Associations between fatty acid oxidation, hepatic mitochondrial function, and plasma acylcarnitine levels in mice.
Associations between fatty acid oxidation, hepatic mitochondrial function, and plasma acylcarnitine levels in mice.
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DOI：
10.1186/s12986-018-0241-7
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发表时间：
2018
影响因子：
4.5
通讯作者：
Berge RK
中科院分区：
文献类型：
--
作者：
Bjørndal B;Alterås EK;Lindquist C;Svardal A;Skorve J;Berge RK
已知4 - 硫代脂肪酸十四烷基硫代丙酸（TTP）可抑制线粒体β - 氧化，并且可在啮齿动物中用作化学诱导的肝脂肪变性模型，而3 - 硫代脂肪酸十四烷基硫代乙酸（TTA）通过激活过氧化物酶体增殖物激活受体α（PPARα）刺激脂肪酸氧化。我们希望确定这两种化合物如何影响体内呼吸和线粒体效率，另外一个目的是阐明线粒体功能是否反映在血浆酰基肉碱水平上。
将C57BL / 6小鼠分为4组，每组10只，分别喂食对照低脂饮食、含0.4%（w / w）TTP的低脂饮食、含0.4% TTA的低脂饮食或这两种脂肪酸的组合，持续三周（n = 10）。处死后，在新鲜肝脏样本中分析β - 氧化和氧化磷酸化（OXPHOS）能力。使用透射电子显微镜研究肝线粒体。测量血浆、心脏和肝脏中的脂质类别，测量血浆中的酰基肉碱，并测量肝脏中的基因表达。
TTP饮食导致肝脏脂质蓄积，血浆L - 肉碱和乙酰肉碱耗竭，以及棕榈酰肉碱和非酯化脂肪酸水平升高。在心脏中未观察到明显的脂质蓄积。TTA补充剂导致肝脏β - 氧化增强，同时伴有血浆中乙酰肉碱和棕榈酰肉碱水平升高。对线粒体呼吸的分析表明，TTP降低了氧化磷酸化，而TTA增加了电子传递系统的最大呼吸能力。TTP和TTA联合处理导致参与PPAR反应和L - 肉碱代谢的基因受到强烈刺激，并部分阻止了肝脏中三酰甘油的蓄积，同时伴有过氧化物酶体β - 氧化增加和血浆乙酰肉碱耗竭。尽管喂食TTA + TTP的小鼠肝脏中线粒体数量增加，但OXPHOS能力显著降低。
这项研究表明，脂肪酸β - 氧化直接影响肝脏中的线粒体呼吸能力。由于血浆酰基肉碱反映了喂食TTP的小鼠中线粒体β - 氧化的降低，它们可能是监测线粒体功能的有用工具。由于线粒体功能障碍是代谢性疾病的一个主要决定因素，这支持将它们用作人类心血管风险的血浆标志物。然而，结果表明，高PPAR激活会使血浆酰基肉碱水平的解读变得复杂。
本文的在线版本（10.1186 / s12986 - 018 - 0241 - 7）包含补充材料，授权用户可获取。
The 4-thia fatty acid tetradecylthiopropionic acid (TTP) is known to inhibit mitochondrial β-oxidation, and can be used as chemically induced hepatic steatosis-model in rodents, while 3-thia fatty acid tetradecylthioacetic acid (TTA) stimulates fatty acid oxidation through activation of peroxisome proliferator activated receptor alpha (PPARα). We wished to determine how these two compounds affected in vivo respiration and mitochondrial efficiency, with an additional goal to elucidate whether mitochondrial function is reflected in plasma acylcarnitine levels. C57BL/6 mice were divided in 4 groups of 10 mice and fed a control low-fat diet, low-fat diets with 0.4% (w/w) TTP, 0.4% TTA or a combination of these two fatty acids for three weeks (n = 10). At sacrifice, β-oxidation and oxidative phosphorylation (OXPHOS) capacity was analysed in fresh liver samples. Hepatic mitochondria were studied using transmission electron microscopy. Lipid classes were measured in plasma, heart and liver, acylcarnitines were measured in plasma, and gene expression was measured in liver. The TTP diet resulted in hepatic lipid accumulation, plasma L-carnitine and acetylcarnitine depletion and elevated palmitoylcarnitine and non-esterified fatty acid levels. No significant lipid accumulation was observed in heart. The TTA supplement resulted in enhanced hepatic β-oxidation, accompanied by an increased level of acetylcarnitine and palmitoylcarnitine in plasma. Analysis of mitochondrial respiration showed that TTP reduced oxidative phosphorylation, while TTA increased the maximum respiratory capacity of the electron transport system. Combined treatment with TTP and TTA resulted in a profound stimulation of genes involved in the PPAR-response and L-carnitine metabolism, and partly prevented triacylglycerol accumulation in the liver concomitant with increased peroxisomal β-oxidation and depletion of plasma acetylcarnitines. Despite an increased number of mitochondria in the liver of TTA + TTP fed mice, the OXPHOS capacity was significantly reduced. This study indicates that fatty acid β-oxidation directly affects mitochondrial respiratory capacity in liver. As plasma acylcarnitines reflected the reduced mitochondrial β-oxidation in TTP-fed mice, they could be useful tools to monitor mitochondrial function. As mitochondrial dysfunction is a major determinant of metabolic disease, this supports their use as plasma markers of cardiovascular risk in humans. Results however indicate that high PPAR activation obscures the interpretation of plasma acylcarnitine levels. The online version of this article (10.1186/s12986-018-0241-7) contains supplementary material, which is available to authorized users.
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四烷基噻吩丙酸诱导肝线粒体功能障碍和脂肪变性，并伴有小鼠血浆同型半胱氨酸的增加。
影响因子：
4.5
作者：
Berge RK;Bjørndal B;Strand E;Bohov P;Lindquist C;Nordrehaug JE;Svardal A;Skorve J;Nygård O
通讯作者：
Nygård O
影响因子：
3.7
作者：
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通讯作者：
Berge, Rolf Kristian
影响因子：
2.8
作者：
Mavrogiannaki AN;Migdalis IN
通讯作者：
Migdalis IN
DOI：
10.1016/j.plefa.2010.02.012
发表时间：
2010-04-01
影响因子：
3
作者：
Byrne, Christopher D.
通讯作者：
Byrne, Christopher D.
影响因子：
16.2
作者：
Mihalik SJ;Michaliszyn SF;de las Heras J;Bacha F;Lee S;Chace DH;DeJesus VR;Vockley J;Arslanian SA
通讯作者：
Arslanian SA