CN111801413A - 鼠李糖乳杆菌lm1019菌株及包含其的用于预防及治疗肥胖或糖尿病的组合物 - Google Patents
鼠李糖乳杆菌lm1019菌株及包含其的用于预防及治疗肥胖或糖尿病的组合物 Download PDFInfo
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Abstract
本发明涉及鼠李糖乳杆菌LM1019菌株(Lactobacillus rhamnosus LM1019,保藏编号KCCM12308P)及包含其的用于预防及治疗肥胖或糖尿病的组合物。具体地,本发明的鼠李糖乳杆菌LM1019菌株具有如下的效果,即,通过减少脂肪细胞、中性脂肪、皮下脂肪及胆固醇来预防及治疗肥胖,同时,通过减少血糖浓度及胰岛素浓度来抑制胰岛素抗性,从而预防及治疗糖尿病。
Description
技术领域
本发明涉及新的鼠李糖乳杆菌LM1019(Lactobacillus rhamnosus LM1019)菌株及包含其的用于预防及治疗肥胖或糖尿病的组合物。具体地,本发明的鼠李糖乳杆菌LM1019菌株具有如下的效果,即,通过减少脂肪细胞、中性脂肪、皮下脂肪及胆固醇来预防及治疗肥胖,同时,通过减少血糖浓度及胰岛素浓度来抑制胰岛素抗性,从而预防及治疗糖尿病。并且,鼠李糖乳杆菌LM1019还参与作为脂解酶的脂肪酶、作为食欲调节激素的瘦素、肥胖相关基因肉毒碱棕榈酰转移酶(Carnitine palmitoyltransferase,CPT)的表达。
背景技术
最近,由于收入水平的提高及产业的发达,饮食生活、饮食习惯等生活习惯迅速西化,使得慢性疾病或成人病患者急剧增加,其原因之一为肥胖。
肥胖为摄入能量与消耗能量不均衡引起的能量代谢异常,最终定义为在脂肪细胞过度堆积中性脂肪的状态。
肥胖为一种世界性的慢性疾病,没有有效地治疗方法,呈持续增长趋势的严重的疾病。与其他疾病不同地,肥胖不仅具有外形上的问题,还具有体重增加的同时伴随代谢疾病、高血压、糖尿病、高脂血症、动脉硬化症、缺血性心脏疾病、脂肪肝、胆石症等相关疾病。
肥胖本身为一种严重的疾病,但还引起美容问题,因此,在世界各国积极研发各种肥胖治疗剂,且已研发出各种肥胖治疗剂。目前为止所研发的肥胖治疗剂大致分为食欲抑制剂类的肥胖治疗剂和脂解抑制剂类的肥胖治疗剂。
食欲抑制剂类的肥胖治疗剂具有优秀的减重效果,但是,这些食欲抑制剂类的肥胖治疗剂具有作用于中枢神经系统来降低食欲,从而减少食物摄入量的作用机制,没有长期效果,且当长期使用时,存在引发严重的副作用的要害问题。
作为初期食欲抑制剂类的肥胖治疗剂,产品化的有芬氟拉明(fenfluramine)、西布曲明(sibutramine)及利莫那班(rimonabant),但具有心脏疾病、血压上升、心脏麻痹增加、抑郁症及自杀等严重的精神疾病副作用问题,因此停止被销售。
作为脂解抑制剂类的肥胖治疗剂,奥利司他(orlistat)(商品名:罗氏鲜(Xenical)与作为用于分解中性脂肪的胰脏的脂解酶的胰脂肪酶(pancreatic lipase)不可逆耦合来使其失活,减少中性脂肪及胆固醇的吸收的同时促进排泄,从而起到抗肥胖作用。
