近日，Diabetes Care发表了中科院上海生科院营养科学研究所林旭研究员研究团队有关人体内毒素（脂多糖）结合蛋白（LBP）水平与代谢综合征和2型糖尿病患病风险研究的最新发现。
大量的研究表明，慢性炎症有可能是肥胖相关代谢性疾病发生的重要机制之一。然而，迄今为止对引起慢性炎症的诱发因素和相关机理方面仍不清楚。动物实验显示，高脂肪食物或内毒素能激发慢性炎症通路，从而导致代谢性紊乱。
肠道革兰氏阴性菌是内毒素的重要来源。LBP是内毒素通路上的关键分子之一，其半衰期相对较长，检测方法稳定，可以作为反映血液内毒素水平的替代指标。林旭研究组孙亮博士等在超重/肥胖人群(559例)和正常体重人群(500例)系统分析了血浆LBP水平与肥胖及其相关代谢性疾病的关联关系。发现：(1) LBP水平在超重/肥胖个体中显著高于正常体重个体；(2) 血浆LBP水平与体质指数（BMI）、腰围、血压、血糖、血脂、胰岛素等代谢指标，以及肝脏酶、炎性因子和脂肪因子水平显著相关；(3) 在控制了年龄、性别、吸烟、饮酒、体力活动、疾病家族史和BMI后，研究对象罹患代谢综合症、胰岛素抵抗和2型糖尿病的危险性随着血浆LBP水平的升高而显著增加，这些关联还独立于其它危险因素如肝脏酶和脂肪因子水平；(4) 血浆LBP水平与代谢综合征的关联关系与炎症因子水平（C反应蛋白和白介素6）相关，而LBP水平与胰岛素抵抗和2型糖尿病的相关关系却不能完全用炎症因子解释，说明其它机制亦有介入的可能。
本研究首次在较大规模的人群研究中发现LBP与慢性代谢性疾病显著的关联关系，揭示在慢性代谢性疾病发生过程中，菌群产物—内毒素作为一种外源性的诱导物可能在激活慢性炎症通路中起到重要作用。
该项工作得到了中科院知识创新工程重要方向项目、科技部国际科技合作项目、上海市科研计划课题、国家自然科学基金、中科院上海生命科学研究院首席科学家项目以及法国国家研究署的资助。(生物谷www.Bioon.net)
生物谷推荐原文出处：
Diabetes Care doi: 10.2337/dc10-0340
A marker of endotoxemia is associated with obesity and related metabolic disorders in apparently healthy Chinese
Liang Sun, MSc*, Zhijie Yu, MD, PhD*, Xingwang Ye, PhD?, Shurong Zou, MD, MSc?, Huaixing Li, PhD*, Danxia Yu, MSc*, Hongyu Wu, MSc*, Yan Chen, MD, PhD*, Joel Dore, PhD§, Karine Clément, MD, PhD‖?#, Frank B. Hu, MD, PhD** and Xu Lin, MD, PhD
Objective: Elevated lipopolysaccharide-binding protein (LBP), a marker of subclinical endotoxemia, may be involved in the pathogenesis of obesity and metabolic risk. We aimed to investigate the association between plasma LBP and metabolic disorders in apparently healthy Chinese.
Research Design and Methods: A population-based study including 559 overweight/obese (BMI≥24.0 kg/m2) and 500 normal-weight (18.0≤BMI<24.0 kg/m2) subjects aged 35 to 54 years was conducted in Shanghai, China. Fasting plasma glucose, lipid profile, LBP, high-sensitivity C-reactive protein, interleukin-6, high-molecular-weight (HMW)-adiponectin, leptin, hepatic enzymes, and body composition were measured. Metabolic syndrome (MetS) was defined by the updated NCEP/ATPIII criterion for Asian Americans.
Results: LBP levels were significantly higher in overweight/obese than in normal-weight individuals (geometric mean 27.6 (25.2-30.3) μg/ml vs. 10.0 (9.1-11.1) μg/ml; P<0.001). After multiple adjustments including BMI, the odds ratios were 3.54 (95% CI 2.05-6.09) and 5.53 (95% CI 2.64-11.59) for MetS and type 2 diabetes, respectively, comparing the highest with the lowest LBP quartile. Further adjustments for inflammatory markers almost abolished significant association of LBP with MetS, but not with type 2 diabetes while controlling for adipokines and hepatic enzymes did not substantially alter the results.
Conclusions: Elevated circulating LBP was associated with obesity, MetS, and type 2 diabetes in apparently healthy Chinese. These findings suggested a role of lipopolysaccharide via initiation of innate immune mechanism(s) in metabolic disorders.
