY7601 (10th-10th -0034482, KCCM-10430) -0996577, KCTC 11456BP), Lactobacillus plantarum DSR920 (10-2013-0046896, KCCM 11210P) or Lactobacillus johnsonii HF1 108 strain (No. 10-2010-0010015 , KCTC 11356BP).
그러나, 상업적으로 성공할 만큼 항비만 효과가 우수한 유산균 관련 기술은 출현하지 않았다. 따라서, 항비만 효과가 우수한 새로운 균주의 스크리닝 및 이의 다양한 기능을 규명할 필요가 있다.However, no commercially available lactic acid bacteria-related technology with excellent anti-obesity effect appeared. Therefore, screening of novel strains with excellent anti-obesity effect and their various functions need to be clarified.
본 발명은 락토바실러스 사케아이 WIKIM31(Lactobacillus sakei WIKIM31, KFCC11654P) 균주 및 그 이용에 관한 것으로, 지방세포 분화 억제 및 체지방 감소 효능을 가지는 락토바실러스 사케아이 균주를 제공하는 것을 목적으로 한다. The present invention relates to a strain of Lactobacillus sakei WIKIM31 (WIKIM31, KFCC11654P) and its use, and is intended to provide a lactobacillus skeeti strain having an effect of inhibiting adipocyte differentiation and reducing body fat.
본 발명에서는 지방세포 분화 억제 활성 및 체지방 감소 효능을 가지는 락토바실러스 사케아이 WIKIM31(Lactobacillus sakei WIKIM31, KFCC11654P) 균주를 제공한다. The present invention provides Lactobacillus sakei WIKIM31 and KFCC11654P strains having an activity of inhibiting adipocyte differentiation and reducing body fat.
또한, 본 발명에서는 전술한 균주, 이의 배양물, 이의 파쇄물 또는 이의 추출물을 포함하는 비만 또는 비만 관련 질환의 예방 또는 치료용 약학 조성물을 제공한다. In addition, the present invention provides a pharmaceutical composition for preventing or treating obesity or obesity-related diseases comprising the above-mentioned strains, a culture thereof, a crushed product thereof or an extract thereof.
또한, 본 발명에서는 전술한 균주, 이의 배양물, 이의 파쇄물 또는 이의 추출물을 포함하는 비만 또는 비만 관련 질환의 예방 또는 개선용 식품 조성물을 제공한다. The present invention also provides a food composition for preventing or ameliorating an obesity or obesity-related disease comprising the above-mentioned strain, a culture thereof, a crushed product thereof or an extract thereof.
본 발명에 따른 락토바실러스 사케아이 WIKIM31(Lactobacillus sakei WIKIM31, KFCC11654P) 균주는 3T3-L1 지방세포의 분화를 억제하여 지방 축적을 억제하고, 지방세포 분화에 관련된 유전자의 발현을 억제하여 체내 지방 축적을 억제함으로써, 체지방 감소 효과가 매우 뛰어나다. The Lactobacillus sakei WIKIM31 and KFCC11654P strains according to the present invention inhibit the differentiation of 3T3-L1 adipocytes, inhibit fat accumulation, inhibit the expression of genes involved in adipocyte differentiation, inhibit fat accumulation in the body The body fat reduction effect is very excellent.
따라서, 지방 대사에 영향을 미치는 약학적 조성물 및 기능성 식품 등으로 이용될 수 있다. Therefore, it can be used as a pharmaceutical composition and functional food affecting fat metabolism.
도 1은 균주 추출물의 처리에 따른 지방 축적량의 변화를 측정한 결과를 나타내는 사진 및 그래프이다.
도 2는 균주 추출물의 처리에 따른 지방세포 분화 및 전사관련 인자의 유전자 발현 변화를 측정한 결과를 나타내는 그래프이다.
도 3은 균주의 섭취에 따른 체중 변화를 측정한 결과를 나타내는 그래프이다.
도 4는 균주의 섭취에 따른 체중 증가량의 변화를 측정한 결과를 나타내는 표이다.
도 5는 균주의 섭취에 따른 지방 무게 및 체지방량의 변화를 측정한 결과를 나타내는 그래프이다.
도 6은 균주의 섭취에 따른 간 기능 수치의 변화를 측정한 결과를 나타내는 그래프이다.
도 7은 균주의 섭취에 따른 호르몬 변화를 측정한 결과를 나타내는 그래프이다. FIG. 1 is a photograph and a graph showing the results of measurement of changes in fat accumulation amount according to the treatment of the strain extract. FIG.
FIG. 2 is a graph showing the results of measurement of changes in gene expression of adipocyte differentiation and transcription-related factors upon treatment with a strain extract.
FIG. 3 is a graph showing a result of measuring a change in body weight according to ingestion of a strain. FIG.
FIG. 4 is a table showing the result of measuring the change in body weight gain with the ingestion of the strain.
FIG. 5 is a graph showing the results of measurement of changes in fat mass and body fat mass according to consumption of a strain.
FIG. 6 is a graph showing the results of measurement of changes in liver function values according to the ingestion of a strain. FIG.
FIG. 7 is a graph showing the results of measurement of hormone changes according to ingestion of a strain. FIG.
본 발명은 지방세포 분화 억제 활성 및 체지방 감소 효능을 가지는 락토바실러스 사케아이 WIKIM31(Lactobacillus sakei WIKIM31, KFCC11654P) 균주에 관한 것이다. The present invention relates to Lactobacillus sakei WIKIM31 and KFCC11654P strains having an adipocyte differentiation inhibiting activity and a body fat reducing effect.
본 발명에서 "배양물"이란 균주를 공지의 액체 배지 또는 고체 배지에서 배양시켜 수득한 산물을 의미하여, 균주를 포함하는 개념이다.In the present invention, the term "culture product" means a product obtained by culturing a strain in a known liquid medium or solid medium and includes a strain.
본 발명에서 "약학적으로 허용가능한" 및 "식품학적으로 허용가능한"이란 생물체를 상당히 자극하지 않고 투여 활성 물질의 생물학적 활성 및 특성을 저해하지 않는 것을 의미한다.The terms " pharmaceutically acceptable "and" pharmaceutically acceptable "in the present invention are intended to mean not significantly irritating the organism and not interfering with the biological activity and properties of the administered active substance.