因此,若服用奥利司他,则抑制脂解,且,通过食物摄入的脂肪不被体内吸收,而是排出体外,来减少人体吸收的脂肪量,从而减少体重。但据报告,即使具有如上所述的功效,奥利司他也具有腹痛、腹泻、脂溶性维生素吸收抑制等副作用,当长期服用时,具有严重的肝损伤,因此,需要重新审查奥利司他的安全性。
目前,市面上的大部分肥胖治疗剂均具有严重的副作用,因此,对于无副作用且能有效治疗肥胖的肥胖治疗剂的社会需求很高。因此,世界各国正为了研发无副作用且能有效治疗肥胖的肥胖治疗剂而进行各种研究,但目前为止,并未研发并销售这种肥胖治疗剂。
与此相反地,乳酸菌以不被体内吸收且停留在肠内空间来与人体共生的状态存在,因此,正研究将具有优秀的安全性的乳酸菌用作治疗剂的方案。
乳酸菌在人体的消化系统共生,同时,分解纤维及复合蛋白来使其成为重要的营养成分。如上所述,将在包括人在内的动物的肠胃内改善宿主的肠内微生物环境来有益于宿主的健康的活微生物统称为益生菌(probiotics)。
益生菌被认为具有能调节代谢及免疫功能的能力,代表性的益生菌包括乳杆菌属(Lactobacillus sp.)、乳球菌属(Lactococcus sp.)菌株等。其中,乳杆菌属菌株为在人体肠道内栖息的正常微生物群落的主要成员,在维持健康的消化器官和阴道环境方面发挥重要作用。
对此,在日本专利申请第2016520305号(2016年07月14日公开)公开了具有抗肥胖活性的坂乳杆菌属的WIKIM31菌株,在美国专利申请第2015/0283186号(2015年10月08日公开)公开了有效管理肥胖的鼠李糖乳杆菌CNCM I-3690菌株,在韩国授权专利第101611837号(2016年04月06日公开)公开了用于预防或治疗肥胖及肥胖引起的代谢疾病的鼠李糖乳杆菌CBT LR5菌株,但未公开这些菌株在小肠细胞或消化道内的脂解抑制效果及食欲调节效果。
因此,本发明人发现益生菌中的鼠李糖乳杆菌LM1019抑制参与3T3-L1脂肪细胞分化诱导的基因的mRNA及蛋白质的表达,最终抑制3T3-L1脂肪细胞分化及脂肪堆积,从而完成本发明。
发明内容
为发现具有优秀的抗肥胖效果的益生菌而不断努力的结果,本发明人确认鼠李糖乳杆菌LM1019菌株具有优秀的抗肥胖效果,从而完成本发明。
令人惊讶的是,LM1019菌株不仅同时具有抑制脂肪细胞分化、抑制脂肪堆积及食欲调节效果,还具有减少胰岛素抗性的显著效果。
本发明人发现,鼠李糖乳杆菌LM1019菌株不仅具有抑制脂肪细胞分化、抑制脂肪堆积的效果,还具有减少食欲及饮食效率的效果,即使在正常饮食或高营养饮食条件下,也可有效地预防及治疗肥胖及超重。
并且,本发明人确认,鼠李糖乳杆菌LM1019菌株通过减少血糖浓度及胰岛素浓度来减少能与肥胖一同发生的胰岛素抗性。
本发明确认,鼠李糖乳杆菌LM1019菌株通过抑制脂肪前体细胞分化为脂肪细胞及细胞内脂肪堆积以及减少体重、腹部脂肪及血中胆固醇等各种作用机制、酶、激素及基因表达有效地治疗及预防包括肥胖在内的高脂血症、代谢疾病及糖尿病。
并且,本发明提供鼠李糖乳杆菌LM1019菌株及包含其的用于预防及治疗肥胖、超重、高脂血症、代谢疾病及糖尿病的组合物。
本发明涉及在韩国微生物保藏中心(Korean Culture Center ofMicroorganisms;KCCM)托管的保藏编号为KCCM12308P的鼠李糖乳杆菌LM1019。
