Tissue acylcarnitine status in a mouse model of mitochondrial β-oxidation deficiency during metabolic decompensation due to influenza virus infection.
Tissue acylcarnitine status in a mouse model of mitochondrial β-oxidation deficiency during metabolic decompensation due to influenza virus infection.
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DOI：
10.1016/j.ymgme.2018.06.012
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发表时间：
2018-09
影响因子：
3.8
通讯作者：
McGuire PJ
中科院分区：
文献类型：
--
作者：
Tarasenko TN;Cusmano-Ozog K;McGuire PJ
尽管有明智的监测和护理，但脂肪酸氧化障碍患者可能会因感染而出现代谢失代偿，从而导致横纹肌溶解、心肌病、低血糖和肝功能障碍和衰竭。由于代谢性失代偿的临床研究是危险的，我们采用了感染代谢性失代偿的临床前模型。通过用小鼠适应性流感感染小鼠，并在小鼠长链脂肪酸氧化模型（Acadvl - / -）中使用配对喂养策略，我们的目标是分离感染对组织酰基肉碱的影响，并确定它们与血浆对应物的关系。应用统计数据简化技术（偏最小二乘判别分析，PLS-DA），我们能够识别出驱动实验组所有组织分化的关键酰基肉碱。虽然血浆中与小鼠VLCAD缺乏直接相关的代谢物（如C16和C18）增加，但心脏、肌肉和肝脏等器官也显示出其他途径（如中链FAO和生酮）的参与，这表明有适应性措施。匹配相关分析显示，少量代谢物的血浆和组织水平之间存在很强的相关性（r > 0.7）。总的来说，我们的研究结果表明，感染作为一种应激会产生Acadvl - / -代谢的扰动，这与WT感染和Acadvl - / -对饲对照有很大不同。该模型系统将有助于研究感染对组织代谢的影响，以及评估旨在调节代谢失代偿影响的干预措施。
Despite judicious monitoring and care, patients with fatty acid oxidation disorders may experience metabolic decompensation due to infection which may result in rhabdomyolysis, cardiomyopathy, hypoglycemia and liver dysfunction and failure. Since clinical studies on metabolic decompensation are dangerous, we employed a preclinical model of metabolic decompensation due to infection. By infecting mice with mouse adapted influenza and using a pair-feeding strategy in a mouse model of long-chain fatty acid oxidation (Acadvl−/−), our goals were to isolate the effects of infection on tissue acylcarnitines and determine how they relate to their plasma counterparts. Applying statistical data reduction techniques (Partial Least Squares-Discriminant Analysis, PLS-DA), we were able to identify critical acylcarnitines that were driving differentiation of our experimental groups for all the tissues studied. While plasma displayed increases in metabolites directly related to mouse VLCAD deficiency (e.g. C16 and C18), organs like the heart, muscle and liver also showed involvement of alternative pathways (e.g. medium chain FAO and ketogenesis), suggesting adaptive measures. Matched correlation analyses showed strong correlations (r > 0.7) between plasma and tissue levels for a small number of metabolites. Overall, our results demonstrate that infection as a stress produces perturbations in metabolism in Acadvl−/− that differ greatly from WT infected and Acadvl−/− pair-fed controls. This model system will be useful for studying the effects of infection on tissue metabolism as well as evaluating interventions aimed at modulating the effects of metabolic decompensation.
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影响因子：
3.8
作者：
Pons, R;Cavadini, P;Taroni, F
通讯作者：
Taroni, F
影响因子：
7.1
作者：
SEATON, TB;WELLE, SL;CAMPBELL, RG
通讯作者：
CAMPBELL, RG
DOI：
10.1016/j.bbadis.2015.08.021
发表时间：
2015-11
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Tarasenko TN;Singh LN;Chatterji-Len M;Zerfas PM;Cusmano-Ozog K;McGuire PJ
通讯作者：
McGuire PJ
DOI：
10.1111/j.1365-2362.2004.01308.x
发表时间：
2004-03-01
影响因子：
5.5
作者：
Spiekerkoetter, U;Tokunaga, C;Strauss, AW
通讯作者：
Strauss, AW
影响因子：
4.2
作者：
Spiekerkoetter, Ute
通讯作者：
Spiekerkoetter, Ute