본 발명에서 "예방"은 본 발명의 조성물의 투여로 특정 질환(예를 들어, 지방간)의 증상을 억제시키거나 진행을 지연시키는 모든 행위를 의미한다.In the present invention, "prevention" means any action that inhibits the symptoms of, or delays the progression of, a particular disease (e. G., Fatty liver) upon administration of the composition of the present invention.
본 발명에서 "치료"는 본 발명의 조성물의 투여로 특정 질환(예를 들어, 지방간)의 증상을 호전 또는 이롭게 변경시키는 모든 행위를 의미한다.In the present invention, "treatment" means any action that improves or alleviates the symptoms of a particular disease (e. G., Fatty liver) upon administration of the composition of the present invention.
본 발명에서 "개선"은 치료되는 상태와 관련된 파라미터, 예를 들면 증상의 정도를 적어도 감소시키는 모든 행위를 의미한다.In the present invention, "improvement" means all actions that at least reduce the degree of symptom associated with the condition being treated, for example.
본 발명에서 "투여"는 임의의 적절한 방법으로 개체에 소정의 본 발명의 조성물을 제공하는 것을 의미한다. 이때, 개체는 본 발명의 조성물을 투여하여 특정 질환의 증상이 호전될 수 있는 질환을 가진 인간, 원숭이, 개, 염소, 돼지 또는 쥐 등 모든 동물을 의미한다.In the present invention, "administration" means providing the desired composition of the present invention to an individual by any suitable method. The term " individual " means any animal such as a human, a monkey, a dog, a goat, a pig, or a mouse having a disease in which symptoms of a specific disease can be improved by administering the composition of the present invention.
또한, 본 발명에서 "약학적으로 유효한 양"은 의학적 치료에 적용 가능한 합리적인 수혜 또는 위험 비율로 질환을 치료하기에 충분한 양을 의미하며, 이는 개체의 질환의 종류, 중증도, 약물의 활성, 약물에 대한 민감도, 투여 시간, 투여 경로 및 배출비율, 치료기간, 동시에 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다.The term "pharmaceutically effective amount " in the present invention means an amount sufficient to treat a disease at a reasonable benefit or risk ratio applicable to medical treatment, and includes an amount of the disease of the individual, severity, activity of the drug, The drug's sensitivity, the time of administration, the route of administration and the rate of release, the duration of the treatment, factors including simultaneously used drugs, and other factors well known in the medical arts.
이하, 본 발명을 상세하게 설명한다. Hereinafter, the present invention will be described in detail.
본 발명에 따른 락토바실러스 사케아이 WIKIM31(Lactobacillus sakei WIKIM31, KFCC11654P) 균주(이하, WIKIM31 균주)는 지방세포 분화 억제 활성 및 체지방 감소 효능을 가진다. The Lactobacillus sakei WIKIM31 and KFCC11654P strains (hereinafter, referred to as WIKIM31 strains) according to the present invention have an adipocyte differentiation inhibiting activity and a body fat reducing effect.
상기 WIKIM31 균주는 16S rDNA로 서열번호 1에 기재된 염기서열을 포함할 수 있다. The WIKIM31 strain may contain the nucleotide sequence shown in SEQ ID NO: 1 as 16S rDNA.
본 발명에 따른 WIKIM31 균주는 김치, 예를 들어, 배추김치 또는 갓김치 등에서 분리될 수 있다.The strain WIKIM31 according to the present invention can be isolated from kimchi, for example, Chinese cabbage kimchi or mustard kimchi.
또한, 본 발명은 전술한 신규 균주인 WIKIM31 균주의 다양한 용도에 관한 것이다. The present invention also relates to the various uses of the novel strain WIKIM31 described above.
예를 들어, 본 발명에서는 WIKIM31 균주, 이의 배양물, 이의 파쇄물 또는 이의 추출물을 유효성분으로 포함하는 비만 또는 비만 관련 질환의 예방, 개선 또는 치료용 조성물을 제공한다. For example, the present invention provides a composition for preventing, ameliorating or treating obesity or obesity-related diseases comprising the WIKIM31 strain, a culture thereof, a crushed product thereof or an extract thereof as an active ingredient.
상기 배양물은 WIKIM31 균주 배지에서 배양시켜 수득한 산물로서, 상기 배지는 공지의 액체 배지 또는 고체 배지에서 선택될 수 있으며, 예를 들어 MRS 액체 배지, MRS 한천 배지일 수 있다. The culture is a product obtained by culturing in a WIKIM31 strain culture medium. The culture medium may be selected from known liquid culture media or solid culture media, for example, MRS liquid culture medium and MRS agar culture medium.
본 발명에 따른 WIKIM31 균주, 이의 배양물, 이의 파쇄물 또는 이의 추출물은 항비만 활성, 지방세포 분화 억제 활성 및 체지방 감소 효능 등과 같은 다양한 기능성을 가지기 때문에 비만 또는 비만 관련 질환을 예방, 개선 또는 치료하기 위한 유효성분으로 사용할 수 있다. 상기 비만 관련 질환은 비만에 의해 유발되거나 비만과 상관 관계가 높은 질환이라면 그 종류가 크게 제한되지 않으며, 예를 들어, 지방간, 제2형 당뇨, 고지혈증, 심혈관 질환, 동맥경화증 및 지질 관련 대사증후군 중에서 선택될 수 잇다. 또한, 상기 지질 관련 대사증후군은 당뇨, 비만 등 여러 가지 대사성 질환이 한 사람에게 동시에 나타나는 질환일 수 있다. The WIKIM31 strain, the culture thereof, the lysate thereof or the extract thereof according to the present invention has various functions such as anti-obesity activity, adipocyte differentiation inhibitory activity and body fat decreasing effect, so that it can prevent, ameliorate or treat obesity or obesity-related diseases It can be used as an active ingredient. The above-mentioned obesity-related diseases are not limited to those caused by obesity or those having a high correlation with obesity, for example, fatty liver,
또한, 본 발명에 따른 조성물은 비만 또는 비만 관련 질환의 예방, 개선 또는 치료 효과를 향상시키기 위하여, 락토바실러스 브레비스(Lactobacillus brevis), 락토바실러스 플란타룸(Lactobacillus plantarum), 락토바실러스 사케(Lactobacillus sake), 류코노스톡 메센테로이드(Leuconostoc mesenteroides) 및 바이셀라 코리엔시스(Weissella koreensis) 중에서 선택되는 하나 이상의 균주를 추가로 포함할 수 있다. In addition, the composition according to the present invention may be used in combination with Lactobacillus brevis , Lactobacillus plantarum , Lactobacillus sake , or the like to improve the preventive, ameliorative or therapeutic effect of obesity- , Leuconostoxesteroid ( Leuconostoc mesenteroides and Weissella < RTI ID = 0.0 > koreensis ). < / RTI >
또한, 본 발명의 비만 또는 비만 관련 질환의 예방, 개선 또는 치료용 조성물은 사용 목적 내지 양상에 따라 약학 조성물, 식품 첨가제, 식품 조성물(특히 기능성 식품 조성물), 또는 사료 첨가제 등으로 구체화될 수 있고, 조성물 내에서 유효성분인 WIKIM31 균주로 발효시킨 발효물의 함량도 조성물의 구체적인 형태, 사용 목적 내지 양상에 따라 다양한 범위에서 조정될 수 있다.The composition for preventing, ameliorating or treating obesity or obesity-related diseases of the present invention may be formulated into pharmaceutical compositions, food additives, food compositions (in particular, functional food compositions), feed additives or the like, The content of the fermented product fermented with the WIKIM31 strain as an active ingredient in the composition may be adjusted in various ranges depending on the specific form of the composition, the purpose of use, and the manner of use.
