（08.30 --09.05/ 2010）
美寶國際集團(tuán):陶國新 

　　本周動(dòng)態(tài)包括以下內(nèi)容： 脂肪可用作細(xì)胞內(nèi)在 pH 感受器； 魚油抗炎抗糖尿病的機(jī)理；發(fā)現(xiàn)上皮組織中神秘免疫細(xì)胞的功能和機(jī)理； 蛋白質(zhì) TIMP3 促進(jìn)造血干細(xì)胞分裂； 中草藥提取物 大黃素 改善糖尿病和胰島素抵抗的機(jī)理； 共生菌群失調(diào)或?qū)е麓x性疾病。

•  脂肪可用作細(xì)胞內(nèi)在 pH 感受器
【摘要】 來源：《科學(xué)》 發(fā)布時(shí)間： 2010-8-30 16:44:36

　　英國哥倫比亞大學(xué)（ UBC ）的一個(gè)研究小組發(fā)現(xiàn)細(xì)胞膜上存在的一種特異的脂肪可作為一種細(xì)胞 pH 感受器。該研究成果被發(fā)表在《科學(xué)》（ Science ）雜志上。 pH 值是對(duì)酸度或堿度的一種測(cè)量值。細(xì)胞需要維持 pH 穩(wěn)定以保證身體正常的細(xì)胞功能。然而細(xì)胞 pH 監(jiān)視器的機(jī)制卻不清楚?！翱茖W(xué)家們發(fā)現(xiàn)一些特異的蛋白可以檢測(cè)某些環(huán)境下 pH 值的改變，”英國哥倫比亞大學(xué)醫(yī)學(xué)院細(xì)胞及生理學(xué)科系的副教授、生命科學(xué)研究所的成員 Chris Loewen 說：“我們發(fā)現(xiàn)一種存在于所有細(xì)胞中稱為磷脂酸的特異性磷脂，能夠檢測(cè)細(xì)胞中 pH 值的變化?！薄笆褂冕劸平湍缸鳛槟Ｐ?，我們發(fā)現(xiàn)當(dāng)被剝奪營養(yǎng)素時(shí)，細(xì)胞的 pH 值下降可影響磷脂酸的化學(xué)狀態(tài)，從而改變基因表達(dá)和細(xì)胞新陳代謝。”英國哥倫比亞大學(xué)和溫哥華沿岸衛(wèi)生研究所的成員 Loewen 說。

  　　新的發(fā)現(xiàn)具有非常重要的意義，它有助于研究者了解人類新陳代謝和疾病，因?yàn)樗猩矬w的脂類結(jié)構(gòu)和功能都是非常相似的?？蓪⑵溥\(yùn)用到其他領(lǐng)域進(jìn)行更深的探究，例如腫瘤發(fā)生——因?yàn)榱字岷?pH 值在這一過程中發(fā)揮了非常重要的作用。亦可應(yīng)用到大腦研究，腦細(xì)胞 pH 值的動(dòng)態(tài)改變表明他們也使用了 pH 感受器。

【點(diǎn)評(píng)】

　　發(fā)現(xiàn)磷脂酸可以檢測(cè)細(xì)胞內(nèi) pH 值的變化并調(diào)節(jié)與效應(yīng)蛋白的結(jié)合，從而調(diào)節(jié)機(jī)體生理活動(dòng)。鑒于 pH 值的穩(wěn)定對(duì)生物體生存的重要意義，作為細(xì)胞內(nèi) pH 值感受器的功能會(huì)極大地提高磷脂酸這類脂質(zhì)在生物體中的重要性。

【原文摘錄】   Science Vol. 329. no. 5995, pp. 1085 – 1088, DOI: 10.1126/science.1191026

Phosphatidic Acid Is a pH Biosensor That Links Membrane Biogenesis to Metabolism

Barry P. Young, John J. H. Shin, Rick Orij, et al.

Recognition of lipids by proteins is important for their targeting and activation in many signaling pathways, but the mechanisms that regulate such interactions are largely unknown. Here, we found that binding of proteins to the ubiquitous signaling lipid phosphatidic acid (PA) depended on intracellular pH and the protonation state of its phosphate head group. In yeast, a rapid decrease in intracellular pH in response to glucose starvation regulated binding of PA to a transcription factor, Opi1, that coordinately repressed phospholipid metabolic genes. This enabled coupling of membrane biogenesis to nutrient availability.

