血液反式脂肪酸、氨基酸及脂肪因子水平与慢性代谢性疾病的人群关联研究
文献类型：学位论文
| 作者 | 俞丹霞 |
| 学位类别 | 博士 |
| 答辩日期 | 2012-05 |
| 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 | 反式脂肪酸 氨基酸 脂肪因子 代谢综合症 2型糖尿病 |
| 其他题名 | The Associations of Metabolic Diseases with Circulating Levels of Trans-fatty Acids, Amino Acids and Adipokines |
| 学位专业 | 生物化学与分子生物学 |
| 中文摘要 | 研究背景和目的： 近几十年，我国居民的膳食结构、营养状况和生活方式都发生了巨大的变迁。在人们生活水平不断提高的同时，我国慢性代谢性疾病，如代谢综合症和2型糖尿病的患病率也急剧上升，严重威胁着人们的生命健康，并带来沉重的经济损失和社会压力。来自西方人群的研究提示，膳食反式脂肪酸可能是糖脂代谢紊乱的重要危险因素，但工业生成和天然来源的反式脂肪酸是否同样危害健康尚无定论。并且，对于有着传统膳食结构的中国人群，至今仍缺乏关于反式脂肪酸摄入量、种类、食物来源及其与慢性代谢性疾病关系的报道。另一方面，最近的代谢组学研究提示，氨基酸代谢异常与肥胖相关的慢性代谢性疾病显著相关。然而，已有的人群研究样本量较小，结论存在差异，并且缺乏合理控制了其它相关风险因素的研究数据。最后，多种血浆脂肪因子，包括瘦素、可溶性瘦素受体、高分子量脂联素与代谢综合症在中国人群中的关联关系未得到证实，且这些关系是否受到慢性炎症或体脂含量及分布的影响也需要进一步的研究。 本论文拟从以上3个方面，结合膳食摄入、生活方式及多方面的疾病风险因素，考察血液反式脂肪酸生物标记物、氨基酸谱及多种脂肪因子水平与代谢综合症或2型糖尿病患病风险的关联关系，并进一步探讨这些关系的潜在机制和影响因素，为中国人群慢性代谢性疾病预防与治疗提供科学依据。 研究内容和方法： 本研究采用人群流行病学调查设计，借助多种高通量高灵敏度的检测手段： 1) 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”的北京和上海3107名50-70岁男女性的血液红细胞膜脂肪酸组成； 2) 借助气相色谱-质谱联用平台检测了参加“营养、肠道菌群与肥胖关系的病例-对照研究”1035名35-54岁上海男女性的血浆氨基酸组成； 3) 用酶联免疫吸附法测定了参加“营养、肠道菌群与肥胖关系的病例-对照研究”1055名调查对象的血浆瘦素、可溶性瘦素受体及高分子量脂联素的浓度； 4) 用双能X射线吸收仪测量了部分调查对象的全身脂肪及腹部脂肪的重量和百分比； 5) 在以上2个人群中，我们还用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；我们还对调查对象进行了体格检查，包括身高、体重、腰围、血压等，并检测了多方面的代谢指标，包括空腹血糖、胰岛素、血脂、炎性因子等。 本论文采用生物统计学方法，有机地结合以上数据，考察了红细胞膜反式脂肪酸、血浆氨基酸及其聚类因子、血浆瘦素、可溶性瘦素受体及高分子量脂联素与2型糖尿病或代谢综合症及其组分的关联关系。并探讨了这些关系是否受到全身脂肪、腹部脂肪含量、炎性因子等其它风险因素的调控，及潜在的交互作用。 研究结果： 1) 红细胞膜上总反式18:1脂肪酸及2种反式18:2脂肪酸被定量检测，它们共占全部红细胞膜脂肪酸的0.37%。总反式脂肪酸浓度，女性高于男性，城市居民高于农村居民。反式18:1脂肪酸与膳食奶制品摄入量显著正相关（相关系数=0.27）。控制体质指数（body mass index, BMI）、社会人口统计学、生活方式、多个膳食因素及反式18:2脂肪酸后，红细胞膜反式18:1与代谢综合症风险负相关（四分位最高组与最低组风险比值比OR=0.57，95%置信区间CI：0.44-0.76，趋势P值<.0001），与2型糖尿病风险也呈负相关（OR [95% CI]=0.68 [0.48-0.97], 趋势P值=0.02）。然而，反式18:2脂肪酸与代谢综合症和2型糖尿病风险关系不显著，却与高甘油三酯血症及高低密度脂蛋白血症显著正相关（趋势P值<.0001及=0.03）。 2) 共20种血浆氨基酸被主成分分析法聚类成3个因子。在控制了社会人口统计变量、生活方式及BMI后，支链氨基酸相关因子与2型糖尿病风险显著正相关（OR [95% CI]=4.50 [3.41-5.95]）。然而，另2个氨基酸因子与降低30-50%的2型糖尿病风险显著相关。这些氨基酸因子也关联于腹部脂肪、血脂、炎性因子和脂肪因子水平。进一步控制这些已被证实的风险标记物，氨基酸因子与2型糖尿病的相关关系仍然显著，且可能与炎性因子有交互作用。 3) 血浆高分子量脂联素水平与代谢综合症风险负相关（四分位最高组与最低组OR=0.30，95% CI：0.18-0.50，趋势P值<.0001）。这个负相关关系独立于体脂指数（fat mass index, FMI），炎性因子，瘦素和可溶性瘦素受体水平。血浆可溶性瘦素受体也与代谢综合症负相关，但是在控制高分子量脂联素后，显著性消失（四分位最高与最低组OR [95% CI]=0.78 [0.47-1.32], 趋势P值= 0.15）。相反的是，瘦素与代谢综合症风险呈正相关（四分位最高与最低组OR [95% CI]=2.64 [1.35-5.18], 趋势P值=0.006），此关系独立于炎性因子和另两个脂肪因子，但在控制FMI后显著性消失。 研究结论： 1) 在中国50-70岁中老年人群中，红细胞膜反式脂肪酸总含量较低。反式18:1脂肪酸可能可以作为膳食奶制品摄入的生物标记物。反式18:1脂肪酸与代谢综合症及2型糖尿病风险呈负相关，而反式18:2脂肪酸与血脂异常呈正相关。 2) 在中国35-54岁中年人群中，血浆氨基酸谱与多种代谢紊乱相关，包括胰岛素抵抗、血脂异常、系统炎性、腹型肥胖及脂肪因子异常。氨基酸因子与2型糖尿病风险的显著关联独立于以上代谢表型，可能受炎性水平调控。 3) 在中国35-54岁中年人群中，高分子量脂联素独立于体脂，炎性，瘦素和可溶性瘦素受体与代谢综合症负相关。而瘦素与代谢综合症的正相关关系可能主要由过多的身体脂肪介导。 |
| 索取号 | D2012-041 |
