J Korean Soc Food Sci Nutr 한국식품영양과학회지 43(1), 1484~149(214) http://dx.doi.org/1.3746/jkfn.214.43.1.1484 Lactobacillus plantarum CECT 7527, 7528, 7529 혼합물이고지방식이를급여한흰쥐의비만및지질대사에미치는영향 김대환 1 최미란 1 홍지은 1 이재용 1,2 이순임 3 정수환 3 김은지 1 1 한림대학교식의약품의효능평가및기능성소재개발센터 2 한림대학교의과대학생화학교실 3 한올바이오파마주식회사개발팀 Effect of Mixture of Lactobacillus plantarum CECT 7527, 7528, and 7529 on Obesity and Lipid Metabolism in Rats Fed a High-fat Diet Dae Hwan Kim 1, Mi-Ran Choi 1, Ji Eun Hong 1, Jae-Yong Lee 1,2, Soon Im Lee 3, Su Hwan Jung 3, and Eun Ji Kim 1 1 Center for Efficacy Assessment and Development of Functional Foods and Drugs and 2 Department of Biochemistry, College of Medicine, Hallym University 3 Business Development Department, HanAll BioPharma Co. Ltd. ABSTRACT In the present study, we examined the effects of a mixture of three strains, Lactobacillus plantarum CECT 7527, 7528, and 7529 (L. plantarum mixture), on body weight and lipid metabolism in Sprague-Dawley rats fed a high-fat diet. Rats were fed a high-fat diet and subjected to oral gavage with vehicle or the L. plantarum mixture (.6 1 9, 1.2 1 9, 2.4 1 9 colony-forming units (CFU)/day/rat, respectively) for 8 weeks. In rats fed a high-fat diet, oral administration of 2.4 1 9 CFU/day of the L. plantarum mixture significantly reduced body weight gain as well as weights of liver and epididymal fat. Leptin levels in sera were significantly reduced by oral administration of 2.4 1 9 CFU/day of the L. plantarum mixture. The L. plantarum mixture (1.2 1 9 or 2.4 1 9 CFU/day) also reduced the concentrations of total cholesterol and LDL-cholesterol in sera when it administered orally. Further, the L. plantarum mixture significantly reduced the atherogenic index and cardiac risk factor. In addition, oral administration of 2.4 1 9 CFU/day of the L. plantarum mixture markedly reduced levels of total lipids, triglycerides, and total cholesterol in the liver. The results of this study indicate that the L. plantarum mixture may exhibit anti-obesity and cholesterol-lowering effects, which suggest that the L. plantarum mixture has the potential to be a probiotic in the management of obesity and hypercholesterolemia. Key words: Lactobacillus plantarum mixture, antiobesity effect, hypocholesterolemic effect, high-fat diet 서 식생활의서구화와가공식품소비의증가에따라동물성식품및지방의섭취가증가하여이와관련된여러질병의발생빈도가높아지고있다. 