•  魚油抗炎抗糖尿病的機(jī)理

【摘要】

　　ω-3 脂肪酸具有抗炎作用，但機(jī)理一直不清楚。美國加州大學(xué)的研究人員最近發(fā)現(xiàn) G 蛋白偶聯(lián)受體 GPR120 是 ω-3 脂肪酸的受體 / 感受器，體外細(xì)胞試驗(yàn)顯示 GPR120 受到 ω-3 脂肪酸或化學(xué)激動(dòng)劑的刺激會(huì)產(chǎn)生廣泛的抗炎作用，而敲除 GPR120 會(huì)使所有這些作用消失。肥胖癥胰島素抗性的一個(gè)關(guān)鍵機(jī)理是巨噬細(xì)胞介導(dǎo)的慢性組織發(fā)炎。通過喂食野生型和敲除 GPR120 的肥胖小鼠添加或不添加 ω-3 脂肪酸的高脂肪飲食，發(fā)現(xiàn)給野生型小鼠添加 ω-3 脂肪酸可以抑制發(fā)炎并增強(qiáng)全身胰島素敏感性，而在敲除 GPR120 的小鼠則無此效果。因此， ω-3 脂肪酸通過激活 GPR120 受體及其介導(dǎo)的抑制巨噬細(xì)胞介導(dǎo)的慢性組織發(fā)炎的作用而發(fā)揮體內(nèi)增強(qiáng)胰島素敏感性抗糖尿病的作用。

【點(diǎn)評(píng)】
　　魚油，尤其是其富含的 ω-3 脂肪酸的保健作用的機(jī)理一致不太清楚，本文的研究結(jié)果在細(xì)胞和動(dòng)物實(shí)驗(yàn)層面上解釋了 ω-3 脂肪酸的抗炎和抗糖尿病作用機(jī)理，如果同樣的效果可以在臨床試驗(yàn)中重現(xiàn)，那對(duì)于糖尿病和相關(guān)炎癥可能會(huì)提供一種簡(jiǎn)單的食療方案。

【原文摘錄】   Cell , 2010; 142 (5): 687-698 DOI: 10.1016/j.cell.2010.07.041

GPR120 Is an Omega-3 Fatty Acid Receptor Mediating Potent Anti-inflammatory and Insulin-Sensitizing Effects .

Da Young Oh, Saswata Talukdar, Eun Ju Bae, et al.

Omega-3 fatty acids (ω-3 FAs), DHA and EPA, exert anti-inflammatory effects, but the mechanisms are poorly understood. Here, we show that the G protein-coupled receptor 120 (GPR120) functions as an ω-3 FA receptor/sensor. Stimulation of GPR120 with ω-3 FAs or a chemical agonist causes broad anti-inflammatory effects in monocytic RAW 264.7 cells and in primary intraperitoneal macrophages. All of these effects are abrogated by GPR120 knockdown. Since chronic macrophage-mediated tissue inflammation is a key mechanism for insulin resistance in obesity, we fed obese WT and GPR120 knockout mice a high-fat diet with or without ω-3 FA supplementation. The ω-3 FA treatment inhibited inflammation and enhanced systemic insulin sensitivity in WT mice, but was without effect in GPR120 knockout mice. In conclusion, GPR120 is a functional ω-3 FA receptor/sensor and mediates potent insulin sensitizing and antidiabetic effects in vivo by repressing macrophage-induced tissue inflammation.

•  發(fā)現(xiàn)上皮組織中神秘免疫細(xì)胞的功能和機(jī)理

　　【摘要】 9 月 3 號(hào)的 Science 雜志發(fā)表了 Scripps Research Institute 團(tuán)隊(duì)的相關(guān)研究，闡明了皮膚和其他上皮組織中的一種免疫細(xì)胞 γδ T 細(xì)胞的激活機(jī)理。這些免疫細(xì)胞在識(shí)別上皮組織的損傷和病變中起獨(dú)特而關(guān)鍵的作用。自發(fā)現(xiàn) γδ T 細(xì)胞近三十年來，對(duì)其激活機(jī)理一直知之甚少。科學(xué)家發(fā)現(xiàn)這類細(xì)胞出現(xiàn)于胚胎發(fā)育早期的胸腺中，而后遷移到上皮組織中。與免疫系統(tǒng)的 αβT 細(xì)胞不同，大部分 γδ T 細(xì)胞不在血流中循環(huán)，而是作為皮膚、肺和腸的一種主要的 T 細(xì)胞定居在那里并監(jiān)視臨近上皮細(xì)胞的損傷和病變。而 Havran 領(lǐng)導(dǎo)的研究發(fā)現(xiàn) γδ T 細(xì)胞能加速傷口愈合， 跟進(jìn)的研究證實(shí)作為上皮中主要細(xì)胞類型的角質(zhì)細(xì)胞感知皮膚損傷并表達(dá)一種抗原， γδ T 細(xì)胞能夠識(shí)別這種抗原進(jìn)而活化變形成為圓形小工廠，開始大量生產(chǎn)一種生長(zhǎng)因子，這些生長(zhǎng)因子結(jié)合到角質(zhì)細(xì)胞和其他上皮細(xì)胞，促進(jìn)它們?cè)鲋骋蚤]合傷口。 γδ T 細(xì)胞本身也增殖來增強(qiáng)傷口愈合反應(yīng)。