본 발명에 따른 비만 또는 비만 관련 질환의 예방 또는 치료용 약학 조성물에서 유효성분인 WIKIM31 균주, 이의 배양물, 이의 파쇄물 또는 이의 추출물의 함량은 크게 제한되지 않으며, 예를 들어 조성물 총 중량을 기준으로 0.01~99 중량%, 바람직하게는 0.5~50 중량%, 더 바람직하게는 1~30 중량%일 수 있다. In the pharmaceutical composition for preventing or treating obesity or obesity-related diseases according to the present invention, the content of the active ingredient WIKIM31 strain, the culture thereof, the lysate thereof or the extract thereof is not particularly limited and may be, for example, 0.01 To 99% by weight, preferably 0.5 to 50% by weight, more preferably 1 to 30% by weight.
본 발명에 따른 약학 조성물은 유효성분 외에 약학적으로 허용가능한 담체, 부형제 또는 희석제와 같은 첨가제를 더 포함할 수 있다. 본 발명의 약학 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다. 본 발명의 약학 조성물은 통상의 방법에 의해 경구 투여를 위한 제형 또는 비경구 투여를 위한 제형으로 제제화될 수 있고, 제제화할 경우 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제될 수 있다. 경구 투여를 위한 고형 제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형 제제는 유효성분에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트(Calcium carbonate), 수크로스(Sucrose), 락토오스(Lactose) 또는 젤라틴 등을 섞어 조제될 수 있다. 또한, 단순한 부형제 이외에 마그네슘 스티레이트 탈크 같은 윤활제들도 사용될 수 있다. 경구 투여를 위한 액상 제제로는 현탁제, 내용액제, 유제 및 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 좌제가 포함될 수 있다. 비수성용제, 현탁용제로는 프로필렌글리콜(Propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다. 더 나아가 당 분야의 적정한 방법으로 Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA에 개시되어 있는 방법을 이용하여 각 질환에 따라 또는 성분에 따라 바람직하게 제제화할 수 있다. 본 발명의 약학 조성물은 목적하는 방법에 따라 인간을 포함한 포유류에 경구 투여되거나 비경구 투여될 수 있으며, 비경구 투여 방식으로는 피부 외용, 복강내주사, 직장내주사, 피하주사, 정맥주사, 근육내 주사 또는 흉부내 주사 주입방식 등이 있다. 본 발명의 약학 조성물의 투여량은 약학적으로 유효한 양이라면 크게 제한되지 않으며, 환자의 체중, 연령, 성별, 건강상태, 식이, 투여시간, 투여방법, 배설율 및 질환의 중증도에 따라 그 범위가 다양하다. 본 발명의 약학 조성물의 통상적인 1일 투여량은 크게 제한되지 않으나 바람직하게는 유효성분을 기준으로 할 때 0.1 내지 3000 ㎎/㎏이고, 더 바람직하게는 1 내지 2000 ㎎/㎏이며, 하루 1회 또는 수회로 나누어 투여될 수 있다.The pharmaceutical composition according to the present invention may further comprise, in addition to the active ingredient, an additive such as a pharmaceutically acceptable carrier, excipient or diluent. Examples of carriers, excipients and diluents that can be included in the pharmaceutical composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate , Cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. The pharmaceutical composition of the present invention can be formulated into a formulation for oral administration or parenteral administration by a conventional method, and can be formulated into a pharmaceutical composition such as a filler, an extender, a binder, a wetting agent, a disintegrant, Diluents or excipients. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose ), Lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate talc may also be used. Liquid preparations for oral administration include suspensions, solutions, emulsions and syrups. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used. have. Formulations for parenteral administration may include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used as the non-aqueous solvent and suspension agent. As a base for suppositories, witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like can be used. Further, it can be suitably formulated according to each disease or ingredient, using the method disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA in a suitable manner in the art. The pharmaceutical composition of the present invention may be administered orally or parenterally to a mammal including a human according to a desired method. Examples of the parenteral administration method include external dermal application, intraperitoneal injection, intramuscular injection, subcutaneous injection, intravenous injection, Intravenous injection or intra-thoracic injection. The dosage of the pharmaceutical composition of the present invention is not limited as long as it is a pharmacologically effective amount and is not limited as long as it depends on the body weight, age, sex, health condition, diet, administration time, administration method, excretion rate, Varies. The typical daily dose of the pharmaceutical composition of the present invention is not particularly limited, but is preferably 0.1 to 3000 mg / kg, more preferably 1 to 2000 mg / kg, based on the active ingredient, once a day Or may be administered in divided doses.
