Tricarboxylic acid (TCA) cycle, sphingolipid, and phosphatidylcholine metabolism are dysregulated in T. gondii infection-induced cachexia.
Tricarboxylic acid (TCA) cycle, sphingolipid, and phosphatidylcholine metabolism are dysregulated in T. gondii infection-induced cachexia.
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DOI：
10.1016/j.heliyon.2023.e17411
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发表时间：
2023-07
期刊：
影响因子：
4
通讯作者：
Ewald, Sarah E.
中科院分区：
文献类型：
--
作者：
Feng, Tzu-Yu;Melchor, Stephanie J.;Zhao, Xiao-Yu;Ghumman, Haider;Kester, Mark;Fox, Todd E.;Ewald, Sarah E.
恶病质是一种危及生命的疾病，其特征在于慢性炎性肌肉消耗和全身代谢障碍。尽管恶病质的患病率很高，但目前还没有有效的治疗方法。慢性感染弓形虫的小鼠是一种新的动物模型，它再现了恶病质的慢性动力学。为了了解代谢组织稳态的扰动如何影响循环代谢物的可用性，我们使用质谱分析。尽管循环甘油三酯，非酯化脂肪酸，甘油，鞘脂长链碱和一个子集的磷脂酰胆碱（PC）显着减少，在T。弓形虫感染引起的恶病质。此外，TCA循环中间体α-酮戊二酸、2-羟基戊二酸、琥珀酸、富马酸和苹果酸在恶病质小鼠血清中高度耗竭。鞘脂及其从头合成前体PC是线粒体膜的主要成分，并调节线粒体功能，这与驱动T. gondii引起的慢性恶病质。
Cachexia is a life-threatening disease characterized by chronic, inflammatory muscle wasting and systemic metabolic impairment. Despite its high prevalence, there are no efficacious therapies for cachexia. Mice chronically infected with the protozoan parasite Toxoplasma gondii represent a novel animal model recapitulating the chronic kinetics of cachexia. To understand how perturbations to metabolic tissue homeostasis influence circulating metabolite availability we used mass spectrometry analysis. Despite the significant reduction in circulating triacylglycerides, non-esterified fatty acids, and glycerol, sphingolipid long-chain bases and a subset of phosphatidylcholines (PCs) were significantly increased in the sera of mice with T. gondii infection-induced cachexia. In addition, the TCA cycle intermediates α-ketoglutarate, 2-hydroxyglutarate, succinate, fumarate, and malate were highly depleted in cachectic mouse sera. Sphingolipids and their de novo synthesis precursors PCs are the major components of the mitochondrial membrane and regulate mitochondrial function consistent with a causal relationship in the energy imbalance driving T. gondii-induced chronic cachexia.
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影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
3.7
作者：
Hatter, Jessica A.;Kouche, Yue Moi;Ewald, Sarah E.
通讯作者：
Ewald, Sarah E.
影响因子：
5.5
作者：
Ishay, Yuval;Nachman, Dean;Ilan, Yaron
通讯作者：
Ilan, Yaron
影响因子：
4
作者：
Batista, M. L., Jr.;Neves, R. X.;Seelaender, M.
通讯作者：
Seelaender, M.
影响因子：
4.9
作者：
Cui, Pengfei;Shao, Wei;Lin, Donghai
通讯作者：
Lin, Donghai