血液脂肪酸标记与慢性代谢性疾病的人群研究
文献类型：学位论文
| 作者 | 宗耕 |
| 学位类别 | 博士 |
| 答辩日期 | 2013-08-01 |
| 授予单位 | 中国科学院上海生命科学研究院营养科学研究所 |
| 授予地点 | 中国科学院上海生命科学研究院 |
| 导师 | 林旭 |
| 关键词 | 脂肪酸生物标记 代谢综合征 糖尿病 中国人群 |
| 其他题名 | The Associations of Fatty Acid Biomarkers with Metabolic disorders in Chinese |
| 学位专业 | 生物化学与分子生物学 |
| 中文摘要 | 研究背景 膳食脂肪酸与慢性代谢性疾病发生存在密切的联系。传统的营养流行病学研究利用膳食问卷收集脂肪酸摄入信息，数据准确性难以保障。已有的研究发现，脂肪酸在体内的含量能够反映膳食中脂肪酸和其它食物的摄入情况。随着高通量检测技术的发展，国外的一些大型队列研究发现多种体内脂肪酸能够预测慢性代谢性疾病的发生。我国传统饮食与西方人群存在较大差异；而过去几十年间，居民膳食结构和慢性代谢性疾病发病发生了巨大变化。国内仍缺乏脂肪酸生物标记与慢性代谢性疾病关系的营养流行病学研究。 研究目的 本论文的一系列工作旨在研究脂肪酸生物标记（种类、总量、比例）与慢性代谢性疾病（如代谢综合征、糖尿病）患病、发病、以及与慢性代谢性疾病发病风险密切相关生理、生化指标的联系；寻找影响中国人群脂肪酸生物标记组成的特有膳食因素，为制定切合我国国情的慢性代谢性疾病预防相关营养政策提供证据。 研究方法 1. 对“中国老龄人口营养健康调查”基线调查对象开展随访，收集6年追踪期间慢代谢性疾病的发病数据；用标准化一般问卷收集了详尽的社会人口统计学信息（如年龄、性别、教育程度等），生活方式信息（如吸烟、饮酒、体力活动和睡眠状况等），以及各种食物摄入量数据；用标准化操作流程对调查对象进行了体格检查，包括身高、体重、腰围、血压等，并检测了空腹血糖、胰岛素、血脂、肝脏酶等指标； 2. 在一项平行设计、随机化临床干预试验中，对189名根据NCEP-ATP III针对亚裔人群修订标准诊断的代谢综合征或者代谢综合征高危人群，给予以美国心脏协会（AHA）健康生活方式指南为依据的生活方式教育和指导，并将他们随机分配到亚麻子干预组（每天食用30克亚麻子）或对照组（无亚麻子干预），进行12周的干预。用酶联免疫吸附法测定多种炎性因子、脂肪因子、细胞黏附因子、氧化应激因子水平； 3. 用气相色谱法定性定量测定了参加“中国老龄人口营养健康调查” 3107 名基线调查对象和完成“亚麻子健康改善项目”189名调查对象的血液红细胞膜脂肪酸组成。 研究结果 1. 红细胞膜棕榈油酸含量与碳水化合物摄入正相关。与红细胞膜棕榈油酸最低四分位相比，最高四分位调查对象患代谢综合征的风险比值比为2.54（95%置信区间为：1.90，3.41），患低高密度脂蛋白血症的风险比值比为2.13 (95%置信区间为：1.66，2.72)，患高血压的风险比值比为1.86 (95%置信区间为：1.41，2.44)，而患高甘油三脂血症的风险比值比则高达到5.95 (95%置信区间为：4.33，8.19)，该关系在控制了多种人口学、生活方式等因素后仍显著（所有线性趋势P值均<0.001）。棕榈油酸与血浆中脂联素存在显著负相关、并与超敏C反应蛋白、视黄醇结合蛋白4、纤溶酶原激活抑制剂1存在显著的正相关。 2. 本研究共在红细胞膜上检测到7种体内脂肪酸合成途径上的脂肪酸，其中C16:0、C16:1n-7、C18:1n-7、C14:0、C16:0与碳水化合物/脂肪摄入的比例正相关，C16:1n-9与蛋白质摄入正相关；没有一种脂肪酸与脂肪摄入正相关。这些脂肪酸与基线、随访时增加代谢性疾病风险的血脂、肝功能指标存在较强的相关关系。此外，C16:1n-7、C16:1n-9、C18:1n-9与随访6年后代谢综合征发病风险存在显著正相关。与这三种脂肪酸最低四分位相比，代谢综合征的发病风险在最高四分位增加了38%到55%；而代谢综合征的发病风险在18:1n-7和14:0最高四分位也显著升高；这些相关关系独立于已知的风险因素及可能的混杂因素。同时，C16:0与C16:1n-7与糖尿病的发病风险存在显著线性正相关；与这两种脂肪酸最低四分位相比，2型糖尿病的发病风险在最高四分位增加了26%到27%。 3. 在代谢综合征患者或高危中国人群中，给予全亚麻子粉膳食干预使EPA在红细胞脂肪酸总量的比例增加了0.13% (95%置信区间：0.08，0.17； P值<0.001），n-3DPA增加0.21%（95%置信区间：0.16，0.27；P值<0.001），总n-6多不饱和脂肪酸与总n-3多不饱和脂肪酸的比例降低（-0.26，95%置信区间：-0.41， -0.11；P值<0.001)，而DHA无显著变化。亚麻子营养干预并未显著改变调查对象血液中炎性因子（C反应蛋白、肿瘤坏死因子α、白细胞介素6、白细胞介素18）、脂肪因子（脂联素、视黄醇结合蛋白4）、内皮功能因子（可溶性细胞粘附因子1、可溶性血管粘附因子1、白细胞趋化蛋白1、E选择素）、血栓形成因子（纤溶酶原激活抑制剂1）、氧化应激因子的水平（氧化低密度脂蛋白）。 4. 红细胞膜上反式18:1脂肪酸异构体的相对含量与奶制品摄入存在较强的正相关（spearman 偏回归系数为0.37，P值<0.001）。该脂肪酸与随访6年后糖尿病的发病相对风险存在显著负相关；而奶制品摄入可能解释了该相关关系。进一步的分析发现，该人群奶制品摄入量较低；而基线奶制品摄入与糖尿病发病风险以及空腹血糖、BMI、腰围、血压在随访期间的变化呈负相关。这些相关关系独立于人口学、生活方式因素；奶制品摄入与糖尿病的负相关在控制血糖变化后线性趋势变弱。 结论 本论文的研究提示：血液中的脂肪酸生物标记与代谢综合征、糖尿病的患病、发病风险存在密切的联系。而中国人群传统膳食结构的特征，如碳水化合物摄入量较高，而脂肪摄入、深海鱼类、奶制品、工业反式脂肪酸摄入低等，是影响该人群体内脂肪酸组成、及其与慢性代谢性疾病关系独特性的最重要因素。相关研究结果仍需要在更具广泛代表性的中国人群研究进一步验证，并需要更多的基础实验证据支持。本研究为发现与我国慢性代谢性疾病发病密切相关的膳食因素提供了重要线索，并为今后制定相关营养政策提供了可靠的基础数据。 |
| 索取号 | D2013-181 |
| 英文摘要 | Background Dietary fat intake has been shown to be associated metabolic disorders. In most of nutritional epidemiological studies, data of fatty acid intake is commonly collected by questionnaires, hence is subjected to recall bias and measurement errors. Numerous studies have found fatty acid in various tissues of human are closely associated dietary intakes of fatty acids and certain food items. With the development of high-throughput detection technology, several large prospective studies have measured fatty acid proportion in biological samples, and found some of the fatty acids were strongly associated with risk of metabolic disorders. The dietary pattern of Chinese is distinctive to those of western populations, and has changed dramatically over the past decades, in companied with