우리나라국민의총에너지섭취량중지방에너지섭취비율은 1982년에 9.6% 에서 212 년에는 19.6% 로증가하였고, 212년에는에너지 / 지방과잉섭취자분율이 7.7% 로나타났다 (1). 지방섭취증가는체내당질및지질대사에이상을초래하여비만및고지혈증을유발하고, 이는동맥경화와심근경색등심혈관 순환기질환의위험인자로작용한다 (2). 현재세계적으로비만및 Received 22 May 214; Accepted 16 July 214 Corresponding author: Eun Ji Kim, Center for Efficacy Assessment and Development of Functional Foods and Drugs, Hallym University, Chuncheon, Gangwon 2-72, Korea E-mail: n-myej4@hallym.ac.kr, Phone: +82-33-248-316 론 고지혈증치료에대한많은연구가진행되었고그결과많은치료제가개발되어사용되고있으나치료제의장기복용에의한약효감소및부작용이대두되고있다 (3,4). 따라서안전하게사용할수있으며예방효과가있는기능성물질개발의필요성이요구되고있다. 발효식품에사용되는유산균은오래전부터섭취되어온 GRAS(Generally Recognizied As Safe) 로안전하며, 산업적으로빈번하게이용되고있다 (5). 일반적으로유산균의섭취는장내미생물들이음식물의소화, 흡수, 분해와배설등을돕는유익균의증가를유도하여소화작용을도와소화기계질환에개선효과를나타낸다 (6). 최근에는면역조절 (7), 항염 (8) 및항암 (9) 등다양한유산균의효능이알려지고있다. 또한많은연구자들은유산균이항비만 (1) 및혈중지질개선효과 (11-13) 가있음을보고하였다. 자연계에서가장분포가넓은유산균중의하나인 Lac-
Lactobacillus plantarum 혼합물의비만및지질대사개선효과 1485 tobacillus plantarum(l. plantarum) 은다양한생리활성을나타낸다. 최근의몇몇연구들은 L. plantarum 투여가식이에의해유도된비만 (14-16) 과고지혈증 (5,17,18) 을효과적으로억제함을보여주고있다. Bosch 등 (19) 은 in vitro 실험을통해 L. plantarum CECT 7527, 7528과 7529가콜레스테롤을감소할수있음을제시하였고, 3 종류를혼합시 bile salt hydrolase 생성이더많아짐을보고하였다. Fuentes 등 (2) 은고콜레스테롤혈증을나타내는사람에게 L. plantarum CECT 7527, 7528과 7529가동일한비율로혼합된혼합물을 1.2 1 9 colony-forming units(cfu) 용량으로 12주투여한경우혈중콜레스테롤함량이높은사람들에게혈중총콜레스테롤함량감소효과를나타냄을보고하였다. Fuentes 등 (2) 의인체적용연구는 L. plantarum CECT 7527, 7528과 7529 혼합물의고지혈증개선에활용가능성을제시하나단일투여용량에대해연구되었고혈액내지질함량만이평가되었으므로이를고지혈증개선에적용하기위해서는그효과를뒷받침할수있는더많은연구가필요할것으로사료된다. 본연구에서는고지방식이투여로비만및고지혈증을유도한동물에서 L. plantarum CECT 7527, 7528과 7529가동일한비율로혼합된혼합물 (L. plantarum 혼합물 ) 이비만및고지혈증에미치는영향을조사하고자하였다. 재료및방법시료본연구에서사용한 L. plantarum 혼합물은 L. plantarum CECT 7527, 7528, 7529가동일한비율로혼합되어있는혼합물로 SACCO srl.(cadorago, Italy) 에서제공받아실험에사용하였다. 실험동물사육및시료투여특정병원체가없는 5주령, 수컷 Sprague-Dawley(SD) rat을 ( 주 ) 오리엔트바이오 (Seongnam, Korea) 에서구입하여사용하였다. 실험동물은온도 23±3 C, 상대습도 5± 1%, 환기회수 1~15회 / 시간, 조명시간 12시간 (8:~ 2:), 조도 15~3 Lux로설정된사육환경에서사육하였다. 1주간의적응기간동안실험동물은실험동물용고형사료 (Cargil Agri Purina, Inc., Seongnam, Korea) 와음수를자유섭취하도록하였다. 1주일간의적응과정을거친뒤체중감소없는건강한동물을선별하여난괴법에의거하여대조군, 저용량 (.6 1 9 CFU/day) 투여군, 중용량 (1.2 1 9 CFU/day) 투여군, 고용량 (2.4 1 9 CFU/day) 투여군으로분류하였고, 각실험군당 1마리의실험동물을사용하였다. 