本发明的鼠李糖乳杆菌LM1019在2017年08月11日在韩国微生物保藏中心以KFCC11725P国内托管(domestic deposit),并在2018年09月05日在韩国微生物保藏中心以KCCM12308P国际托管(international deposit)相同的菌株。
本发明涉及具有同时预防或治疗肥胖及糖尿病的功效的鼠李糖乳杆菌LM1019菌株(KCCM12308P)。
本发明涉及如下的用于预防或治疗肥胖或糖尿病的药学组合物,即,包含鼠李糖乳杆菌LM1019菌株,所述鼠李糖乳杆菌LM1019菌株在小肠细胞或消化道同时具有脂解抑制效果及食欲调节效果。
此时,所述脂解抑制可通过抑制脂肪酶的活性来实现,所述食欲调节可通过减少瘦素激素的分泌来实现。
并且,在所述药学组合物中,鼠李糖乳杆菌LM1019菌株可减少胰岛素抗性。
本发明涉及肥胖或糖尿病的治疗方法,其包括向需要治疗肥胖或糖尿病的对象给鼠李糖乳杆菌LM1019菌株有效量。
此时,所述鼠李糖乳杆菌LM1019菌株可在给药对象的小肠细胞或消化道同时具有脂解抑制效果及食欲调节效果。
并且,所述脂解抑制可通过抑制脂肪酶的活性来实现,所述食欲调节可通过减少瘦素激素的分泌来实现。
并且,所述鼠李糖乳杆菌LM1019菌株可减少给药对象的胰岛素抗性。
本发明涉及如下的用于预防或改善肥胖或糖尿病的食品组合物,即,包含鼠李糖乳杆菌LM1019菌株(KCCM12308P),所述鼠李糖乳杆菌LM1019菌株可在小肠细胞或消化道同时具有脂解抑制效果及食欲调节效果,此时,所述食品组合物可以为健康功能食品、乳制品、发酵产品或食品添加剂。
本发明涉及如下的用于预防或改善肥胖或糖尿病的动物饲料组合物,即,包含鼠李糖乳杆菌LM1019菌株(KCCM12308P),所述鼠李糖乳杆菌LM1019菌株可在小肠细胞或消化道同时具有脂解抑制效果及食欲调节效果。
发明效果
本发明的鼠李糖乳杆菌LM1019菌株抑制脂肪细胞分化及细胞内脂肪堆积,从而具有优秀的抗肥胖效果。
并且,本发明的鼠李糖乳杆菌LM1019菌株减少体脂量、总胆固醇、血浆中性脂肪及肝组织中性脂肪,从而具有预防或治疗肥胖或肥胖引起的代谢疾病及高脂血症的效果。
并且,本发明的鼠李糖乳杆菌LM1019菌株通过减少血糖及胰岛素浓度来改善胰岛素抗性,从而具有预防或治疗肥胖及肥胖引起的糖尿病的效果。
并且,本发明的鼠李糖乳杆菌LM1019菌株抑制作为脂解酶的脂肪酶的活性来抑制体内脂肪吸收并促进排出,通过减少作为食欲调节激素的瘦素的合成来抑制食欲,增加参与将脂肪氧化来转换为能量的酶的肉毒碱棕榈酰转移酶的基因表达,从而具有通过调节各种酶及激素来预防或治疗肥胖及肥胖引起的疾病的效果。
附图说明
图1示出利用油红O(Oil-red-O)对在3T3-L1前脂肪细胞分别处理1%的LM1019培养提取物处理组、10%的LM1019培养提取物处理组以及作为对照组的磷酸缓冲盐溶液(PBS)而分化的脂肪细胞染色后,所呈现的脂肪细胞内脂肪球的数(箭头)。
图2示出第一组至第三组的随着时间的体重增加率。
图3示出各个组的皮下脂肪、附睾脂肪及棕色脂肪组织的重量。
图4为测定在附睾脂肪利用苏木精-伊红染色法(H&E stain)对各个组染色的脂肪组织的数量及脂肪细胞大小的图。
图5示出各个组的肝脏、脾脏及肾脏的重量。
图6示出利用苏木精-伊红染色法对各个组的肝脏染色并以20倍率(A、B、C)及40倍率(D、E、F)观察有无大脂肪泡(macro fat vacuole)的结果。