【點(diǎn)評(píng)】

　　γδ T 細(xì)胞促進(jìn)上皮組織傷口愈合的功能和機(jī)理的闡明，會(huì)促進(jìn)對(duì)于免疫細(xì)胞在創(chuàng)傷愈合中的作用的更深入研究，對(duì)于進(jìn)一步理解創(chuàng)傷愈合并開發(fā)更好的治療手段有很大幫助。

【原文摘錄】   Science , 2010; 329 (5996): 1205-1210 DOI: 10.1126/science.1192698

The Junctional Adhesion Molecule JAML Is a Costimulatory Receptor for Epithelial γδ T Cell Activation .

Deborah A. Witherden, Petra Verdino, Stephanie E, et al.

T cells present in epithelial tissues provide a crucial first line of defense against environmental insults, including infection, trauma, and malignancy, yet the molecular events surrounding their activation remain poorly defined. Here we identify an epithelial T cell–specific costimulatory molecule, junctional adhesion molecule–like protein (JAML). Binding of JAML to its ligand Coxsackie and adenovirus receptor (CAR) provides costimulation leading to cellular proliferation and cytokine and growth factor production. Inhibition of JAML costimulation leads to diminished T cell activation and delayed wound closure akin to that seen in the absence of T cells. Our results identify JAML as a crucial component of epithelial T cell biology and have broader implications for CAR and JAML in tissue homeostasis and repair.

4. 蛋白質(zhì) TIMP3 促進(jìn)造血干細(xì)胞分裂
【摘要】 新華網(wǎng) 2010-8-31 9:20:54

　　一項(xiàng)新研究發(fā)現(xiàn)，一種蛋白質(zhì)能夠促進(jìn)造血干細(xì)胞增殖并形成血液細(xì)胞，因此這種蛋白質(zhì)有可能用來制作藥劑，以用于恢復(fù)因放化療而減少的白細(xì)胞和紅細(xì)胞。造血干細(xì)胞是指骨髓中的干細(xì)胞，具有自我復(fù)制能力，且可以分裂形成白細(xì)胞、紅細(xì)胞和血小板等。但造血干細(xì)胞通常只有很少一部分緩慢分裂，大部分幾乎都處于 “ 冬眠狀態(tài) ” 。人體因化療和放療導(dǎo)致血液細(xì)胞減少后，造血干細(xì)胞會(huì)開始分裂，但其機(jī)制一直沒有弄清。日本慶應(yīng)義塾大學(xué)副教授中島秀明等人在 27 日的美國《血液》月刊上發(fā)表論文說，他們?cè)趧?dòng)物實(shí)驗(yàn)中發(fā)現(xiàn)，老鼠進(jìn)行化療和放療后，骨髓中稱為 “TIMP3” 的蛋白質(zhì)增加。而在培養(yǎng)皿中，向采自老鼠骨髓的造血干細(xì)胞添加 “TIMP3” 蛋白質(zhì)進(jìn)行培養(yǎng)后，發(fā)現(xiàn)造血干細(xì)胞增殖活躍，數(shù)量相當(dāng)于未添加時(shí)的 1.5 倍至 2 倍，血液細(xì)胞也隨之增加。研究人員還發(fā)現(xiàn)，如果使老鼠體內(nèi)無法生產(chǎn) “TIMP3” 蛋白質(zhì)，則血液細(xì)胞減少難以恢復(fù)。而一旦 “TIMP3” 過剩，處于 “ 冬眠 ” 狀態(tài)的造血干細(xì)胞就蘇醒過來，開始分裂。研究人員說，在進(jìn)行化療和放療時(shí)，人體骨髓中的血液細(xì)胞會(huì)受到破壞，從而減少，容易出現(xiàn)感染和 貧血 等問題。如利用 “TIMP3” 蛋白質(zhì)，就有望加快恢復(fù)因化療和放療而減少的血液細(xì)胞，除防止感染外，還可以減少輸血量。

