近日,，Diabetes Care發(fā)表了中科院上海生科院營養(yǎng)科學(xué)研究所林旭研究員研究團(tuán)隊(duì)有關(guān)人體內(nèi)毒素（脂多糖）結(jié)合蛋白（LBP）水平與代謝綜合征和2型糖尿病患病風(fēng)險(xiǎn)研究的最新發(fā)現(xiàn)。
大量的研究表明,，慢性炎癥有可能是肥胖相關(guān)代謝性疾病發(fā)生的重要機(jī)制之一。然而，迄今為止對引起慢性炎癥的誘發(fā)因素和相關(guān)機(jī)理方面仍不清楚,。動物實(shí)驗(yàn)顯示，高脂肪食物或內(nèi)毒素能激發(fā)慢性炎癥通路,，從而導(dǎo)致代謝性紊亂,。
腸道革蘭氏陰性菌是內(nèi)毒素的重要來源。LBP是內(nèi)毒素通路上的關(guān)鍵分子之一,，其半衰期相對較長,，檢測方法穩(wěn)定，可以作為反映血液內(nèi)毒素水平的替代指標(biāo),。林旭研究組孫亮博士等在超重/肥胖人群(559例)和正常體重人群(500例)系統(tǒng)分析了血漿LBP水平與肥胖及其相關(guān)代謝性疾病的關(guān)聯(lián)關(guān)系,。發(fā)現(xiàn)：(1) LBP水平在超重/肥胖個體中顯著高于正常體重個體；(2) 血漿LBP水平與體質(zhì)指數(shù)（BMI）,、腰圍,、血壓、血糖,、血脂,、胰島素等代謝指標(biāo)，以及肝臟酶,、炎性因子和脂肪因子水平顯著相關(guān),；(3) 在控制了年齡,、性別、吸煙,、飲酒,、體力活動、疾病家族史和BMI后,，研究對象罹患代謝綜合癥,、胰島素抵抗和2型糖尿病的危險(xiǎn)性隨著血漿LBP水平的升高而顯著增加，這些關(guān)聯(lián)還獨(dú)立于其它危險(xiǎn)因素如肝臟酶和脂肪因子水平,；(4) 血漿LBP水平與代謝綜合征的關(guān)聯(lián)關(guān)系與炎癥因子水平（C反應(yīng)蛋白和白介素6）相關(guān),，而LBP水平與胰島素抵抗和2型糖尿病的相關(guān)關(guān)系卻不能完全用炎癥因子解釋，說明其它機(jī)制亦有介入的可能,。
本研究首次在較大規(guī)模的人群研究中發(fā)現(xiàn)LBP與慢性代謝性疾病顯著的關(guān)聯(lián)關(guān)系,，揭示在慢性代謝性疾病發(fā)生過程中，菌群產(chǎn)物—內(nèi)毒素作為一種外源性的誘導(dǎo)物可能在激活慢性炎癥通路中起到重要作用,。
該項(xiàng)工作得到了中科院知識創(chuàng)新工程重要方向項(xiàng)目,、科技部國際科技合作項(xiàng)目、上海市科研計(jì)劃課題,、國家自然科學(xué)基金,、中科院上海生命科學(xué)研究院首席科學(xué)家項(xiàng)目以及法國國家研究署的資助。(生物谷www.Bioon.net)
生物谷推薦原文出處：
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.