또한, 본 발명의 비만 또는 비만 관련 질환의 예방 또는 개선용 식품 조성물에서 유효성분인 WIKIM31 균주, 이의 배양물, 이의 파쇄물 또는 이의 추출물의 함량은 조성물 총 중량을 기준으로 0.01~50 중량%, 바람직하게는 0.1~25 중량%, 더 바람직하게는 0.5~10 중량%이나, 이에 한정되는 것은 아니다. 본 발명의 식품 조성물은 환제, 분말, 과립, 침제, 정제, 캡슐, 또는 액제 등의 형태를 포함하며, 구체적인 식품의 예로는 육류, 소시지, 빵, 초콜릿, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 기능수, 드링크제, 알코올음료 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 건강식품을 모두 포함한다. 본 발명의 식품 조성물은 유효성분 외에 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 또한, 본 발명의 식품 조성물은 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그 밖에 본 발명의 식품 조성물은 천연 과일주스, 과일주스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분들은 독립적으로 또는 혼합하여 사용할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드, 말토스, 슈크로스와 같은 디사카라이드, 및 덱스트린, 사이클로덱스트린과 같은 폴리사카라이드, 자일리톨, 소르비톨, 에리트리톨 등의 당알코올이다. 향미제로는 타우마틴, 스테비아 추출물과 같은 천연 향미제나 사카린, 아스파르탐과 같은 합성 향미제 등을 사용할 수 있다.In the food composition for preventing or ameliorating obesity or obesity-related diseases according to the present invention, the content of the active ingredient WIKIM31 strain, the culture thereof, the lysate thereof or the extract thereof is 0.01 to 50% by weight, Is 0.1 to 25% by weight, more preferably 0.5 to 10% by weight, but is not limited thereto. The food composition of the present invention may be in the form of a pill, a powder, a granule, an infusion, a tablet, a capsule, or a liquid preparation. Examples of the food include meat, sausage, bread, chocolate, candy, snack, Other noodles, gums, dairy products including ice cream, various soups, drinks, tea, functional water, drinks, alcoholic beverages and vitamin complexes. The food composition of the present invention may contain various flavors or natural carbohydrates as an additional ingredient in addition to the active ingredient. In addition, the food composition of the present invention can be used as a food composition containing various nutrients, vitamins, electrolytes, flavors, colorants, pectic acids and salts thereof, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, , A carbonating agent used in carbonated drinks, and the like. In addition, the food composition of the present invention may contain flesh for the production of natural fruit juices, fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The above-mentioned natural carbohydrates are sugar alcohols such as monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and xylitol, sorbitol and erythritol. Natural flavors such as tau Martin and stevia extract, and synthetic flavors such as saccharin and aspartame may be used as the flavor.
이하, 본 발명의 이해를 돕기 위하여 실시예 등을 들어 상세하게 설명하기로 한다. 그러나, 본 발명에 따른 실시예들은 여러 가지 다른 형태로 변형될 수 있으며, 본 발명의 범위가 하기 실시예들에 한정되는 것으로 해석돼서는 안 된다. 본 발명의 실시예들은 당 업계에서 평균적인 지식을 가진 자에게 본 발명을 보다 완전하게 설명하기 위해 제공되는 것이다.Hereinafter, embodiments of the present invention will be described in detail to facilitate understanding of the present invention. However, the embodiments according to the present invention can be modified into various other forms, and the scope of the present invention should not be construed as being limited to the following embodiments. Embodiments of the invention are provided to more fully describe the present invention to those skilled in the art.
실시예Example
1. 균주 분리, 배양 추출물 제조 1. Isolation of strain, production of culture extract
균주는 강원도의 가정집에서 배추 김치를 수집한 후, 김치 유산균을 분리하였다. The strains were harvested from a domestic home in Gangwon - do, and Kimchi lactic acid bacteria were isolated.
수집된 김치 시료를 파쇄하고 여과한 후, 106 내지 109의 배율로 희석하여 Lactobacilli MRS(Difco) agar 배지에 도말 후, 24시간 이상 배양하였다. 배양 후 형성된 콜로니의 형태를 비교하고 각기 다른 유산균을 선별 및 배양하여 지방세포 분화과정에서 지방 축적 실험을 통하여 스크리닝한 후, 16S RNA 염기서열 분석을 통하여 최종적으로 동정하였다. 그 중 효과가 뛰어난 1종의 유산균을 세계김치연구소 미생물 유전자 은행으로부터 WIKIM31의 고유번호를 부여받아 락토바실러스 사케아이 WIKIM31(Lactobacillus sakei WIKIM31)이라 명명하였다. The collected kimchi samples were crushed, filtered, diluted at a magnification of 10 6 to 10 9 , plated on Lactobacilli MRS (Difco) agar medium, and cultured for 24 hours or more. After colony formation, cultured lactic acid bacteria were selected and cultured. The cells were screened for lipid accumulation during adipocyte differentiation and finally identified by 16S RNA sequencing. Among them, one kind of lactic acid bacteria having excellent effect was named LIKE Lactobacillus sakei WIKIM31 by giving the unique number of WIKIM31 from the Kimchi Institute Microbiology Gene Bank of the world.
균주 추출물은 MRS 배지에서 30℃ 및 24 시간 동안 배양한 후, 균체를 12,000 rpm에서 10분 동안 원심분리한 후 PBS(Phosphate buffered saline)로 헹궈서 남아있는 배지 성분을 제거하고, 균체를 1×109 CFU/ml의 농도로 resuspension한 후 FastPrep-24ⓡ sample preparation system(MP Biomedicals, CA, USA)을 이용하여 균체를 lysis하였다. 이를 12,000 rpm에서 10분 동안 원심분리한 후 상등액을 이용하여 실험에 사용하였다.The strain extracts were cultured in MRS medium at 30 ° C. for 24 hours. The cells were centrifuged at 12,000 rpm for 10 minutes and rinsed with PBS (phosphate buffered saline) to remove the remaining medium. The cells were washed with 1 × 10 9 after resuspension in a concentration of CFU / ml using a FastPrep-24 ⓡ sample preparation system ( MP Biomedicals, CA, USA) was lysis the cells. This was centrifuged at 12,000 rpm for 10 minutes and then used in the supernatant.
실험결과는 평균(mean) 표준편차(SD)로 나타내었고 통계적 유의성은 SPSS 18.0 프로그램을 이용하여 검정하였으며, One-way ANOVA의 Duncan’s multiple range test를 이용하여 그룹간의 차이를 통계처리한 후, p<0.05 수준에서 유의성을 검정하였다. Statistical analysis was performed using the SPSS 18.0 program. Statistical analysis was performed using the Duncan's multiple range test of the one-way ANOVA. The significance was tested at 0.05 level.