비만및고지혈증상을유도하기위해실험기간동안실험동물에게는고지방식이 [ 에너지비율 (kcal%); 단백질 : 탄수화물 : 지방 =2:2:6, Research Diets, Inc., New Brunswick, NJ, USA] 를공급하였고, 사료와음수는자유 로이섭취할수있게하였다. 고지방식이에의한고지혈증상을확인하기위해 5마리의건강한실험동물을실험군과같은조건에서대조식이 [ 에너지비율 (kcal%); 단백질 : 탄수화물 : 지방 =2:7:1, Research Diets, Inc.] 를공급하여사육하였고실험종료전에혈액을취해혈청지질함량을측정하여고지방식이에의한고지혈유도여부를확인하였다. L. plantarum 혼합물은멸균생리식염수에녹여일정한시간에 8주동안 1일 1회경구투여하였다. 실험기간동안실험동물의체중은주 1회일정한시간에측정하였고, 식이섭취량은 2일간격으로측정하였다. 본연구에서의모든동물실험은한림대학교동물실험윤리위원회의승인하에수행되었다 (Hallym 213-89). 채혈및장기무게측정실험동물을희생전 12시간동안절식시킨후 Avertin (Sigma-Aldrich Co., St. Louis, MO, USA) 을사용하여마취하고개복하여심장에서채혈하였다. 혈액은 serum separate tube(becton Dickinson, Franklin Lakes, NJ, USA) 에담아 3분간실온에서방치하고 3, rpm으로실온에서 2분간원심분리하여혈청을분리하였으며수집된혈청은 test tube에모아분석전까지 -7 C에보관하였다. 혈액채취후즉시간과부고환지방을적출하고차가운생리식염수에세척한후여과지로여분의물기를제거한후무게를측정하였다. 채취한간은액체질소로급속냉동시킨후 -7 C에보관하였다. 혈중지질및혈당분석혈액생화학분석기 (Konelab 2XT, Thermo Fisher Scientific, Waltham, MA, USA) 를이용하여혈청내의총콜레스테롤, LDL(low density lipoprotein)-콜레스테롤, HDL(high density lipoprotein)-콜레스테롤, 중성지방및혈당을측정하였다. 심혈관계질환의위험도판정에사용되는동맥경화지수 (atherogenic index, AI) 와심장질환지수 (cardiac risk factor, CRF) 는아래와같은식으로산출하였다 (21). AI= CRF= Total cholesterol-hdl-cholesterol HDL-cholesterol Total cholesterol HDL-cholesterol 혈청렙틴함량분석혈청중렙틴함량은 ELISA kit(r&d Systems, Minneapolis, MN, USA) 을사용하여제조회사에서제시한방법에따라측정하였다. 간조직내지질분석간조직내의지질은 Folch 등 (22) 의방법으로추출하였다. 즉 1 g의간조직을 saline 3 ml에넣고균질화시킨후
1486 김대환 최미란 홍지은 이재용 이순임 정수환 김은지 CM solution(chloroform : methanol=2:1) 을 9 ml 넣고균질화하였다. 균질액은 3, rpm에서 1분간원심분리하고아래층을취하여증발시켜지질을얻었으며정밀저울을사용하여총지질량을측정하였다. 간조직내의중성지방과총콜레스테롤함량은추출하여얻은총지질에 iso-prophanol을넣어녹인후효소법을이용한측정 kit(asan Parmaceutical, Seoul, Korea) 을사용하여제조회사에서제시한방법에따라측정하였다. 통계처리본연구의모든분석수치는 mean±sem으로나타내었다. 수집된결과는 SAS(Statistical Analysis System) Window v. 9.1 프로그램 (SAS Institute, Cary, NC, USA) 을이용하여통계분석하였으며, 각실험군의평균치간에 α=.5 수준에서 analysis of variance와 Duncan's multiple range test에의해분석하였다. 며, L. plantarum 혼합물고용량투여군의일일체중증가량은 L. plantarum 혼합물을투여하지않은대조군에비해 13.9% 감소하였다 (Table 1). 이는 L. plantarum 혼합물이항비만효과가있음을나타낸다. L. plantarum 혼합물저용량투여군과중용량투여군의식이섭취량은감소하는경향을나타냈으나대조군과유의적인차이가없었고, L. plantarum 혼합물고용량투여군의식이섭취량은대조군에비해유의적으로감소하였다. 식이효율은 L. plantarum 혼합물투여에의해변화하지않았다 (Table 1). 