时间限制性进食在成人和儿童中的相反效应

发布时间：2018-03-15 04:05

本文选题：时间限制性进食　切入点：代谢综合征　出处：《北京协和医学院》2017年博士论文　论文类型：学位论文

【摘要】：研究目的在现代社会,以肥胖、高血脂、胰岛素抵抗、动脉粥样硬化为特征的代谢相关疾病日益严重,给人体健康造成了极大负面影响。通过10年以上的研究,学者们证实时间限制性进食(Time-restricted feeding,TRF)可以预防甚至逆转这些不良健康状况。TRF指的是每天进食限制在8-10小时之间,其余时间无热卡摄入,但每日进食总量不限。这种饮食模式在成人中效果确切,对其机制的研究也逐渐明朗。然而现有研究局限于成人群体,对儿童的研究仍一片空白。考虑到儿童和成人在生理上具有根本性差异,我们认为不可盲目将成人的结论推广至儿童。再加上社会对青少年儿童代谢综合征和营养、饮食等话题的关注,我们设计实验,对该问题进行科学性研究。方法受试小鼠为3周龄,恰离乳。在协和医院动物中心进行1周的适应后,我们将这200只雄性昆明小鼠随机分为TRF模式和普通的随时可进食(Ad libitum,AD)的模式。TRF具体做法:每日23:00将食物放入笼子,次日7:00撤走。小鼠幼年时期为4-8周龄,8周小鼠认为成年。为了方便表达,开始进行进食干预的时间记为0周(4周龄),4周后饮食进行调整,此时小鼠成年,记为4周(8周龄)。实验组小鼠定义为TA:幼年即0-4周TRF,成年后AD;AA:对照组,幼年成年均AD;TT组:幼年成年均TRF。每天纪录每笼小鼠进食量;每周纪录每只小鼠体重;4周和8周时通过血液生化学检测小鼠血糖、血脂、胰岛素、瘦素、饥饿素、GLP-1、性激素等指标;8周时进行肠道菌群和流式细胞分析调节T细胞,以及对肝脏、胰腺、主动脉根部切片染色,进行评估。结果8周后,TA小鼠(幼年TRF,成年AD,即为实验组)体重明显高于对照组,血糖也明显高于对照组。(体重:47.lg vs.45.0g,p0.01;23:00血糖:8.38mmol/L vs.7.99mmol/L,p0.05;次日 7:00:9.72mol/Lvs.9.40mmol/L,p0.05)。与此同时,TA小鼠胰岛素水平和血脂水平却低于对照组:胰岛素:7.199mU/L vs.9.860mU/L,p0.05;甘油三酯 62.92nmol/L vs.83.86nmol/L,p0.05;总胆固醇:19.95mmol/L vs.20.64mmol/L,p = 0.39;低密度脂蛋白:327.87umol/L vs.401.56umol/L,p0.05;高密度脂蛋白:253.04umol/L vs.295.21umol/L,p = 0.13。组织切片发现:TA小鼠有脂肪肝表现;胰岛数量和容量均减少;主动脉根部出现血管壁僵硬、增厚和新生。同时TA小鼠性发育出现滞后,免疫功能下降(6.78%vs.2.69%,p0.01)。结论幼年TRF造成小鼠全面身体机能损伤,包括引起不可逆的代谢紊乱、免疫功能下降、性发育迟缓等。许多证据提示这些损害通过肠道菌群进行作用。一旦这些结论在人群研究身上得到证实,将会成为青少年儿童营养学的有力证据。
[Abstract]:Objective in modern society, metabolic diseases characterized by obesity, hyperlipidemia, insulin resistance and atherosclerosis are becoming more and more serious and have a great negative impact on human health. Researchers have shown that time-restricted feeding TRFs can prevent or even reverse these unhealthy health conditions. TRF refers to a limit of 8 to 10 hours a day, with no caloric intake for the rest of the time. But there is no limit to the amount of food consumed per day. This diet pattern is effective in adults, and studies of its mechanisms are becoming clear. However, current studies are limited to the adult population. The study of children remains blank. Considering the fundamental biological differences between children and adults, we believe that the conclusion of adults should not be blindly extended to children... and that society has metabolic syndrome and nutrition in adolescents and children, Diet and other topics of concern, we designed experiments to carry out a scientific study of the problem. Methods the mice were 3 weeks old and suckled. After one week of adaptation to the animal center of the Concorde Hospital, We randomly divided the 200 male Kunming mice into TRF model and a normal ready to eat ad libitum AD.TRF model: put food in a cage at 23:00 daily. Withdrawal at 7:00 the next day. The mice were considered to be adults in their infancy from 4 to 8 weeks of age. In order to facilitate expression, the time for food intervention was recorded as diet adjustment after 0 weeks and 4 weeks of age, at which time the mice were adults. The mice in the experimental group were defined as TA: TRFs in infancy (0-4 weeks), and in adult mice as control group (ADFTT group): TRFs per cage were recorded every day. Blood glucose, blood lipids, insulin, leptin, hunger GLP-1 and sex hormone were measured by biochemical analysis at 4 and 8 weeks of each mouse body weight every week. At 8 weeks, intestinal flora and flow cytometry were used to regulate T cells. The liver, pancreas and aortic root sections were stained and evaluated. Results after 8 weeks, the body weight of TA mice (juvenile TRFs, adult ADs, experimental groups) was significantly higher than that of the control group. Blood glucose was also significantly higher than that in the control group. (weight: 47.1g vs.45.0 g / L 0.01: 23: 00 Blood glucose: 8.38 mmol / L / L vs.7.99 mmol / L / L = 0.05; next day: 7: 9.72 mol / L vs. 9.40 mmol / L / L / L / L = 9.40 mmol / L / L = 0.055.At the same time, the insulin level and lipid level in TA mice were lower than those in the control group: insulin: 7.199 mUL / L vs.9.860 mU / L P 0.05; triglyceride 62.92 nmol / L vs.83.86 nmol / L; total cholesterol 19.95 mmol / L / L / vs.20.64mmolL / L / P = 0.3939; Lipoprotein: 327.87 umolr / L vs.401.56 umolr / L p 0.05; High-density lipoprotein: 253.04 umolr / L vs.295.21 umoll / L P = 0.13.The tissue sections showed that the mice had fatty liver. The number and volume of islets decreased, vascular wall stiffened, thickened and regenerated at the root of aorta. At the same time, the sexual development of TA mice was delayed, and the immune function was decreased by 6.78vs.2.69p 0.01.Conclusion Juvenile TRF can cause total body function damage in mice. These include irreversible metabolic disorders, decreased immune function, sexual stunting, and so on. There is a lot of evidence that these lesions act through the intestinal flora. Once these findings have been confirmed in population studies, Will be a strong evidence of adolescent nutrition.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R151.4

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