2. 지방세포 분화과정에서 지방 축적(lipid accumulation) 측정 2. Measurement of lipid accumulation during adipocyte differentiation
락토바실러스 사케아이 WIKIM31(Lactobacillus sakei WIKIM31) 추출물이 지방분화과정에서 지방축적 정도에 미치는 효과를 알아보기 위해 Negrel과 Dani의 방법에 따라 Oil Red O 염색을 실시하였다. To determine the effect of Lactobacillus sakei WIKIM31 extract on fat accumulation in lipid differentiation, Oil Red O staining was performed according to the method of Negrel and Dani.
100% confluent stage 2일 후, adipogenic cocktail 첨가 배양액, 인슐린 첨가 배양액, FBS 배양액으로 교환시 균주 추출물 1.0 X108 CFU/ml의 농도로 처리하였으며, 9일의 분화 후 배양액을 제거하고 PBS로 세척한 다음 10% 포름알데히드로 10분간 고정시켰다. 10% 포름알데히드를 제거하고 다시 포화된 포름알데히드를 넣어 1시간 이상 세포를 고정시켰다. 그 후 60% 이소프로판올을 넣고 바로 제거한 후 증류수로 세척하고 Oil red O 염색용액으로 30 분간 지방구를 염색한 후 증류수로 세척하였다. 염색된 지방구의 세포 내 지방축적을 현미경을 이용하여 관찰하였으며 사진촬영을 통해 육안적으로 균주 추출물이 자방 분화시 지방축적에 미치는 영향을 관찰하였다. 축적된 지방 확인을 위해 잘 건조된 상태에서 isopropanol 을 첨가하여 Oil red O dye를 용출한 뒤 multi-plate reader 를 사용하여 500 nm에서 흡광도를 측정하였다. After 2 days of 100% confluent stage, the cells were treated with 1.0 × 10 8 CFU / ml of strain extract at the time of replacement with adipogenic cocktail, insulin and FBS cultures. After 9 days of differentiation, the culture broth was removed and washed with PBS And fixed with 10% formaldehyde for 10 minutes. 10% formaldehyde was removed and the cells were fixed for more than 1 hour by adding saturated formaldehyde again. After that, 60% isopropanol was added to the flask. The flask was washed with distilled water, stained with oil red O staining solution for 30 minutes, and washed with distilled water. The intracellular fat accumulation of dyed lipids was observed using a microscope and the effect of the extract of the strains on lipid accumulation was observed visually. To confirm the accumulation of fat, isopropanol was added to the dried oil to elute the oil red O dye, and the absorbance was measured at 500 nm using a multi-plate reader.
본 발명에서 도 1은 락토바실러스 사케아이 WIKIM31(Lactobacillus sakei WIKIM31) 추출물의 처리에 따른 지방 축적량을 측정한 결과를 나타내는 사진 및 그래프이다. 도 1에서 정상군(normal)은 전구지방세포에 분화유도를 하지 않은 미분화지방세포를, 대조군(control)은 완전히 분화된 지방세포(differentiated adipocytes)를 의미한다. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a photograph and a graph showing the result of measurement of fat accumulation by treatment with Lactobacillus sakei WIKIM31 extract of Lactobacillus sakei WIKIM31. In FIG. 1, the normal group refers to undifferentiated adipocytes that do not induce differentiation into precursor adipocytes, and the control refers to completely differentiated adipocytes.
분화된 지방세포층은 Oil red O로 염색하고 촬영하였다. 상기 (a)는 촬영 사진이며, (b)는 microscope 및 photographed (100 X magnification)를 사용하여 촬영한 사진으로 형태학적 변화를 관찰할 수 있다. 또한, (C)는 정량한 지질 함량(lipid content)을 나타내는 그래프이다. The differentiated adipocyte layer was stained with Oil red O and photographed. (A) is a photographic image, and (b) is a photographic image obtained by using a microscope and photographed (100 X magnification). In addition, (C) is a graph showing a quantified lipid content.
WIKIM31 추출물의 처리한 경우, 균주 추출물을 사용하지 않은 분화된 지방세포(대조군)와 비교했을 때, 지질 함량이 10% 농도에서 유의적으로 감소하는 효과를 나타냈다(도 1 참조). 따라서 본 발명에 따른 락토바실러스 사케아이 WIKIM31(Lactobacillus sakei WIKIM31) 추출물은 항비만 효과 및 체지방감소 효과가 있을 것으로 사료된다. When treated with WIKIM31 extract, lipid content was significantly reduced at 10% concentration (see FIG. 1) when compared to the differentiated fat cells without the strain extract (control group). Therefore, the extract of Lactobacillus sakei WIKIM31 according to the present invention is expected to have an anti-obesity effect and a body fat reduction effect.
또한, 본 발명에서 도 2는 균주 추출물 처리에 따른 3T3-L1 전지방세포(pre-adipocytes)의 지방세포 분화 및 전사관련 인자의 유전자를 측정한 결과를 나타내는 그래프이다.2 is a graph showing the results of measuring the adipocyte differentiation and transcription-related factors of 3T3-L1 pre-adipocytes according to the strain extract treatment.
지방세포로 분화 단계에서 PPAR-γ(Peroxisome proliferator-activated receptor-γ), C/EBP-α(CCAAT/enhancer binding protein-α), SREBP-1c(Sterol regulatory element-binding protein-1c), aP2α(activator protein 2 alpha), FAS(Fatty acid synthase) 및 GLUT4(Glucose transporter type 4)의 발현은 증가한다. (PPAR-γ), C / EBP-α (CCAAT / enhancer binding protein-α), SREBP-1c (sirtol regulatory element-binding protein-1c) and
지방세포 분화 유도 방법과 같이 균주 추출물 1.0 X108 CFU/ml 농도로 처리한 후 9일 동안 분화시켜, 지방세포의 분화에 관련하는 유전자들의 발현 정도를 확인하기 위하여 PCR(Real time quantitative)을 실시하였다. 지방세포의 Total RNA는 Trizol reagent (Invitrogen, Carlsbad, CA)를 사용하여 분리하였다. 각각의 분리된 RNA 1 ng을 TOPscriptTM cDNA Synthesis kit (Enzynomics, Daejeon, Korea)와 S1000 Thermal Cycler (Bio-Rad, USA)를 사용하여 cDNA를 합성하였다. 합성된 cDNA를 각각의 primer, nuclease-free water, TOPrealTM qPCR 2x PreMIX (SYBR Green)과 프라이머(primer)를 넣고 BioRad CFX-96 real time system (BioRad)을 이용하여 증폭하였다. 대조군 유전자로는 β-actin primer를 사용하였다.As a method of inducing adipocyte differentiation, the strain was treated with a concentration of 1.0 × 10 8 CFU / ml, and then differentiated for 9 days. In order to confirm the expression level of the genes involved in adipocyte differentiation, PCR (Real time quantitative) was performed . Total RNA of adipocytes was isolated using Trizol reagent (Invitrogen, Carlsbad, Calif.). 1 ng of each separated RNA was synthesized using TOPscript TM cDNA synthesis kit (Enzynomics, Daejeon, Korea) and S1000 Thermal Cycler (Bio-Rad, USA). The synthesized cDNA was amplified using BioRad CFX-96 real time system (BioRad) with primers, nuclease-free water, TOPreal ™ qPCR 2x PreMIX (SYBR Green) and primers. As a control gene, β-actin primer was used.