몇몇연구는활생균 (probiotic) 투여가식욕및포만감을조절하는장내호르몬에영향을미쳐에너지섭취를감소하고체중증가를감소한다고보고하였다 (24). 본연구를통해 L. plantarum 혼합물의식이섭취량감소기전을알수없으나 L. plantarum 혼합물투여에의한식이섭취량감소로에너지섭취가감소하여 L. plantarum 혼합물투여에의한체중감소에영향을미쳤음을알수있다. 결과및고찰체중변화및식이효율에미치는영향 L. plantarum은종에따라다양한특성을나타낸다. L. plantarum No.14(14), L. plantarum PL62(15) 및 L. plantarum LG42(16) 는고지방식이에의한체중증가를감소하여항비만효과가있음이보고되고있다. 반면 L. plantarum Lp91과 Lp21(17), L. plantarum LS/7과 Biocenol LP96 (18) 및 L. plantarum OLL2712(23) 는체중감소효과를나타내지않았다. L. plantarum 혼합물의항비만효과를조사하기위해고지방식이를급여하여비만을유도한흰쥐의체중에미치는영향을조사하였다. 흰쥐에고지방식이를급여하며다양한용량 ( CFU/day,.6 1 9 CFU/day, 1.2 1 9 CFU/day, 2.4 1 9 CFU/day) 의 L. plantarum 혼합물을 8주간경구투여하였고, 체중및식이섭취량을조사하여 Table 1에나타내었다. 흰쥐의초기체중은실험군간유의적인차이를나타내지않았다. 초기체중이 28.8±2.6 g이었던흰쥐에게고지방식이를급여하여 8주사육한경우최종체중이 61.±9. g이되었고, 일일체중증가량이 7.2±.2 g이었다. 고용량으로 L. plantarum 혼합물을투여한경우최종체중및일일체중증가량이유의적으로감소하였으 장기무게에미치는영향고지방식이급여는흰쥐의간과부고환지방의무게를현저히증가시킨다 (25). 장기간의고지방식이섭취는혈액으로지방의유입을증가시켜간에지방의축척을유도하며 (26), 고지방식이는당대사에불균형을초래하고이로인해포도당의유입이증가하여간이비대하게된다 (27). 부고환지방은체내잉여에너지를지방으로저장된백색지방이며 (28), 흰쥐에서내장비만의주요한지표로혈중지질함량등대사적변화를초래한다 (29). 고지방식이급여에의해증가한간과부고환지방무게에 L. plantarum 혼합물이미치는영향을조사하기위해간과부고환지방을적출하여무게를측정하였다. 간의무게는 L. plantarum 혼합물투여에의해유의적으로감소하였고, 고용량의 L. plantarum 혼합물투여에의해부고환지방의무게는현저히감소하였다. L. plantarum 혼합물고용량투여군의간과부고환지방의무게는대조군에비해각각 21.5%, 19.6% 감소하였다 (Table 2). L. plantarum 혼합물에의한간과부고환지방무게의감소는 L. plantarum 혼합물이항비만효과가있음을나타낸다. Table 1. Effect of a mixture of Lactobacillus plantarum CECT 7527, 7528, and 7529 (M-LP) on body weight gain, food intake, food efficiency ratio (FER) in rats fed a high-fat diet Initial body weight (g) Final body weight (g) Body weight gain (g/day) Food intake (g/day) FER 1) 28.8±2.6 61.±9. a 7.2±.2 a 2.±.3 a.36±.1 M-LP-Low.6 1 9 M-LP-Medium 1.2 1 9 M-LP-High 2.4 1 9 27.5±2.8 21.6±2.9 27.7±2.9 58.7±16.4 ab 586.8±8.9 ab 555.4±13.7 b 6.7±.3 ab 6.7±.3 ab 6.2±.3 b 19.9±.4 a 19.6±.5 a 18.2±.4 b.34±.2.35±.1.35±.2 Values are expressed as the means±sem (n=1). Means without a common letter differ significantly at P<.5. 1) FER (food efficiency ratio)=body weight gain (g)/ food intake (g).