图7示出测定各个组的肝脏或附睾脂肪中的肉毒碱棕榈酰转移酶Ⅱ基因表达的结果。
具体实施方式
肥胖(obesity)为食物摄入与能源消耗之间的不均衡引起的代谢障碍,为体内堆积过多脂肪的状态。并且,肥胖与胰岛素抗性、葡萄糖耐量、高脂血症、代谢疾病等密切相关。因此,肥胖会诱发高脂血症、代谢疾病及糖尿病等。
高脂血症为过多的脂肪成分物质存在于血液内并堆积在血管壁来诱发炎症,从而诱发心血管疾病的状态,由于遗传上的原因,血液内的特定脂质增加而诱发高脂血症的情况较多,还可通过如肥胖及糖尿病等的其他原因诱发高脂血症。
代谢疾病包括多个代谢疾病,其中,多数促进动脉硬化症的发病,并增加心血管疾病的发病风险。虽未完全发现代谢疾病的作用机制,患有代谢疾病的大部分患者的胰岛素浓度增加且具有胰岛素抗性。
糖尿病为葡萄糖代谢发生异常而诱发的代谢疾病的一种。其特征为血中葡萄糖的浓度变高的高血糖,由此,具有各种症状及征兆,并通过小便排出葡萄糖。据悉,糖尿病患者的30~70%左右为遗传,最近,在韩国急速增加的为2型糖尿病,这与生活方式的西化及肥胖患者的增加有密切关系。
本发明涉及鼠李糖乳杆菌LM1019菌株在小肠细胞或消化道同时具有脂解抑制效果及食欲调节效果的用于预防或治疗肥胖或肥胖引起的疾病的组合物。
所述“脂解抑制”可通过菌株抑制脂肪酶的活性并在小肠细胞或消化道减少脂肪分解来抑制脂肪在体内吸收来实现。
脂肪酶为在胰脏生成并向十二指肠分泌的中性脂肪分解酶,帮助分解及吸收脂肪。因此,若抑制所述酶的活性,则分解中性脂肪的同时抑制小肠细胞及消化道吸收脂肪,因此,中性脂肪不被吸收,直接通过大便排出,最终可减少在体内堆积的脂肪。还具有自身分泌脂肪酶的菌。
所述“食欲调节”可通过使菌株增加瘦素激素的分泌来抑制或减少食欲来实现。
并且,本发明涉及鼠李糖乳杆菌LM1019菌株减少胰岛素抗性的用于预防或治疗肥胖或肥胖引起的疾病的组合物。
胰岛素抗性意味着降低血糖的胰岛素的功能降低而使细胞无法有效地燃烧葡萄糖,肥胖直接影响胰岛素抗性。胰岛素抗性增加后,在肝脏无法调节葡萄糖的生成,在肌肉无法利用葡萄糖,在脂肪中血糖转换为脂肪而无法堆积。在胰岛素抗性高的情况下,人体生成较多的胰岛素,由此,可诱发高血压或高脂血症、糖尿病等。
胰岛素抗性通过遗传上的理由及各种环境因素而产生,环境因素有运动不足、肥胖及摄入过多的热量等。
本发明的组合物可用于医药品、健康功能食品、乳制品、发酵产品、食品添加剂或动物用饲料等。
以下,通过实施例更加详细地说明本发明。这些实施例用于更加具体地说明本发明,本发明的范围并不局限于这些实施例。
实施例1
3T3-L1前脂肪细胞中的脂肪细胞分化抑制及脂肪堆积抑制作用
为了确认以保藏编号KCCM12308P托管在韩国微生物保藏中心的鼠李糖乳杆菌LM1019菌株在前脂肪细胞中的脂肪细胞分化抑制作用及细胞内脂肪堆积抑制作用,而进行如下的实验。
首先,利用油红O对在3T3-L1前脂肪细胞分别处理1%的LM1019培养提取物、10%的LM1019培养提取物以及作为对照组的磷酸缓冲盐溶液来完成经分化的脂肪细胞染色,1小时后通过显微镜观察被染色的细胞。
如图1所示,与添加磷酸缓冲盐溶液来代替LM1019培养提取物的对照组比较的结果,确认在利用LM1019培养提取物处理的处理组的脂肪细胞内脂肪球的数量(箭头)显著减少。相同的实验重复执行3次。