| 英文摘要 | Background and objectives: In recent decades, Chinese people have been undergoing rapid nutrition and lifestyle transitions. Meanwhile, obesity-related metabolic disorders such as metabolic syndrome (MetS) and type 2 diabetes have become major public health challenges in China. Trans-fatty acids (TFAs) were demonstrated to have adverse effects on health in western populations. However, few data are available about the intakes and food sources of TFAs as well as their associations with metabolic outcomes in Asian people who traditionally have a prudent diet. Moreover, the health effects of ruminant-derived TFAs remain controversial. Second, recent advance in metabolomics technologies suggested that dysregulated amino acid metabolism might play a role in the development of type 2 diabetes. However, previous studies were almost conducted with small sample sizes in developed countries. It is not sure whether similar results could be replicated in large cohorts or generalized into Chinese population. Meanwhile, it is not clear whether the associations between specific amino acid profiles and type 2 diabetes are modified by other co-morbidities. Third, little is known regarding the associations between high-molecular-weight (HMW-) adiponectin, leptin and soluble leptin receptor (sOB-R) and MetS in Chinese. Also few studies elucidate the effects of inflammation and body fat mass on these relations. We aimed to investigate the associations of MetS or type 2 diabetes with erythrocyte TFAs, plasma amino acids and adipokines in 2 epidemiological studies among Chinese population. We further explored the potential effect-modifiers or interactions underline these associations with comprehensive adjustment of confounders. Study design and methods: 1) Erythrocyte fatty acids were measured by gas chromatography among 3107 men and women (50-70 years) recruited from urban and rural areas in northern and southern China (the Nutrition and Health of Aging Study). 2) Plasma amino acids were determined by gas chromatography-mass spectrometry among 1035 Chinese men and women aged 35-54 years (the Gut Microbiota and Obesity Study). 3) Plasma HMW-adiponectin, leptin and sOB-R were measured by enzyme-linked immuno sorbent assayes among 1055 participants from the Gut Microbiota and Obesity Study. 4) Body composition, total fat mass/percentage and trunk fat mass/percentage were assessed by dual-energy X-ray absorptiometry. 5) Information on social-demographics (e.g. age, sex, education attainment and family history of chronic diseases), lifestyles (e.g. smoking, alcohol drinking, physical activity, sleep), and detailed food intake was collected by standardized questionnaires. Physical examination was conducted to obtain height, weight, waist circumference and blood pressure. Multiple biomarkers were also assessed, including fasting glucose, insulin, blood lipids and inflammatory markers. MetS was defined by the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian-Americans. Type 2 diabetes was defined by the criteria from American Diabetes Association. Studies were approved by institutional review board of the Institute for Nutritional Sciences and written Informed consents were provided by all participants. Results: 1) Total trans-18:1 and two trans-18:2 isomers were detected and accounted for 0.37% of total fatty acids in erythrocytes. TFAs concentrations were higher in women than men, and in urban than rural residents. Trans-18:1, but not