Lactobacillus plantarum 혼합물의비만및지질대사개선효과 1487 Table 2. Effect of a mixture of Lactobacillus plantarum CECT 7527, 7528, and 7529 (M-LP) on organs weight in rats fed a highfat diet Liver weight (g) Epididymal fat weight (g) M-LP-Low M-LP-Medium M-LP-High.6 1 9 1.2 1 9 2.4 1 9 16.55±.69 a 14.6±.55 b 14.1±.63 b 13.±.46 b 16.98±1.15 a 14.9±.61 ab 14.71±.55 ab 13.65±.75 b Values are expressed as the means±sem (n=1). Means without a common letter differ significantly at P<.5. 혈청지질함량및동맥경화지수와심혈관위험지수에미치는영향비만에서는지방대사와당대사의이상으로인하여이상지혈증이흔히동반된다. Lee 등 (3) 과 Jang과 Choi(31) 는고지방식이에의해비만이유도된흰쥐에서혈중중성지방과콜레스테롤은증가하고 HDL-콜레스테롤이감소하였다고보고하였다. 고지방식이에의한고지혈유도여부를판단하기위해대조식이를섭취한동물의혈청내의중성지방과총콜레스테롤함량을측정하였고혈청내의중성지방과총콜레스테롤함량은각각 68.6±13.85 mg/dl와 74.93± 5.44 mg/dl였다 (data not shown). 고지방식이를섭취한동물의혈청내의중성지방과총콜레스테롤함량은 71.64± 4.92 mg/dl와 83.99±3.13 mg/dl였다 (Table 3). 이는고지방식이섭취에의해고콜레스테롤혈증이유도됨을나타낸다. Table 3에나타난바와같이 L. plantarum 혼합물은혈청중성지방함량과 HDL-콜레스테롤함량에는영향을미치지않았다. 또한혈당의함량도 L. plantarum 혼합물투여에의해변하지않았다. 반면중용량과고용량의 L. plantarum 혼합물투여에의해혈청총콜레스테롤함량은유의적으로감소하였고, LDL-콜레스테롤함량은 L. plantarum 혼합물투여에의해현저히감소하였다. 고용량의 L. plantarum 혼합물투여군의혈청총콜레스테롤과 LDL-콜레스테롤함량은각각대조군에비해 26.%, 26.7% 감소하였다 (Table 3). 항비만효과를나타냈던 L. plantarum PL62 (15) 와 L. plantarum LG42(16) 는혈중중성지방함량을유의적으로낮추었으나혈청콜레스테롤함량에는영향을미치지않았다. L. plantarum LS/7과 Biocenol LP96(18) 은혈청총콜레스테롤함량은감소하였으나 LDL-콜레스테롤의함량에는영향을미치지않았다. Kumar 등 (17) 은 L. plantarum Lp91과 Lp21이혈청총콜레스테롤및 LDL-콜레스테롤함량을감소하였다고보고하였고, 고콜레스테롤혈증개선효과가있는활생균 (probiotic) 임을제시하였다. 본연구결과는 L. plantarum 혼합물이혈청총콜레스테롤과 LDL-콜레스테롤함량을감소하여고콜레스테롤혈증개선효과를나타낼수있음을제시한다. 위에서얻은혈중지질함량결과를계산하여동맥경화지수와심혈관위험지수를구해 Table 4에나타내었다. 동맥경화지수는체내 HDL-콜레스테롤에대한중성지질의농도를대표하는값으로임상에서 3. 이상의값을나타낼때동맥경화에대한위험신호로서사용하고있다 (32). HDL-콜레스테롤에대한총콜레스테롤의농도를나타내는값인심혈관위험지수는동맥경화지수와같게심혈관계질환에대한위험신호로사용되고있으며, 임상에서 7. 이상인경우위험상태로판단된다 (33). L. plantarum 혼합물을투여한경우동맥경화지수와심혈관위험지수가유의적으로감소하였다. 특히고용량의 L. plantarum 혼합물투여군의동맥경 Table 3. Effect of a mixture of Lactobacillus plantarum CECT 7527, 7528, and 7529 (M-LP) on serum lipid profiles and glucose in rats fed a high-fat diet Triglyceride (mg/dl) Total cholesterol (mg/dl) HDL-cholesterol (mg/dl) LDL-cholesterol (mg/dl) Glucose (mg/dl) 71.64±4.92 83.99±3.13 a 29.61±1.74 8.27±.67 a 167.5±8.34 M-LP-Low M-LP-Medium M-LP-High.6 1 9 1.2 1 9 2.4 1 9 67.18±6.29 75.22±3.57 ab 3.17±1.37 6.48±.36 b 164.4±9.19 65.73±5.4 73.91±2.53 b 3.53±1.47 6.32±.25 b 166.95±5.26 Values are expressed as the means±sem (n=1). Means without a common letter differ significantly at P<.5. 