缺氧和脂肪肝

Hypoxia and fatty liver

 



摘要
肝脏是一个中枢器官,代谢过剩的营养,以糖原和脂质的形式储存,并向外周组织提供能产生能量的基质,以维持其功能,即使在饥饿的条件下也是如此。这些过程需要相当多的氧气,这导致肝小叶中氧梯度陡增。酒精的摄入和/或过量的食物摄入会大大改变肝脏的代谢平衡,从而导致脂肪肝。脂肪肝是全世界慢性肝病的主要病因,从单纯性脂肪变性,到脂肪肝和肝纤维化,再到肝硬化。脂肪肝的肝代谢和组织重构的改变进一步破坏肝氧平衡,导致严重的肝缺氧。

 

作为适应低氧应激反应的主要调节者,低氧诱导因子(HIFs)通过在胎儿发育期间以及在癌症、心力衰竭和糖尿病等多种疾病条件下激活靶基因,调节各种细胞和器官功能,包括红细胞生成、血管生成、代谢需求和细胞存活。在过去的十年里,HIFs作为调节脂质代谢和脂肪肝形成的关键因素已经很明显。

 

本文综述了缺氧和HIFs在脂肪肝发生和发展过程中调控脂质代谢的分子机制。


关键词:缺氧,脂肪肝,缺氧诱导因子,脂质代谢,阻塞性睡眠呼吸暂停


核心提示:缺氧发生在脂肪肝的发展和发展过程中。最近的报道揭示了缺氧诱导因子(HIFs)的病理意义,HIFs是缺氧反应的主要调控因子,在环境和异构体依赖方式下调控脂质代谢。在这篇综述中,我们总结了最近关于HIFs依赖性调节在脂肪肝中的各种作用的发现。


缺氧和脂肪肝https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223242/

Hypoxia and fatty liver


Tomohiro Suzuki, Satoko Shinjo, Takatomo Arai, Mai Kanai, and Nobuhito Goda
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Abstract
The liver is a central organ that metabolizes excessive nutrients for storage in the form of glycogen and lipids and supplies energy-producing substrates to the peripheral tissues to maintain their function, even under starved conditions. These processes require a considerable amount of oxygen, which causes a steep oxygen gradient throughout the hepatic lobules. Alcohol consumption and/or excessive food intake can alter the hepatic metabolic balance drastically, which can precipitate fatty liver disease, a major cause of chronic liver diseases worldwide, ranging from simple steatosis, through steatohepatitis and hepatic fibrosis, to liver cirrhosis. Altered hepatic metabolism and tissue remodeling in fatty liver disease further disrupt hepatic oxygen homeostasis, resulting in severe liver hypoxia. As master regulators of adaptive responses to hypoxic stress, hypoxia-inducible factors (HIFs) modulate various cellular and organ functions, including erythropoiesis, angiogenesis, metabolic demand, and cell survival, by activating their target genes during fetal development and also in many disease conditions such as cancer, heart failure, and diabetes. In the past decade, it has become clear that HIFs serve as key factors in the regulation of lipid metabolism and fatty liver formation. This review discusses the molecular mechanisms by which hypoxia and HIFs regulate lipid metabolism in the development and progression of fatty liver disease.

Keywords: Hypoxia, Fatty liver disease, Hypoxia-inducible factor, Lipid metabolism, Obstructive sleep apnea


Core tip: Hypoxia occurs in the development and progression of fatty liver disease. Recent reports have shed light on the pathological significance of hypoxia inducible factors (HIFs), master regulators of the hypoxic response, with regard to their regulation of lipid metabolism in context- and isoform-dependent manners. In this review, we summarize recent findings on the various roles of HIF-dependent regulation in fatty liver disease.
Hypoxia and fatty liver https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223242

https://www.sciencedirect.com/science/article/pii/S0168827811003862