尤其,在10%的LM1019处理组的情况下,相比于1%的LM1019处理组,脂肪细胞及脂肪球的数量显著减少,脂肪细胞的分化根据浓度而明显不同。
因此,LM1019培养提取物具有抑制脂肪细胞的分化及细胞内脂肪堆积的效果,提取物的含量越高,所呈现的效果越优秀。
实施例2
3T3-L1脂肪细胞内中性脂肪分解促进及堆积抑制作用
为了确认分化为脂肪细胞的过程中所堆积的细胞内的中性脂肪(TG,甘油三酯)的量,分别添加1%及10%的LM1019菌株的提取物来培养,作为对照组,使用磷酸缓冲盐溶液代替菌株的提取物来培养。获取并使用分化第9日的脂肪细胞。
利用磷酸缓冲盐溶液清洗3次所获取的细胞并破碎菌体后,在4℃的温度条件下以15000rpm离心分离来将上层液用作试样。添加10μL的所述试样和150μL的酶试剂(enzymereagent),在常温条件下反应15分钟来测定530nm条件下的吸光度。
在下述表1示出测定脂肪细胞内的中性脂肪的结果。
表1
如所述表1所示,相对于对照组,1%的LM1019处理组及10%的LM1019处理组的中性脂肪减少量分别为14.1%及63.4%。
因此,可知,LM1019培养提取物促进脂肪细胞内的中性脂肪的分解并抑制堆积。
实施例3
脂肪分解酶(脂肪酶)活性测定
为了确认LM1019菌株的脂肪分解酶(脂肪酶)活性,进行如下的实验。
通过制备脂肪酶产生(lipase production)培养基,将LM1019绕成(streaking)圈(loop),并在37℃的温度条件下培养一晚。在生成脂肪酶的情况下,分解培养基内的橄榄油(olive oil)来生成单甘油酯(monoglyceride)。
单甘油酯通过与培养基内的罗丹明B(Rhodamin B)结合来在350nm的紫外线(UV)中发光,与使用大肠杆菌(E.coli)的对照组进行比较实验,对照组与LM1019菌株组均未发光。
对照组的单甘油酯的浓度为0.75nmol/well,LM1019菌株组的浓度为0.70nmol/well,相比于对照组,菌株组中的单甘油酯的浓度没有差异。
因此,LM1019菌株通过抑制脂肪分解酶(脂肪酶)的活性来抑制体内脂肪吸收并促进排出。并且,LM1019菌株不会自行分泌脂肪酶。
实施例4
实验动物中的抗肥胖效果实验
为了确认小鼠中的抗肥胖效果,将5周龄的C57BL6/J小鼠驯化1周后,分为3组来进行实验。
第一组为普通饮食(ND,3.1kcal/g)组,第二组为高脂饮食(HFD,5.2kcal/g)组,第三组为高脂饮食(HFD)并给药LM1019(109CFU/mouse)的组,每周5次口服给药。每周确认体重和给药的饮食量,并在第9周解剖并摘除主要脏器来测定重量。
体重增加率的减少
将0周的体重设为100%来测定随着时间的体重增加率并在图2示出。如图2所示,相比于第二组(HFD),第三组(HFD及LM1019给药组)在1周后呈现体重增加率差异。
在第7周,第三组的体重增加率为149.43%,第二组的体重增加率为159.44%,第三组的体重增加率比第二组的体重增加率减少10%。在第8周,第三组的体重增加率为149.33%,体重比第7周减少,与此相反地,第二组的体重增加率为171.46%,体重比第7周增加10%以上。尤其,在第8周,第三组的体重增加率比第二组的体重增加率减少20%以上。
