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非酒精性脂肪性肝炎(NASH)的组织病理学诊断。

Histopathological Diagnosis of Nonalcoholic Steatohepatitis (NASH).

机构信息

Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, VA, USA.

Alliance Pharma Inc, Malvern, PA, USA.

出版信息

Methods Mol Biol. 2022;2455:49-62. doi: 10.1007/978-1-0716-2128-8_5.

DOI:10.1007/978-1-0716-2128-8_5
PMID:35212985
Abstract

Fatty acid beta oxidation (FAO) is a predominant bioenergetic pathway in mammals. Substantial investigations have demonstrated that FAO activity is dysregulated in many pathophysiological conditions including nonalcoholic steatohepatitis (NASH). Convenient and quantitative assays of FAO activities are important for studies of cell metabolism and the biological relevance of FAO to health and diseases. However, most current FAO assays are based on non-physiological culture conditions, measure FAO activity indirectly or lack adequate quantification. We herein describe details of practical protocols for measurement of basal and genetically or pharmacologically regulated FAO activities in the mammalian system. We also discuss the advantages and disadvantages of these assays in the context of experimental purposes.

摘要

脂肪酸β氧化(FAO)是哺乳动物的主要生物能量途径。大量研究表明,FAO 活性在许多病理生理条件下失调,包括非酒精性脂肪性肝炎(NASH)。FAO 活性的方便和定量测定对于细胞代谢以及 FAO 对健康和疾病的生物学相关性的研究非常重要。然而,目前大多数 FAO 测定方法基于非生理培养条件,间接测量 FAO 活性或缺乏充分的定量。本文描述了在哺乳动物系统中测量基础和遗传或药理学调节的 FAO 活性的实用方案的详细信息。我们还讨论了这些测定方法在实验目的方面的优缺点。

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本文引用的文献

1
Functional analysis of molecular and pharmacological modulators of mitochondrial fatty acid oxidation.线粒体脂肪酸氧化的分子和药理学调节剂的功能分析。
Sci Rep. 2020 Jan 29;10(1):1450. doi: 10.1038/s41598-020-58334-7.
2
Inhibition of Mitochondrial Fatty Acid Oxidation Contributes to Development of Nonalcoholic Fatty Liver Disease Induced by Environmental Cadmium Exposure.环境镉暴露诱导非酒精性脂肪肝病的发生与线粒体脂肪酸氧化抑制有关。
Environ Sci Technol. 2019 Dec 3;53(23):13992-14000. doi: 10.1021/acs.est.9b05131. Epub 2019 Nov 14.
3
Quiescent Endothelial Cells Upregulate Fatty Acid β-Oxidation for Vasculoprotection via Redox Homeostasis.
静息内皮细胞通过氧化还原稳态上调脂肪酸β氧化以实现血管保护。
Cell Metab. 2018 Dec 4;28(6):881-894.e13. doi: 10.1016/j.cmet.2018.07.016. Epub 2018 Aug 23.
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Fatty acid oxidation: An emerging facet of metabolic transformation in cancer.脂肪酸氧化:癌症代谢转化中的一个新兴方面。
Cancer Lett. 2018 Oct 28;435:92-100. doi: 10.1016/j.canlet.2018.08.006. Epub 2018 Aug 10.
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Etomoxir Inhibits Macrophage Polarization by Disrupting CoA Homeostasis.依他莫司抑制巨噬细胞极化作用是通过破坏辅酶 A 稳态实现的。
Cell Metab. 2018 Sep 4;28(3):490-503.e7. doi: 10.1016/j.cmet.2018.06.001. Epub 2018 Jun 28.
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Identifying off-target effects of etomoxir reveals that carnitine palmitoyltransferase I is essential for cancer cell proliferation independent of β-oxidation.鉴定依泽替米贝的脱靶效应表明,肉毒碱棕榈酰基转移酶 I 对于癌细胞增殖是必需的,而不依赖于β-氧化。
PLoS Biol. 2018 Mar 29;16(3):e2003782. doi: 10.1371/journal.pbio.2003782. eCollection 2018 Mar.
7
JAK/STAT3-Regulated Fatty Acid β-Oxidation Is Critical for Breast Cancer Stem Cell Self-Renewal and Chemoresistance.JAK/STAT3 调控的脂肪酸 β-氧化对乳腺癌干细胞自我更新和化疗耐药至关重要。
Cell Metab. 2018 Jan 9;27(1):136-150.e5. doi: 10.1016/j.cmet.2017.11.001. Epub 2017 Dec 14.
8
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Inhibition of fatty acid oxidation as a therapy for MYC-overexpressing triple-negative breast cancer.抑制脂肪酸氧化作为治疗MYC过表达三阴性乳腺癌的一种方法。
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