Mobilization of pro-inflammatory lipids in obese Plscr3-deficient mice.
Mobilization of pro-inflammatory lipids in obese Plscr3-deficient mice.
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DOI：
10.1186/gb-2007-8-3-r38
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发表时间：
2007
期刊：
影响因子：
12.3
通讯作者：
Siuzdak G
中科院分区：
文献类型：
--
作者：
Mutch DM;O'Maille G;Wikoff WR;Wiedmer T;Sims PJ;Siuzdak G
缺乏磷脂酶3的小鼠的代谢谱揭示了肥胖和炎症之间可能的分子联系。肥胖症的流行促使人们寻找能够影响脂肪功能的候选基因。其中一个候选者，编码磷脂扰码酶3（PLSCR 3），最近被确定，因为它的基因缺失导致腹部脂肪垫中的脂质积累和代谢综合征的特征性变化。由于脂肪组织越来越多地被认为是一种内分泌器官，能够释放调节不同生理过程的小分子，我们检查了野生型、Plastom 1-/-、Plastom 3-/-和Plastom1&3-/-小鼠的血浆。使用结合靶向基因表达分析的非靶向综合代谢物分析方法，评估PLSCR蛋白质的扰动生物化学和功能冗余。在Plastic 3-/-和Plastic1&3-/-动物中，19种代谢物受到差异和相似的调节，其中5种通过精确的质谱、串联质谱数据及其与Metlin数据库的相关性表征为富含C16：1、C18：1、C20：3、C20：5和C22：5脂肪酸的溶血磷脂酰胆碱（LPC）物质。在消除PLSCR 1后，未检测到血浆代谢组的显著变化，表明促炎性脂质的增加与PLSCR 3缺陷动物的肥胖状态特异性相关。相应地，白色脂肪生成基因表达的增加证实了PLSCR 3在脂肪脂质代谢中的作用。循环代谢物的非靶向分析表明PLSCR蛋白之间没有可检测的功能冗余;然而，这种方法同时鉴定了以前未被识别的脂质代谢物，这些脂质代谢物表明肥胖、炎症和与PLSCR 3缺陷相关的下游后果之间存在新的分子联系。
Metabolic profiling of mice deficient in phospholipid scramblase 3 reveals a possible molecular link between obesity and inflammation. The obesity epidemic has prompted the search for candidate genes capable of influencing adipose function. One such candidate, that encoding phospholipid scramblase 3 (PLSCR3), was recently identified, as genetic deletion of it led to lipid accumulation in abdominal fat pads and changes characteristic of metabolic syndrome. Because adipose tissue is increasingly recognized as an endocrine organ, capable of releasing small molecules that modulate disparate physiological processes, we examined the plasma from wild-type, Plscr1-/-, Plscr3-/- and Plscr1&3-/- mice. Using an untargeted comprehensive metabolite profiling approach coupled with targeted gene expression analyses, the perturbed biochemistry and functional redundancy of PLSCR proteins was assessed. Nineteen metabolites were differentially and similarly regulated in both Plscr3-/- and Plscr1&3-/- animals, of which five were characterized from accurate mass, tandem mass spectrometry data and their correlation to the Metlin database as lysophosphatidylcholine (LPC) species enriched with C16:1, C18:1, C20:3, C20:5 and C22:5 fatty acids. No significant changes in the plasma metabolome were detected upon elimination of PLSCR1, indicating that increases in pro-inflammatory lipids are specifically associated with the obese state of Plscr3-deficient animals. Correspondingly, increases in white adipose lipogenic gene expression confirm a role for PLSCR3 in adipose lipid metabolism. The untargeted profiling of circulating metabolites suggests no detectable functional redundancies between PLSCR proteins; however, this approach simultaneously identified previously unrecognized lipid metabolites that suggest a novel molecular link between obesity, inflammation and the downstream consequences associated with PLSCR3-deficiency.
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影响因子：
4.5
作者：
Mutch DM;Clément K
通讯作者：
Clément K
影响因子：
4.3
作者：
Chuang, LT;Thurmond, JM;Huang, YS
通讯作者：
Huang, YS
影响因子：
1.9
作者：
Engler, MM;Bellenger-Germain, SH;Poisson, JPG
通讯作者：
Poisson, JPG
DOI：
10.1073/pnas.132384699
发表时间：
2002-08-20
影响因子：
11.1
作者：
Ntambi, JM;Miyazaki, M;Attie, AD
通讯作者：
Attie, AD
影响因子：
2.8
作者：
Fuchs, B;Schiller, E;Arnold, K
通讯作者：
Arnold, K