如下述表2所示,第三组的8周期间的体重增加量为10.50,第二组的8周期间的体重增加量为14.84,具有约30%的差异。
最终,比较高脂饮食的第二组和高脂饮食的同时给药LM1019的第三组的结果,从1周后开始在体重增加率具有差异,并且,随着时间的推移,体重增加率的差异显著增加。
表2
第一组 | 第二组 | 第三组 | |
第7周的体重增加率(%) | 124.82 | 159.44 | 149.43 |
第8周的体重增加率(%) | 123.92 | 171.46 | 149.33 |
8周期间的体重增加量(g) | 4.86 | 14.84 | 10.50 |
食物利用率(food efficiency)的减少
在下述表3示出8周期间的体重增加量、每周饮食摄入量、热量摄入量、食物利用率。
表3
如所述表3所示,当比较每周饮食摄入量及热量摄入量时,第三组比第二组减少。并且,利用体重增加量和饮食摄入量计算食物利用率的结果,第二组为0.11,第三组为0.08,相比于饮食摄入量,体重增加量显著低。
皮下脂肪、附睾脂肪及棕色脂肪组织的减少
测定8周期间的皮下脂肪、附睾脂肪及棕色脂肪组织的量并在下述表4示出。
表4
第一组 | 第二组 | 第三组 | |
皮下脂肪(g) | 0.35 | 1.296 | 0.694 |
附睾脂肪(g) | 0.55 | 2.28 | 1.421 |
棕色脂肪组织(g) | 0.062 | 0.144 | 0.069 |
如所述表4及图3所示,第三组的体脂量比第二组的体脂量显著减少。
并且,通过苏木精-伊红染色法对附睾脂肪染色并在图4示出其结果。如图4所示,第二组的脂肪细胞的大小最大,第三组的脂肪细胞的大小比第二组的脂肪细胞的大小减少一半以上。
肝脏重量的减少
测定8周期间的肝脏、脾脏及肾脏的重量并在下述表5示出。
表5
第一组 | 第二组 | 第三组 | |
肝脏的重量(g) | 1.12 | 1.508 | 1.053 |
脾脏的重量(g) | 0.072 | 0.076 | 0.072 |
肾脏的重量(g) | 0.3 | 0.34 | 0.375 |
如所述表5所示,第三组的肝脏的重量比第二组的肝脏的重量显著减少。各个组的脾脏及肾脏的重量没有很大差异。
在肥胖的情况下,体内脂肪代谢发生异常而在肝内堆积脂质成分而增加肝脏的重量。如所述表5及图5所示,在给药LM1019菌株的组(第三组)中,肝脏的重量减少至正常水平,可知LM1019菌株参与肝中的脂质代谢具有抑制肝细胞的脂肪堆积的效果。
脂肪肝减少
通过苏木精-伊红染色法对肝脏染色并观察有无大脂肪泡(×20倍率及×40倍率),并在图6示出。
如图6所示,在第二组的肝脏组织的每一处观察到大脂肪泡(红色箭头),第一组及第三组的肝脏组织中未观察到大脂肪泡。
最终,可知LM1019菌株具有脂肪肝抑制效果。
血糖、中性脂肪及胆固醇数值减少
测定8周期间的血糖、中性脂肪及胆固醇数值并在下述表6示出。
表6
第一组 | 第二组 | 第三组 | |
葡萄糖(mg/dL) | 228.7 | 320.1 | 230.5 |
中性脂肪(mg/dL) | 147 | 165 | 103 |
胆固醇(mg/dL) | 136 | 218 | 173 |
在患有肥胖的情况下,产生胰岛素抗性,由此,血中胰岛素增加,由于代谢,使葡萄糖浓度暂时升高。如所述表6所示,第三组的血糖水平比第二组的葡萄糖水平低,可知,LM1019菌株对胰岛素抗性也具有积极效果。