71.44±3.3 62.41±3. c 31.23±1.27 6.6±.27 b 173.67±6.23 Table 4. Effect of a mixture of Lactobacillus plantarum CECT 7527, 7528, and 7529 (M-LP) on atherogenic index (AI) and cardiac risk factor (CRF) in rats fed a high-fat diet AI 1) CRF 2) M-LP-Low.6 1 9 M-LP-Medium 1.2 1 9 M-LP-High 2.4 9 1.91±.19 a 1.5±.4 b 1.48±.15 b 1.2±.12 c 2.91±.19 a 2.5±.4 b 2.48±.15 b 2.2±.12 c Values are expressed as the means±sem (n=1). Means without a common letter differ significantly at P<.5. 1) AI (atherogenic index)=(total cholesterol-hdl-cholesterol)/ HDL-cholesterol. 2) CRE (cardiac risk factor)=total cholesterol/ HDL-cholesterol.
1488 김대환 최미란 홍지은 이재용 이순임 정수환 김은지 Table 5. Effect of a mixture of Lactobacillus plantarum CECT 7527, 7528, and 7529 (M-LP) on hepatic lipid profiles in rats fed a high-fat diet M-LP-Low M-LP-Medium M-LP-High.6 1 9 1.2 9 2.4 1 9 Total lipid (mg/g liver) Triglyceride (mg/g liver) Total cholesterol (mg/g liver) 142.23±13.55 a 5.22±.24 a.95±.1 a 132.64±8.14 ab 4.73±.25 ab.91±.3 ab 111.33±8.29 b 4.4±.29 b.9±.2 ab 19.26±8.2 b 4.39±.26 b.87±.2 b Values are expressed as the means±sem (n=1). Means without a common letter differ significantly at P<.5. Leptin (ng/ml). 7 6 5 4 3 2 1 a a Vehicle Low Medium High M-LP Fig. 1. Effect of a mixture of Lactobacillus plantarum CECT 7527, 7528, and 7529 (M-LP) on serum leptin levels in rats fed a high-fat diet. The mice were treated with a mixture of Lactobacillus plantarum CECT 7527, 7528, and 7529 (M-LP) as described in Materials and Methods. Blood samples were collected from the mice at the time of sacrifice, and the sera were prepared. Serum levels of leptin were measured with a leptin ELISA kit. Each bar represents as the mean±sem (n=1). Means without a common letter differ significantly at P<.5. 화지수와심혈관위험지수는대조군에비해각각 46.6%, 3.6% 감소하였다 (Table 4). 이는 L. plantarum 혼합물이고지혈증, 고혈압및심혈관질환의위험감소에도움을줄수있음을제시한다. 고콜레스테롤혈증을나타내는사람들에게실시한인체적용연구에서는본연구에서사용한동일한 L. plantarum 혼합물을 1.2 1 9 CFU 용량으로 12주동안섭취시혈중콜레스테롤함량이감소하였다 (2). 본연구에서 L. plantarum 혼합물을 1.2 1 9 CFU 용량으로 8주투여시인체적용연구의결과와같이혈중콜레스테롤함량이감소하였다. 또한투여용량을 2.4 1 9 CFU로증가한경우혈중콜레스테롤함량감소뿐만아니라체중감소및간과지방의무게감소효과를나타내었다 (Table 1, 2). 본동물실험결과는인체에서투여용량을증가할시고콜레스테롤혈증개선효과와더불어항비만효과를나타낼수있음을제시한다. 