상기 도 2에 나타나듯이, 균주 추출물의 처리에 따라 지방세포 분화관련 인자인 (A) PPARγ (B) C/EBPα, (C) SREBP-1c, (D) aP2α, (E) FAS 및 (F) GLUT4의 유전자 발현이 감소하는 것을 확인할 수 있다.(A) PPARγ (B) C / EBPα, (C) SREBP-1c, (D) aP2α, (E) FAS and (F) It is confirmed that the expression of GLUT4 gene is decreased.
3. 체중 감소 효능 측정 3. Measurement of weight loss efficacy
4주령 수컷 C57BL/6J mice를 온도 20±2℃, 습도 50±5% 및 명암 주기(light-dark cycle) 12시간 단위의 사육실 환경하에서 chow diet(CD; Purina, Korea)로 1주간 적응시켰다. 이후, 실험동물을 2개의 그룹으로 나누어 정상 식이군(Normal, n=6)은 AIN-76 semipurified diet 조성에 준하여 조제하고(Corn oil, 5% wt.wt), 고지방 식이군(n=6)에는 총 칼로리의 45%가 지방인 고지방 식이(D12451, Research Diets, New Brunswick, NJ)를 10주간 공급하여 비만을 유도하였다. 1주동안 고지방 식이로 적응시킨 후, 고지방 식이군을 6마리씩 2개의 그룹(HFD, HFD+WIKIM31)으로 나눈 후, HFD군에는 고지방 식이를 공급함과 동시에 인산완충식염수(phosphate buffered saline, PBS)를 10주간 경구투여하였고, HFD+WIKIM31군에는 고지방 식이를 공급함과 동시에 락토바실러스 사케아이 WIKIM31(Lactobacillus sakei WIKIM31)을 인산완충식염수(phosphate buffered saline, PBS)에 현탁하여 10주간 경구투여하였다. 또한, 정상 식이군(Normal)에는 일반 식이를 공급함과 동시에 HFD군과 동일한 양의 인산완충식염수(phosphate buffered saline, PBS)를 5주간 경구투여하였다. 이때, WIKIM31은 매일 1×109 CFU/200ul/day의 농도로 경구투여 하였다.Four-week-old male C57BL / 6J mice were adapted to chow diet (CD; Purina, Korea) for 1 week under a temperature of 20 ± 2 ° C, a humidity of 50 ± 5% and a light- The animals were divided into two groups: normal (n = 6), corn oil (5% wt.wt), high fat diet (n = 6) (D12451, Research Diets, New Brunswick, NJ) were fed for 10 weeks, and 45% of total calories were fed a fat diet. After high fat diet for 1 week, high fat diet group was divided into two groups (HFD, HFD + WIKIM31) by 6 groups. The HFD group was fed with high fat diets and phosphate buffered saline (PBS) (HFD + WIKIM31) was fed a high fat diet, and Lactobacillus sakei WIKIM31 was suspended in phosphate buffered saline (PBS) for 10 weeks. In addition, a normal diet was fed with a normal diet and the same amount of phosphate buffered saline (PBS) as in the HFD group was orally administered for 5 weeks. At this time, WIKIM31 was orally administered at a concentration of 1 × 10 9 CFU / 200 μl / day on a daily basis.
10주 후, 균주 섭취로 인한 마우스의 체중 변화를 확인하였다. After 10 weeks, the mice were observed for weight change due to the strain ingestion.
본 발명에서 도 3은 마우스의 10주 동안의 체중 변화를 나타내는 그래프이고, 도 4는 10주 동안의 체중 증가량을 측정한 표이다. 3 is a graph showing changes in body weight during a 10-week period in a mouse, and FIG. 4 is a chart showing a weight increase during a 10-week period.
상기 도 3 및 도 4에 나타난 바와 같이, WIKIM31을 투여할 경우(HFD+WIKIM31) 고지방식이 섭취 마우스(HFD)와 비교하여 체중이 유의적으로 감소하며, 체중 증가량 또한, 감소하는 것을 확인할 수 있다.As shown in FIG. 3 and FIG. 4, when WIKIM31 was administered (HFD + WIKIM31), the body weight of the high fat diet was significantly decreased and the body weight increase was also decreased compared with the intake high fat diet (HFD) .
4. 지방조직 무게 변화 측정 4. Measurement of fat tissue weight change
3.의 방법으로, 10 주 동안 비만을 유도하면서 WIKIM31을 투여한 살아있는 마우스의 체성분 분석을 위하여 EchoMRITM-500 Body Composition Analyzer를 이용하여 총 체지방(Total body fat)을 측정하였다.Total body fat was measured using an EchoMRI ™ -500 Body Composition Analyzer for body composition analysis of live mice that received WIKIM31, inducing obesity for 10 weeks.
실험동물의 부고환 지방조직(epididymal fat), 복부 지방조직(abdominal fat)은 실험 종료 시에 적출하여 생리 식염수에 세척하고, 여과지에 수분을 제거한 후, 중량을 측정하였다.The epididymal fat and the abdominal fat of the experimental animals were removed at the end of the experiment, washed with physiological saline, and the water was removed from the filter paper and then weighed.
본 발명에서 도 5는 지방 무게 및 체지방량을 측정한 결과를 나타내는 그래프이다. FIG. 5 is a graph showing the results of measurement of fat weight and body fat mass in the present invention.