并且,对于血中中性脂肪及胆固醇水平,也确认到第三组的数值比第二组的数值低。
胰岛素及瘦素的数值减少
测定8周期间的胰岛素及瘦素的数值并在下述表7示出。
表7
第一组 | 第二组 | 第三组 | |
胰岛素(ng/ml) | <0.1 | 1.00 | 0.46 |
瘦素(ng/ml) | 0.43 | 1.74 | 1.09 |
如上所述,在肥胖的情况下,胰岛素抗性增加而使胰岛素分泌增加,可确认,第三组的胰岛素浓度比第二组的胰岛素浓度显著减少。
因此,通过血糖浓度及胰岛素浓度的减少,可知,LM1019菌株具有显著的胰岛素抗性改善效果。
并且,瘦素为在脂肪细胞分泌的食欲调节激素,若在脂肪组织中堆积中性脂肪而使脂肪细胞的大小变大,则促进瘦素的合成来增加瘦素的浓度。
在与所述血中中性脂肪的浓度有关的实验中,相比于第二组,第三组的中性脂肪的浓度显著减少。即,第二组的中性脂肪及脂肪细胞减少,使得第三组的瘦素的浓度比第二组的瘦素的浓度显著减少。
肉毒碱棕榈酰转移酶基因表达增加
摘除8周期间给药LM1019菌株的小鼠的肝脏及附睾脂肪,并使用Trizol试剂(赛默飞世尔(Thermo scientific),美国(USA))提取RNA。之后,利用PrimeScriptTM 1st strandcDNA Synthesis kit(TAKARA,Japan)获取与RNA互补的DNA后,利用SYBR green(TAKARA,Japan)并通过实时聚合酶链式反应(PCR)确认作为与脂肪氧化相关的基因的肉毒碱棕榈酰转移酶Ⅱ表达。
肉毒碱棕榈酰转移酶基因为参与通过氧化脂肪来将脂肪转换为能量的酶,肉毒碱棕榈酰转移酶基因的数值越高,越促进脂肪的分解,并作为能量被消耗。
下述表8为用于实验的引物,甘油醛-3-磷酸脱氢酶(GAPDH)基因的mRNA表达为内部对照组(internal control)。
表8
如图7所示,在肝脏及附睾脂肪中确认肉毒碱棕榈酰转移酶Ⅱ基因的表达的结果,相比于第二组,作为实验组的第三组的表达量增加。对此使用甘油醛-3-磷酸脱氢酶来在表9示出2^-ddCt的平均数值。
表9
第一组 | 第二组 | 第三组 | |
肉毒碱棕榈酰转移酶Ⅱ(肝脏) | 1 | 0.9081 | 1.66 |
肉毒碱棕榈酰转移酶Ⅱ(附睾) | 1 | 0.188 | 0.6933 |
因此,可知,LM1019菌株具有促进肥胖抑制基因的表达的效果。
肝脏中的肥胖相关基因表达减少
当进行肉毒碱棕榈酰转移酶基因表达实验时,利用与所制备的RNA互补的DNA并通过实时聚合酶链式反应确认作为肝脏内肥胖相关基因的硬脂酰辅酶A去饱和酶1(SCD1)、脂肪酸合酶(FAS)及胆固醇调节元件结合蛋白1(SREBP1)的表达。
硬脂酰辅酶A去饱和酶1(Stearoyl-CoA desaturase-1,SCD1)为将单不饱和脂肪酸的合成用作媒介的酶,在肥胖人士中的表达量高,与遗传性肥胖患者或2型糖尿病患者所具有的脂肪代谢的功能障碍有关。
脂肪酸合酶(Fatty-acid Synthase,FAS)为脂肪酸合成酶,为生成细胞内脂肪的必要条件。若其的表达增加,则可解释为细胞内脂肪合成增加。
