Mitochondria Matter: Systemic Aspects of Nonalcoholic Fatty Liver Disease (NAFLD) and Diagnostic Assessment of Liver Function by Stable Isotope Dynamic Breath Tests.
Mitochondria Matter: Systemic Aspects of Nonalcoholic Fatty Liver Disease (NAFLD) and Diagnostic Assessment of Liver Function by Stable Isotope Dynamic Breath Tests.
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DOI：
10.3390/ijms22147702
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发表时间：
2021-07-19
影响因子：
5.6
通讯作者：
Portincasa P
中科院分区：
文献类型：
--
作者：
Di Ciaula A;Calamita G;Shanmugam H;Khalil M;Bonfrate L;Wang DQ;Baffy G;Portincasa P
肝脏在全身代谢过程中起着关键作用，包括碳水化合物、脂质和蛋白质的解毒、合成、储存和输出。全球范围内肥胖和代谢紊乱的上升趋势通常与非酒精性脂肪性肝病（NAFLD）有关，NAFLD已成为最常见的慢性肝病类型，具有进展为肝硬化和肝细胞癌的风险。肝线粒体在降解碳水化合物、蛋白质、脂质和外源性物质的途径中起关键作用，并为体细胞提供能量。线粒体的形态和功能完整性保证了游离脂肪酸的β-氧化和三羧酸循环的正常功能。临床医学中对NAFLD患者肝脏的评估需要准确，包括病史、体格检查、影像学和实验室检测。现在可以通过新的诊断工具来评估慢性肝病和NAFLD中的线粒体功能。“动态”肝功能测试包括基于使用标记有非放射性、天然存在的稳定同位素13 C的底物的呼吸测试（BT）。底物的肝细胞代谢将产生13 CO2，其在呼吸中排出并通过质谱或红外光谱测量。呼吸中的13 CO2水平是肝细胞胞质溶胶、微粒体和线粒体中发生的特定代谢过程的生物标志物。13 C-BT探索不同的慢性肝病，包括单纯性肝脂肪变性、非酒精性脂肪性肝炎、肝纤维化、肝硬化、肝细胞癌、药物和酒精影响。在NAFLD中，13 C-BT使用底物如α-酮异己酸、甲硫氨酸和辛酸来评估线粒体氧化能力，该能力可能在疾病早期受损。13 C-BT是一种间接、经济、简便的评价动态肝功能的方法。预期在临床医学中有进一步的应用。在这篇综述中，我们讨论了肝脏线粒体在NAFLD进展中的参与，以及13 C-BT在评估线粒体功能中的作用及其在预防和管理NAFLD中的潜在用途。
The liver plays a key role in systemic metabolic processes, which include detoxification, synthesis, storage, and export of carbohydrates, lipids, and proteins. The raising trends of obesity and metabolic disorders worldwide is often associated with the nonalcoholic fatty liver disease (NAFLD), which has become the most frequent type of chronic liver disorder with risk of progression to cirrhosis and hepatocellular carcinoma. Liver mitochondria play a key role in degrading the pathways of carbohydrates, proteins, lipids, and xenobiotics, and to provide energy for the body cells. The morphological and functional integrity of mitochondria guarantee the proper functioning of β-oxidation of free fatty acids and of the tricarboxylic acid cycle. Evaluation of the liver in clinical medicine needs to be accurate in NAFLD patients and includes history, physical exam, imaging, and laboratory assays. Evaluation of mitochondrial function in chronic liver disease and NAFLD is now possible by novel diagnostic tools. “Dynamic” liver function tests include the breath test (BT) based on the use of substrates marked with the non-radioactive, naturally occurring stable isotope 13C. Hepatocellular metabolization of the substrate will generate 13CO2, which is excreted in breath and measured by mass spectrometry or infrared spectroscopy. Breath levels of 13CO2 are biomarkers of specific metabolic processes occurring in the hepatocyte cytosol, microsomes, and mitochondria. 13C-BTs explore distinct chronic liver diseases including simple liver steatosis, non-alcoholic steatohepatitis, liver fibrosis, cirrhosis, hepatocellular carcinoma, drug, and alcohol effects. In NAFLD, 13C-BT use substrates such as α-ketoisocaproic acid, methionine, and octanoic acid to assess mitochondrial oxidation capacity which can be impaired at an early stage of disease. 13C-BTs represent an indirect, cost-effective, and easy method to evaluate dynamic liver function. Further applications are expected in clinical medicine. In this review, we discuss the involvement of liver mitochondria in the progression of NAFLD, together with the role of 13C-BT in assessing mitochondrial function and its potential use in the prevention and management of NAFLD.
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影响因子：
7.6
作者：
Banasch, M.;Emminghaus, R.;Goetze, O.
通讯作者：
Goetze, O.
影响因子：
16.6
作者：
An, Ping;Wei, Lin-Lin;Popov, Yury, V
通讯作者：
Popov, Yury, V
DOI：
10.1097/meg.0000000000000374
发表时间：
2015-07-01
影响因子：
2.1
作者：
Bonfrate, Leonilde;Krawczyk, Marcin;Portincasa, Piero
通讯作者：
Portincasa, Piero
影响因子：
4.2
作者：
Banasch M;Ellrichmann M;Tannapfel A;Schmidt WE;Goetze O
通讯作者：
Goetze O
影响因子：
30.8
作者：
Buch, Stephan;Stickel, Felix;Hampe, Jochen
通讯作者：
Hampe, Jochen