Metabolic profiling reveals distinct variations linked to nicotine consumption in humans--first results from the KORA study.
Metabolic profiling reveals distinct variations linked to nicotine consumption in humans--first results from the KORA study.
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DOI：
10.1371/journal.pone.0003863
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发表时间：
2008
期刊：
影响因子：
3.7
通讯作者：
Illig, Thomas
中科院分区：
文献类型：
--
作者：
Wang-Sattler, Rui;Yu, Yao;Mittelstrass, Kirstin;Lattka, Eva;Altmaier, Elisabeth;Gieger, Christian;Ladwig, Karl H.;Dahmen, Norbert;Weinberger, Klaus M.;Hao, Pei;Liu, Lei;Li, Yixue;Wichmann, H. -Erich;Adamski, Jerzy;Suhre, Karsten;Illig, Thomas
在吸烟过程中暴露于尼古丁会导致许多代谢变化，而这些变化目前尚不清楚。我们定量分析了来自奥格斯堡地区KORA （Cooperative Health Research in Region of Augsburg）人类队列的283份血清样本中的198种代谢物。代谢谱的多变量分析表明，吸烟者组与戒烟者和非吸烟者组可以明显区分。此外，23种脂质代谢物被鉴定为尼古丁依赖的生物标志物。除了三种酰基-烷基-磷脂酰胆碱（如磷脂原）外，这些生物标志物的水平在吸烟者中均高于戒烟者和非吸烟者。我们进一步发现，在吸烟者中，脂质与二酰基磷脂酰碱的比值降低，并受到烷基甘油磷酸合成酶（烷基- dhap）在醚脂质和甘油磷脂途径中的调节。值得注意的是，我们的代谢物谱与在一项分析人类肺组织基因表达的研究中发现的吸烟者的烷基- dhap （AGPS）基因的强烈下调一致。我们的数据表明，吸烟与浆氧原缺乏症有关，这是由过氧化物酶烷基- dhap活性降低或缺乏引起的。我们的发现为吸烟成瘾的病理生理学提供了新的见解。小分子激活烷基dhap酶可能为治疗提供新的途径。
Exposure to nicotine during smoking causes a multitude of metabolic changes that are poorly understood. We quantified and analyzed 198 metabolites in 283 serum samples from the human cohort KORA (Cooperative Health Research in the Region of Augsburg). Multivariate analysis of metabolic profiles revealed that the group of smokers could be clearly differentiated from the groups of former smokers and non-smokers. Moreover, 23 lipid metabolites were identified as nicotine-dependent biomarkers. The levels of these biomarkers are all up-regulated in smokers compared to those in former and non-smokers, except for three acyl-alkyl-phosphatidylcholines (e.g. plasmalogens). Consistently significant results were further found for the ratios of plasmalogens to diacyl-phosphatidylcolines, which are reduced in smokers and regulated by the enzyme alkylglycerone phosphate synthase (alkyl-DHAP) in both ether lipid and glycerophospholipid pathways. Notably, our metabolite profiles are consistent with the strong down-regulation of the gene for alkyl-DHAP (AGPS) in smokers that has been found in a study analyzing gene expression in human lung tissues. Our data suggest that smoking is associated with plasmalogen-deficiency disorders, caused by reduced or lack of activity of the peroxisomal enzyme alkyl-DHAP. Our findings provide new insight into the pathophysiology of smoking addiction. Activation of the enzyme alkyl-DHAP by small molecules may provide novel routes for therapy.
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影响因子：
14.9
作者：
Kanehisa M;Araki M;Goto S;Hattori M;Hirakawa M;Itoh M;Katayama T;Kawashima S;Okuda S;Tokimatsu T;Yamanishi Y
通讯作者：
Yamanishi Y
影响因子：
4.5
作者：
Ferrara CT;Wang P;Neto EC;Stevens RD;Bain JR;Wenner BR;Ilkayeva OR;Keller MP;Blasiole DA;Kendziorski C;Yandell BS;Newgard CB;Attie AD
通讯作者：
Attie AD
影响因子：
3.1
作者：
Gochman, Einat;Reznick, Abraham Z.;Levy, Yishai
通讯作者：
Levy, Yishai
DOI：
10.1016/0002-9378(84)90156-x
发表时间：
1984-01-01
影响因子：
9.8
作者：
MOCHIZUKI, M;MARUO, T;OHTSU, T
通讯作者：
OHTSU, T
影响因子：
9.9
作者：
通讯作者：
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