상기 도 5에 나타난 바와 같이, WIKIM31을 투여할 경우(HFD+WIKIM31) 고지방식이 섭취 마우스(HFD)와 비교하여 부고환 지방조직(epididymal fat) 및 복부 지방조직(abdominal fat)과 같은 지방 무게가 감소하며, 이에 따라 체지방량이 감소하는 것을 확인할 수 있다.As shown in FIG. 5, when the WIKIM31 was administered (HFD + WIKIM31), the high fat diet showed a decrease in fat weight such as epididymal fat and abdominal fat compared with the intake mice (HFD) And thus it can be confirmed that the amount of body fat is reduced.
5. 혈액 중의 GOT, GPT 측정 5. Measurement of GOT and GPT in blood
3.의 방법으로, 10 주 동안 비만을 유도하면서 WIKIM31을 투여한 마우스를 실험 종료 전에 24시간 절식시킨 다음, 복강대정맥에서 채혈하였으며, 혈청을 분리하여 실험에 사용하였다. 혈액 중의 GOT(glutamic oxaloacetic transaminase) 및 GPT(glutamic-pyruvic transaminase) 농도는 자동 생화학 측정기(FUJI DRI-CHEM 7000i, Fujifilm, Tokyo, Japan)를 이용하여 측정하였다.Using the method of 3., the mice receiving WIKIM31 inducing obesity for 10 weeks were fasted for 24 hours before the end of the experiment, and then blood was collected from the abdominal vena cava and serum was separated and used for the experiment. Glutamic oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) concentrations in the blood were measured using an automated biochemical analyzer (FUJI DRI-CHEM 7000i, Fujifilm, Tokyo, Japan).
본 발명에서 도 6은 균주 섭취에 따른 GOT 및 GPT 의 농도 변화를 나타내는 그래프이다. FIG. 6 is a graph showing changes in the concentrations of GOT and GPT according to the strain ingestion.
상기 도 6에 나타난 바와 같이, WIKIM31을 투여할 경우(HFD+WIKIM31) 고지방식이 섭취 마우스(HFD)와 비교하여 GOT 및 GPT 의 농도가 유의적으로 감소하는 것을 확인할 수 있다. 특히, HFD+WIKIM31에서 GOT 및 GPT 모두 정상 식이군(Normal) 보다 더 감소된 농도를 보이므로, 본 발명에 따른 균주, 즉 WIKIM31이 간 기능 개선에 매우 효과적임을 확인할 수 있다. As shown in FIG. 6, when WIKIM31 was administered (HFD + WIKIM31), it was confirmed that the GOT and GPT concentrations were significantly decreased compared to the high-fat diet fed mice (HFD). In particular, since the concentration of GOT and GPT in HFD + WIKIM31 is lower than that in the normal diet group, it can be confirmed that the strain according to the present invention, namely WIKIM31, is highly effective in improving liver function.
6. 혈중 호르몬 변화 측정 6. Measurement of blood hormone changes
3.의 방법으로, 10 주 동안 비만을 유도하면서 WIKIM31을 투여한 마우스의 혈청을 이용하여, 혈중 호르몬 변화를 측정하였다. 혈중 호르몬은 Bio-plex diabetes assay plex(Bio-rad)를 사용하여 Bio-plex MAGPIXTM Multiplex Reader에서 측정하였다.Using the method of 3., the serum of the mice to which WIKIM31 was administered with induction of obesity for 10 weeks was used to measure changes in blood hormones. Serum hormones were measured on a Bio-plex MAGPIX ™ Multiplex Reader using a Bio-plex diabetes assay plex (Bio-rad).
Leptin, 플라즈미노겐 활성인자 억제자-1(PAI-1), resistin은 체내 지방조직이 증가함에 따라, 혈중 농도가 증가한다.Leptin, plasminogen activator inhibitor-1 (PAI-1), and resistin increase in blood levels as the body fat tissue increases.
본 발명에서 도 7은 균주 섭취에 따른 호르몬 변화를 측정한 결과를 나타내는 그래프이다.FIG. 7 is a graph showing the results of measuring the hormone changes according to the strain ingestion.
상기 도 7에 나타난 바와 같이, WIKIM31을 투여할 경우(HFD+WIKIM31) 고지방식이 섭취 마우스(HFD)와 비교하여 혈중 호르몬인 Leptin, PAI-1 및 Resistin의 농도가 유의적으로 감소한 것을 확인할 수 있다. As shown in FIG. 7, when the WIKIM31 was administered (HFD + WIKIM31), the blood levels of Leptin, PAI-1 and Resistin, which are hormones in the blood, were significantly decreased compared with the fed mice (HFD) .