【點(diǎn)評(píng)】

　　老鼠細(xì)胞培養(yǎng)和動(dòng)物實(shí)驗(yàn)顯示 TIMP3 蛋白質(zhì)可以促進(jìn)造血干細(xì)胞分裂增殖，但期望這一蛋白能有助于癌癥的輔助治療，還需進(jìn)一步研究是否在人體中有同樣效果以及如何促進(jìn)在體內(nèi)產(chǎn)生這類蛋白質(zhì)。

【原文摘錄】   Blood DOI 10.1182/blood-2010-01-266528.

TIMP-3 recruits quiescent hematopoietic stem cells into active cell cycle and expands multipotent progenitor pool

Hideaki Nakajima1, Miyuki Ito, David S. Smookler, et al.

Regulating transition of hematopoietic stem cells (HSCs) between quiescent and cycling states is critical for maintaining homeostasis of blood cell production. The cycling states of HSCs are regulated by the extracellular factors such as cytokines and extracellular matrix, however, the molecular circuitry for such regulation remains elusive. Here we show that tissue inhibitor of metalloproteinase-3 (TIMP-3), an endogenous regulator of metalloproteinases, stimulates HSC proliferation by recruiting quiescent HSCs into the cell cycle. Myelosuppression induced TIMP -3 in the bone marrow prior to hematopoietic recovery. Interestingly, TIMP-3 enhanced proliferation of HSCs and promoted expansion of multipotent progenitors, which was achieved by stimulating cell-cycle entry of quiescent HSCs without compensating their long-term repopulating activity. Surprisingly, this effect did not require metalloproteinase inhibitory activity of TIMP-3, and was possibly mediated through a direct inhibition of angiopoietin-1 signaling, a critical mediator for HSC quiescence. Furthermore, BM recovery from myelosuppression was accelerated by overexpression of TIMP-3, and in turn, impaired in TIMP-3-deficient animals. These results suggest that TIMP-3 may act as a molecular cue in response to myelosuppression for recruiting dormant HSCs into active cell cycle, and may be clinically useful for facilitating hematopoietic recovery after chemotherapy or ex vivo expansion of HSCs.

5. 中草藥提取物 大黃素 改善糖尿病和胰島素抵抗的機(jī)理
【摘要】

　　大黃素是一種可自大黃、虎杖等多種中草藥之中提取的天然產(chǎn)物，它在減輕 II 型糖尿病的影響方面顯示出了很大的前途?？怯诒驹隆队幚韺W(xué)期刊》（ British Journal of Pharmacology ）的研究結(jié)果顯示，對(duì)由飲食導(dǎo)致肥胖的小鼠給予大黃素之后，其血糖和血清胰島素濃度降低，其胰島素抵抗得到了改善，從而導(dǎo)致更好的血脂健康水平。同時(shí)它還減輕了小鼠的體重，并減少了其中央體脂。論文主要作者、就職于中國科學(xué)院上海藥物研究所（ Shanghai Institute of Materia Medica, Chinese Academy of Sciences ）的 冷穎 博士說道： “ 如果在人類身上重現(xiàn)這一結(jié)果，所有這些變化都將有益于受 II 型糖尿病或者其他與胰島素抵抗相關(guān)聯(lián)的代謝性疾病影響的病人。 ” 越來越多的研究顯示，一種名為 11β-HSD1 的酶在人體對(duì)飲食中所含糖分的反應(yīng)中扮演了重要角色。當(dāng)一個(gè)人食用含糖食物時(shí)，大量葡萄糖進(jìn)入血液。作為回應(yīng)，人體釋放出胰島素，這種激素會(huì)觸發(fā)各種功能，幫助從血液中清除過量的葡萄糖。然而，人體內(nèi)還有另一系列激素，名為糖皮質(zhì)激素，它們的作用與胰島素正好相反。而這里正是 11β-HSD1 起作用的關(guān)鍵，因?yàn)檫@種酶使糖皮質(zhì)激素的作用能力增加。  