overwhelming increases in metabolic diseases. However, epidemiological studies on the associations of fatty acid biomarkers and risk of metabolic diseases are lacking so far. Study aim The series of work in this dissertation aimed to investigate associations of erythrocyte fatty acid biomarkers with risk of metabolic syndrome and diabetes, and various cardiometabolic traits in a prospective study and an intervention study. Potential dietary determinants of fatty acid composition in human body were also explored. Method 1. Participants of the “Nutrition and Health of Aging Population in China (NHAPC)” study were followed up to 6 years. Standard questionnaires were used to collect data of demography, lifestyle, and dietary information. Height, weight, waistline, blood pressure and fasting blood samples were collected during a standardized physical examination. Plasma glucose, insulin, blood lipids, liver enzymes were measured at both baseline and follow-up survey. Most importantly, incident diabetes and metabolic syndrome were indentified. 2. In a paralleled, randomized clinical trial, a total of 189 participants with or at high risk of metabolic syndrome defined by updated NCEP-ATPIII for Asian Americans were provided lifestyle intervention according to AHA guidelines, and then were randomized into 30g/d flaxseed intervention group or control group. The intervention lasted for 12 weeks. Fasting blood samples were collected at the beginning and end of study. Biomarkers of pre-inflammatory status, adipokines, oxidative stress, and endothelial dysfunction were measured by ELISA. 3. Erythrocyte fatty acid composition of participants from both studies was measured by gas chromatograph coupled with mass spectrometer and flame ion detector. Results 1. Erythrocyte palmitoleic acid was positively associated with carbohydrate intake, and metabolic syndrome at the NHAPC baseline survey. Comparing the fourth quartile of palmitoleic acid to the first quartile, odds ratios (95% confidential intervals) were 2.54(1.90, 3.41) for MetS, 2.13(1.66, 2.72) for hypercholesterolemia, 1.86(1.41, 2.44) for hypertension, and 5.95(4.33, 8.19) for hypertriglyceridemia (all Ptrend <0.001). These associations were independent of lifestyle factor and BMI. Besides, palmitoleic acid was correlated with lower plasma levels of adiponectin, and higher high-sensitive C reactive protein, retinol binding protein-4, and plasminogen activator inhibitor-1. 2. In the NHAPC study, seven fatty acids on the de novo lipogenesis (DNL) pathway were indentified on erythrocyte membrane, among which C16:0, C16:1n-7, C18:1n-7, C14:0, and C16:0 were associated a high cabohydrate/fat intake ratio, while C16:1n-9 was associated with high protein intake. None of them was positively associated with fat intake. Baseline DNL fatty acids were associated with deteriorated lipid profile and elevated liver enzymes at both baseline and follow-up. Besides, C16:1n-7, C16:1n-9, and C18:1n-9 were positively associated with risk of MetS, which increased by 38% to 55% comparing extreme quartiles of these fatty acids. Risks of MetS were also significantly higher in the fourth quartiles of C18:1n-7 and C14:0 compa |
| 语种 | 中文 |
| 公开日期 | 2015-12-24 |
| 源URL | [http://202.127.25.144/handle/331004/267]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所_人类营养与疾病研究组 |
| 推荐引用方式 GB/T 7714 | 宗耕. 血液脂肪酸标记与慢性代谢性疾病的人群研究[D]. 中国科学院上海生命科学研究院. 中国科学院上海生命科学研究院营养科学研究所. 2013. |
入库方式： OAI收割
来源：上海营养与健康研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。