간조직지질함량에미치는영향간은중성지방과콜레스테롤의주요생합성장소이고대사가이루어지는장소이다. 간에서합성된중성지방등의지질성분이정상적으로대사되지않는경우축척되어지방간이유발된다 (34). 특히고지방식이섭취시혈액내유리지방산수준이증가하여간으로의유리지방산의유입이증가하게되고간에서의중성지방합성이증가되어간에중성지방이축적되며이는비만과대사증후군을초래한다 (26). 또한고지방식이섭취시혈중중성지방의농도가상승하게되어간에서중성지방의운반을담당하는 very low-density lipoprotein(vldl) 의생성이증가하고 VLDL로부터전환된 LDL이증가하게된다. 간에서증가된 LDL을제거하는과정에서간조직내의총콜레스테롤이증가한다 (35). L. plantarum 혼합물투여가간조직지방함량에미치는영향을조사하여 Table 5에나타내었다. 간조직내의총지질함량은 L. plantarum 혼합물투여에의해현저히감소하였다. L. plantarum 혼합물투여한경우간조직내의중성지방함량과총콜레스테롤함량이감소하였다. 간조직내의중성지방함량은고용량의 L. plantarum 혼합물투여에의해 15.9% 감소하였고, 고용량의 L. plantarum 혼합물투여에의해간조직내의총콜레스테롤함량은 8.4% 감소하였다. Salaj 등 (18) 은 L. plantarum LS/7과 Biocenol LP96 이혈청총콜레스테롤함량은감소하였으나간조직내의지질함량에는영향을미치지않음을보고하였다. L. plantarum LG42(16) 는혈중중성지방함량과간조직내의중성지방을감소하였다. 이결과들은 L. plantarum 혼합물이다른 L. plantarum에비해더효과적으로지질대사를개선할수있음을보여준다. 혈청렙틴함량에미치는영향지방조직에서분비되는호르몬인렙틴은에너지과잉섭취할경우식욕억제를위해생성이증가한다. 혈청렙틴의양은체중및체지방과양의상관관계가있고 (36), 비만인경우고렙틴혈증이특징적으로나타나고이로인해렙틴저항성 (leptin resistance) 이유발된다 (37). Fig. 1에나타난바와같이고지방식이만을 8주동안섭취한흰쥐의혈청렙틴함량은 5.4±.3 ng/ml로고렙틴혈증을나타냈다. 저용량과중용량의 L. plantarum 혼합물투여에의해혈청렙틴함량은유의적인차이를나타내지않았으나고용량 L. plantarum 혼합물투여군의혈청렙틴함량은현저히감소하였고, 이는 L. plantarum 혼합물이고렙틴혈증개선효과가있음을보여준다. 요 본연구에서는고지방식이투여로비만및고지혈증을유도 약 a b
Lactobacillus plantarum 혼합물의비만및지질대사개선효과 1489 한동물에서 L. plantarum CECT 7527, 7528과 7529 혼합물이비만및고지혈증에미치는영향을조사하고자하였다. 흰쥐에 8주동안고지방식이를급여하면서 L. plantarum 혼합물을.6~2.4 1 9 CFU/day를경구투여하였고동물을희생하여혈청및간조직내의지질함량을조사하였다. L. plantarum 혼합물투여에의해체중증가량, 간과부고환지방무게가현저히감소하였다. 또한비만과관련있는호르몬인혈청렙틴의함량이 L. plantarum 혼합물투여에의해감소하였다. L. plantarum 혼합물투여가혈청중성지방과 HDL-콜레스테롤함량및혈당에는영향을미치지않았으나혈청총콜레스테롤함량및 LDL-콜레스테롤함량을현저히감소하였다. 이와더불어 L. plantarum 혼합물투여가동맥경화지수와심혈관위험지수를유의적으로감소하였다. 간조직내의총지질함량, 중성지방함량및총콜레스테롤함량은 L. plantarum 혼합물투여에의해유의적으로감소하였다. 이상의결과는 L. plantarum CECT 7527, 7528 과 7529가혼합된 L. plantarum 혼합물이체지방감소및고지혈증개선효과를나타냄을보여준다. 향후더많은연구가필요하나본연구는 L. plantarum 혼합물을비만및고지혈증개선제로개발할수있는가능성을제시한다. 감사의글 본연구는 213년도산업통상자원부지역혁신센터사업 ( 한림대학교식의약품의효능평가및기능성소재개발센터 ) 과한올바이오파마주식회사의지원에의해이루어진것으로이에감사드립니다. REFERENCES 1. Ministry of Health and Welfare. 213. Korea Health Statistics 212: Korea National Health and Nutrition Examination Survey. Seoul, Korea. p 44-47. 2. Lee JH. 1992. Treatment of obesity. Korean J Obes 1: 21-24. 3. Yum KS. 21. 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