　　該項(xiàng)研究首次表明，大黃素對(duì) 11β-HSD1 來說是一種強(qiáng)有力的選擇性抑制劑，從而能夠有效地限制糖皮質(zhì)激素的作用效果，并改善糖尿病和胰島素抵抗。 冷 博士說： “ 我們的工作顯示，這種中草藥的自然提取物可能指出了一條幫助治療 II 型糖尿病以及其他代謝紊亂的新的途徑。為進(jìn)一步發(fā)展這種途徑，研究人員需要開發(fā)與大黃素作用類似的化學(xué)藥品，看看這些藥品是否可以作為治療藥物使用。 ”

【點(diǎn)評(píng)】

　　中草藥天然提取物作用機(jī)理的逐步闡明，將極大的推動(dòng)中草藥及其天然提取物在現(xiàn)代藥物治療中的作用和重要性，尤其是在西藥特別是化學(xué)合成藥出現(xiàn)后繼乏力的現(xiàn)狀下。

【原文摘錄】   British Journal of Pharmacology DOI: 10.1111/j.1476-5381.2010.00826.x

Emodin, a natural product, selectively inhibits 11β-hydroxysteroid dehydrogenase type 1 and ameliorates metabolic disorder in diet-induced obese mice

Ying Feng, Su-ling Huang, Wei Dou, et al.

BACKGROUND AND PURPOSE 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is an attractive therapeutic target of type 2 diabetes and metabolic syndrome. Emodin, a natural product and active ingredient of various Chinese herbs, has been demonstrated to possess multiple biological activities. Here, we investigated the effects of emodin on 11β-HSD1 and its ability to ameliorate metabolic disorders in diet-induced obese (DIO) mice.

EXPERIMENTAL APPROACH Scintillation proximity assay was performed to evaluate inhibition of emodin against recombinant human and mouse 11β-HSDs. The ability of emodin to inhibit prednisone- or dexamethasone-induced insulin resistance was investigated in C57BL/6J mice and its effect on metabolic abnormalities was observed in DIO mice.

KEY RESULTS Emodin is a potent and selective 11β-HSD1 inhibitor with the IC 50 of 186 and 86 nM for human and mouse 11β-HSD1, respectively. Single oral administration of emodin inhibited 11β-HSD1 activity of liver and fat significantly in mice. Emodin reversed prednisone-induced insulin resistance in mice, whereas it did not affect dexamethasone-induced insulin resistance, which confirmed its inhibitory effect on 11β-HSD 1 in vivo . In DIO mice, oral administration of emodin improved insulin sensitivity and lipid metabolism, and lowered blood glucose and hepatic PEPCK, and glucose-6-phosphatase mRNA.

CONCLUSIONS AND IMPLICATIONS This study demonstrated a new role for emodin as a potent and selective inhibitor of 11β-HSD1 and its beneficial effects on metabolic disorders in DIO mice. This highlights the potential value of analogues of emodin as a new class of compounds for the treatment of metabolic syndrome or type 2 diabetes.

6. 共生菌群失調(diào)或?qū)е麓x性疾病

【摘要】 （來源：文匯報(bào) 許琦敏）

　　吃酸奶、補(bǔ)充益生菌，對(duì)健康好，吃太多肉會(huì)使體內(nèi)產(chǎn)生不少毒素 —— 這是廣告勾勒的臆想，還是真有其事？近年來，科學(xué)家發(fā)現(xiàn)，除了遺傳和不健康的生活方式外， 寄居在人體內(nèi)的共生菌群失調(diào)同樣有可能引發(fā)慢性代謝性疾病，而膳食是調(diào)節(jié)菌群的重要途徑之一。
　　有細(xì)菌入侵，人體就會(huì)發(fā)燒，這是顯而易見的炎癥。不過，人體內(nèi)還存在另一種 “ 溫吞水 ” 般的慢性炎癥。這要從菌群說起。人體腸道中存在大量的共生細(xì)菌，分為革蘭氏陽性菌和革蘭氏陰性菌，后者會(huì)產(chǎn)生內(nèi)毒素，并在菌體死后將其釋放進(jìn)血液。 動(dòng)物研究發(fā)現(xiàn)，高脂肪食物會(huì)改變腸道菌群的構(gòu)成，使革蘭氏陰性菌的比例增高，從而導(dǎo)致血液中的內(nèi)毒素濃度升高。而內(nèi)毒素又會(huì)通過一系列反應(yīng)，開啟人體中的炎癥通道，讓人體處于慢性炎癥狀態(tài)中 ，這就好比對(duì)免疫系統(tǒng)的游擊戰(zhàn)，日積月累會(huì)令機(jī)體疲于應(yīng)對(duì)，無法進(jìn)行正常的新陳代謝，肥胖、糖尿病、心血管疾病等代謝性疾病就不請(qǐng)自來了。