trans-18:2, showed a modest correlation with dairy consumption (r=0.27), but not with other foods. After adjustment for BMI, social-demographic, lifestyle, dietary factors and other TFAs, erythrocyte trans-18:1 was inversely associated with risks of MetS (odds ratio [OR]: 0.57, 95% confidence interval [CI]: 0.44-0.76, Ptrend<0.0001) and type 2 diabetes (OR [95% CI]=0.68 [0.48-0.97], Ptrend=0.02) comparing extreme quartiles. In contrast, trans-18:2 were positively associated with high triglycerides (Ptrend<0.0001) and LDL (Ptrend=0.03), although the associations with MetS or diabetes were not significant. 2) A branched-chain amino acid (BCAA)-related factor was associated with higher risk of diabetes after adjustment for socio-demographics, lifestyles and BMI (OR [95% CI]=4.50 [3.41-5.95]). Whereas, the other 2 amino acid factors were associated with 30-50% lower risks of diabetes. These factors were also significantly correlated with trunk fat, blood lipids, inflammatory and adipose cytokines. Nevertheless, the associations between amino acid factors and diabetes remained significant after controlling these established biomarkers, and might be modified by CRP levels. 3) HMW-adiponectin was inversely associated with MetS in multivariate model including fat mass index (FMI), inflammatory markers, leptin and sOB-R (OR [95% CI]=0.30 [0.18-0.50] in the highest quartile, Ptrend<.0001). Plasma sOB-R was also inversely associated with MetS independent of body fatness and inflammatory markers, whereas the association was somewhat attenuated after adjusting HMW-adiponectin (OR [95% CI]=0.78 [0.47-1.32] in the highest quartile, Ptrend=0.15). In contrast, leptin was associated with increased odds of MetS independent of inflammatory markers, HMW-adiponectin, and sOB-R (OR [95% CI]=2.64 [1.35-5.18] in the highest quartile, Ptrend=0.006), although further adjustment for FMI abolished this association. Conclusions: 1) In this middle-aged and older Chinese with overall low erythrocyte TFAs levels, trans-18:1, but not trans-18:2, may serve as a marker of dairy intake. Higher trans-18:1 was associated with lower risks of MetS and type 2 diabetes, whereas higher trans-18:2 were associated with dyslipidemia. 2) Plasma amino acid profiles were associated with multiple disorders involved in insulin resistance, dyslipidemia, inflammation, abdominal obesity and abnormal adipokines. Their associations with type 2 diabetes were robust and independent of these conventional risk factors and might be affected by inflammatory status. 3) HMW-adiponectin exhibited strong inverse associations with MetS independent of body composition, inflammation, leptin and sOB-R; while the associations of leptin and sOB-R were largely explained by fat mass or HMW-adiponectin, respectively. |
| 语种 | 中文 |
| 公开日期 | 2015-12-24 |
| 源URL | [http://202.127.25.144/handle/331004/265]  |
| 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 | 俞丹霞. 血液反式脂肪酸、氨基酸及脂肪因子水平与慢性代谢性疾病的人群关联研究[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. 2012. |
入库方式： OAI收割
来源：上海营养与健康研究所
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