기탁기관명: 한국미생물보존센터(국내)Name of depository: Korea Microorganism Conservation Center (Domestic)
수탁번호: KFCC11654PAccession number: KFCC11654P
수탁일자: 2016. 3. 4Deposit date: March 3, 2016
<110> Korea Food Research Institute <120> Lactobacillus sakei with activity of anti-obesity <130> P15R10C1843 <160> 1 <170> KopatentIn 2.0 <210> 1 <211> 1518 <212> RNA <213> Lactobacillus sakei WIKIM31 <400> 1 ctcaggttga acgctgggcg cgtgcctaat aacagcaagt cgaacgcact ctcgtttaga 60 ttgaaggagc ttgcttctga ttgattaaca tttgagtgag tggcggacgg gtgagtaaca 120 cgtgggtaac ctgccctaaa gtgggggata acatttggaa acagatgcta ataccgcata 180 aaacctaaca ccgcatggtg tagggttgaa agatggtttc ggctatcact ttaggatgga 240 cccgcggtgc attagttagt tggtgaggta aaggctcacc aagaccgtga tgcatagccg 300 acctgagagg gtaatcggcc acactgggac tgagacacgg cccagactcc tacgggaggc 360 agcagtaggg aatcttccac aatggacgaa agtctgatgg agcaacgccg cgtgagtgaa 420 gaaggttttc ggatcgtaaa actctgttgt tggagaagaa tgtatctgat agtaactgat 480 caggtagtga cggtatccaa ccagaaagcc acggctaact acgtgccagc agccgcggta 540 atacgtaggt ggcaagcgtt gtccggattt attgggcgta aagcgagcgc aggcggtttc 600 ttaagtctga tgtgaaagcc ttcggctcaa ccgaagaagt gcatcggaaa ctgggaaact 660 tgagtgcaga agaggacagt ggaactccat gtgtagcggt gaaatgcgta gatatatgga 720 agaacaccag tggcgaaggc ggctgtctgg tctgtaactg acgctgaggc tcgaaagcat 780 gggtagcaaa caggattaga taccctggta gtccatgccg taaacgatga gtgctaggtg 840 ttggagggtt tccgcccttc agtgccgcag ctaacgcatt aagcactccg cctggggagt 900 acgaccgcaa ggttgaaact caaaggaatt gacgggggcc cgcacaagcg gtggagcatg 960 tggtttaatt cgaagcaacg cgaagaacct taccaggtct tgacatcctt tgaccactct 1020 agagatagag ctttcccttc ggggacaaag tgacaggtgg tgcatggttg tcgtcagctc 1080 gtgtcgtgag atgttgggtt aagtcccgca acgagcgcaa cccttattac tagttgccag 1140 catttagttg ggcactctag tgagactgcc ggtgacaaac cggaggaagg tggggacgac 1200 gtcaaatcat catgcccctt atgacctggg ctacacacgt gctacaatgg atggtacaac 1260 gagttgcgag accgcgaggt ttagctaatc tcttaaaacc attctcagtt cggattgtag 1320 gctgcaactc gcctacatga agccggaatc gctagtaatc gcggatcagc atgccgcggt 1380 gaatacgttc ccgggccttg tacacaccgc ccgtcacacc atgagagttt gtaacaccca 1440 aagccggtga ggtaaccctt cggggagcca gccgtctaag gtgggacaga tgattagggt 1500 gaagtcgtac aggggaaa 1518 <110> Korea Food Research Institute <120> Lactobacillus sakei with activity of anti-obesity <130> P15R10C1843 <160> 1 <170> Kopatentin 2.0 <210> 1 <211> 1518 <212> RNA <213> Lactobacillus sakei WIKIM31 <400> 1 ctcaggttga acgctgggcg cgtgcctaat aacagcaagt cgaacgcact ctcgtttaga 60 ttgaaggagc ttgcttctga ttgattaaca tttgagtgag tggcggacgg gtgagtaaca 120 cgtgggtaac ctgccctaaa gtgggggata acatttggaa acagatgcta ataccgcata 180 aaacctaaca ccgcatggtg tagggttgaa agatggtttc ggctatcact ttaggatgga 240 cccgcggtgc attagttagt tggtgaggta aaggctcacc aagaccgtga tgcatagccg 300 acctgagagg gtaatcggcc acactgggac tgagacacgg cccagactcc tacgggaggc 360 agcagtaggg aatcttccac aatggacgaa agtctgatgg agcaacgccg cgtgagtgaa 420 gaaggttttc ggatcgtaaa actctgttgt tggagaagaa tgtatctgat agtaactgat 480 caggtagtga cggtatccaa ccagaaagcc acggctaact acgtgccagc agccgcggta 540 atacgtaggt ggcaagcgtt gtccggattt attgggcgta aagcgagcgc aggcggtttc 600 ttaagtctga tgtgaaagcc ttcggctcaa ccgaagaagt gcatcggaaa ctgggaaact 660 tgagtgcaga agaggacagt ggaactccat gtgtagcggt gaaatgcgta gatatatgga 720 agaacaccag tggcgaaggc ggctgtctgg tctgtaactg acgctgaggc tcgaaagcat 780 gggtagcaaa caggattaga taccctggta gtccatgccg taaacgatga gtgctaggtg 840 ttggagggtt tccgcccttc agtgccgcag ctaacgcatt aagcactccg cctggggagt 900 acgaccgcaa ggttgaaact caaaggaatt gacgggggcc cgcacaagcg gtggagcatg 960 tggtttaatt cgaagcaacg cgaagaacct taccaggtct tgacatcctt tgaccactct 1020 agagatagag ctttcccttc ggggacaaag tgacaggtgg tgcatggttg tcgtcagctc 1080 gtgtcgtgag atgttgggtt aagtcccgca acgagcgcaa cccttattac tagttgccag 1140 catttagttg ggcactctag tgagactgcc ggtgacaaac cggaggaagg tggggacgac 1200 gtcaaatcat catgcccctt atgacctggg ctacacacgt gctacaatgg atggtacaac 1260 gagttgcgag accgcgaggt ttagctaatc tcttaaaacc attctcagtt cggattgtag 1320 gctgcaactc gcctacatga agccggaatc gctagtaatc gcggatcagc atgccgcggt 1380 gaatacgttc ccgggccttg tacacaccgc ccgtcacacc atgagagttt gtaacaccca 1440 aagccggtga ggtaaccctt cggggagcca gccgtctaag gtgggacaga tgattagggt 1500 gaagtcgtac aggggaaa 1518
Claims (6)
Lactobacillus sakei WIKIM31 (KFCC11654P) strain having an activity of inhibiting adipocyte differentiation and having a body fat reducing effect.
김치로부터 분리된 것인 락토바실러스 사케아이 WIKIM31(Lactobacillus sakei WIKIM31, KFCC11654P) 균주.
The method according to claim 1,
Lactobacillus sakei WIKIM31, KFCC11654P) strain isolated from kimchi.
A pharmaceutical composition for preventing or treating obesity, fatty liver, type 2 diabetes, hyperlipidemia, cardiovascular disease, arteriosclerosis or lipid-related metabolic syndrome comprising the strain according to claim 1, a culture thereof, a crushed product thereof or an extract thereof.
락토바실러스 브레비스(Lactobacillus brevis), 락토바실러스 플란타룸(Lactobacillus plantarum), 락토바실러스 사케(Lactobacillus sake), 류코노스톡 메센테로이드(Leuconostoc mesenteroides) 및 바이셀라 코리엔시스(Weissella koreensis) 중에서 선택되는 하나 이상의 균주를 추가로 포함하는 약학 조성물.
The method of claim 3,
Lactobacillus brevis , Lactobacillus plantarum , Lactobacillus sake , Leuconostocensenteroids ( Leuconostoc mesenteroides , and Weissella koreensis . < RTI ID = 0.0 > 21. < / RTI >
A food composition for preventing or ameliorating an obesity, fatty liver, type 2 diabetes, hyperlipidemia, cardiovascular disease, arteriosclerosis or lipid-related metabolic syndrome comprising the strain according to claim 1, a culture thereof, a crushed product thereof or an extract thereof.
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