　　菌群的變化是否同樣影響著中國人的健康呢？中科院上海生科院營養(yǎng)科學(xué)研究所林旭研究員領(lǐng)導(dǎo)的研究團(tuán)隊(duì)與上海疾控中心合作，通過在上海社區(qū)人群中開展 “ 營養(yǎng)、腸道菌群與肥胖關(guān)系的病例 - 對(duì)照研究 ” 項(xiàng)目，發(fā)現(xiàn) 內(nèi)毒素的結(jié)合蛋白與慢性代謝性綜合征和 2 型糖尿病密切相關(guān) 。 而內(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和代謝紊亂的發(fā)生過程中起到重要作用 。該論文最近發(fā)表于權(quán)威雜志《糖尿病護(hù)理》（ Diabetes Care ）。

　　在這次大規(guī)模人群研究中，科學(xué)家發(fā)現(xiàn)，肥胖個(gè)體中內(nèi)毒素相關(guān)指標(biāo)比正常體重個(gè)體高出 1.76 倍；而且，血漿中內(nèi)毒素相關(guān)指標(biāo)高的個(gè)體，身體中所有 “ 壞分子 ” 、炎癥因子的水平都相應(yīng)偏高，而對(duì)機(jī)體有保護(hù)作用的 “ 好分子 ” 又都偏少。 “ 我們發(fā)現(xiàn)血漿中內(nèi)毒素相關(guān)指標(biāo)的濃度越高，罹患代謝性疾病的風(fēng)險(xiǎn)也越大。 ” 論文主要作者之一、營養(yǎng)所孫亮博士告訴記者，血漿中內(nèi)毒素相關(guān)指標(biāo)最高組的個(gè)體與最低組相比，罹患代謝綜合征的風(fēng)險(xiǎn)高出 2.5 倍、患 2 型糖尿病的風(fēng)險(xiǎn)高出 4.5 倍！

　　這項(xiàng)研究首次在國際上通過較大規(guī)模的人群研究證實(shí)：菌群生物標(biāo)記物與慢性代謝性疾病存在顯著的關(guān)聯(lián)關(guān)系。對(duì)于普通人而言，科學(xué)家提醒說，平時(shí)注意多吃點(diǎn)酸奶、蔬菜，少吃些肉，從菌群調(diào)節(jié)上說，的確會(huì)更有利于健康，在一定程度上減少得代謝性疾病的風(fēng)險(xiǎn)。

【點(diǎn)評(píng)】

　　大規(guī)模人群研究發(fā)現(xiàn)血漿中內(nèi)毒素相關(guān)指標(biāo)的濃度越高，罹患代謝性疾病的風(fēng)險(xiǎn)也越大，菌群生物標(biāo)記物與慢性代謝性疾病存在顯著的關(guān)聯(lián)關(guān)系。調(diào)節(jié)體內(nèi)菌群以有利于健康需要改善飲食結(jié)構(gòu)。

【原文摘錄】   Diabetes Care September 2010 vol. 33 no. 9 1925-1932

A Marker of Endotoxemia Is Associated With Obesity and Related Metabolic Disorders in Apparently Healthy Chinese

Liang Sun , Zhijie Yu , Xingwang Ye , et al.

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 /m 2 ) and 500 normal-weight (18.0 ≤ BMI < 24.0 kg /m 2 ) subjects aged 35–54 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 was defined by the updated National Cholesterol Education Program Adult Treatment Panel III criterion for Asian Americans.

RESULTS LBP levels were significantly higher in overweight/obese individuals than in normal-weight individuals (geometric mean 27.6 [95% CI 25.2–30.3] 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 metabolic syndrome and type 2 diabetes, respectively, comparing the highest with the lowest LBP quartile. Further adjustments for inflammatory markers almost abolished the significant association of LBP with metabolic syndrome but not that with type 2 diabetes, and controlling for adipokines and hepatic enzymes did not substantially alter the results.

CONCLUSIONS Elevated circulating LBP was associated with obesity, metabolic syndrome, 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. Prospective studies are needed to confirm these results.