胆固醇调节元件结合蛋白1(Sterol regulatory element-bindingtranscription factor 1,SREBP1)为调节脂肪合成的结合蛋白酶,此基因也与所述两个基因一同影响脂肪合成,随着数值的增加堆积体脂。
下述表10为用于实验的引物,36B4基因的mRNA表达为内部对照组(internalcontrol)。
表10
如图8所示,在肝脏确认硬脂酰辅酶A去饱和酶1、脂肪酸合酶、胆固醇调节元件结合蛋白1基因的表达的结果,可确认,相比于第二组,作为实验组的第三组的表达量减少。对此适用36B4,在表11示出2^-ddCt的平均数值。
表11
第一组 | 第二组 | 第三组 | |
硬脂酰辅酶A去饱和酶1 | 1 | 2.238 | 1.098 |
脂肪酸合酶 | 1 | 1.779 | 1.366 |
胆固醇调节元件结合蛋白1 | 1 | 2.052 | 1.643 |
因此,可确认,LM1019菌株具有抑制参与脂肪合成的基因的表达的效果。
1当适用条款6.4(d)时、原始保藏日是指已获得作为国际保藏单位的状态的日期
格式BP/4
PCT/RO/134表
Claims (9)
1.一种鼠李糖乳杆菌LM1019菌株,其特征在于,保藏编号为KCCM12308P。
2.一种鼠李糖乳杆菌LM1019,其特征在于,具有同时预防或治疗肥胖及糖尿病的功效,保藏编号为KCCM12308P。
3.一种用于预防或治疗肥胖或糖尿病的药学组合物,其特征在于,包含鼠李糖乳杆菌LM1019菌株,保藏编号为KCCM12308P,所述鼠李糖乳杆菌LM1019菌株在小肠细胞或消化道同时具有脂解抑制效果及食欲调节效果。
4.根据权利要求3所述的用于预防或治疗肥胖或糖尿病的药学组合物,其特征在于,脂解抑制通过抑制脂肪酶的活性来实现。
5.根据权利要求3所述的用于预防或治疗肥胖或糖尿病的药学组合物,其特征在于,食欲调节通过减少瘦素激素的分泌来实现。
6.根据权利要求3所述的用于预防或治疗肥胖或糖尿病的药学组合物,其特征在于,所述鼠李糖乳杆菌LM1019菌株减少胰岛素抗性。
7.一种用于预防或改善肥胖或糖尿病的食品组合物,其特征在于,包含鼠李糖乳杆菌LM1019菌株,保藏编号为KCCM12308P,所述鼠李糖乳杆菌LM1019菌株在小肠细胞或消化道同时具有脂解抑制效果及食欲调节效果。
8.根据权利要求7所述的用于预防或改善肥胖或糖尿病的食品组合物,其特征在于,所述食品组合物为健康功能食品、乳制品、发酵制品或食品添加剂。
9.一种用于预防或改善肥胖或糖尿病的动物饲料组合物,其特征在于,包含鼠李糖乳杆菌LM1019菌株,保藏编号为KCCM12308P,所述鼠李糖乳杆菌LM1019菌株在小肠细胞或消化道同时具有脂解抑制效果及食欲调节效果。
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CN116694537B (zh) * | 2023-07-28 | 2023-10-31 | 善恩康生物科技(苏州)有限公司 | 鼠李糖乳酪杆菌及其在制备治疗2型糖尿病产品中的应用 |
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US20210106630A1 (en) | 2021-04-15 |
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