C.U.R.E. Centre for Liver Disease Research and Treatment, Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy.
C.U.R.E. Centre for Liver Disease Research and Treatment, Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy.
Free Radic Biol Med. 2013 Dec;65:952-968. doi: 10.1016/j.freeradbiomed.2013.08.174. Epub 2013 Aug 29.
Reactive oxygen species, when released under controlled conditions and limited amounts, contribute to cellular proliferation, senescence, and survival by acting as signaling intermediates. In past decades there has been an epidemic diffusion of nonalcoholic fatty liver disease (NAFLD) that represents the result of the impairment of lipid metabolism, redox imbalance, and insulin resistance in the liver. To date, most studies and reviews have been focused on the molecular mechanisms by which fatty liver progresses to steatohepatitis, but the processes leading toward the development of hepatic steatosis in NAFLD are not fully understood yet. Several nuclear receptors, such as peroxisome proliferator-activated receptors (PPARs) α/γ/δ, PPARγ coactivators 1α and 1β, sterol-regulatory element-binding proteins, AMP-activated protein kinase, liver-X-receptors, and farnesoid-X-receptor, play key roles in the regulation of lipid homeostasis during the pathogenesis of NAFLD. These nuclear receptors may act as redox sensors and may modulate various metabolic pathways in response to specific molecules that act as ligands. It is conceivable that a redox-dependent modulation of lipid metabolism, nuclear receptor-mediated, could cause the development of hepatic steatosis and insulin resistance. Thus, this network may represent a potential therapeutic target for the treatment and prevention of hepatic steatosis and its progression to steatohepatitis. This review summarizes the redox-dependent factors that contribute to metabolism alterations in fatty liver with a focus on the redox control of nuclear receptors in normal liver as well as in NAFLD.
活性氧在受控条件和有限数量下释放时，通过作为信号中间体起作用，有助于细胞增殖、衰老和存活。在过去的几十年中，非酒精性脂肪性肝病（NAFLD）的流行扩散代表了肝脏脂质代谢、氧化还原失衡和胰岛素抵抗受损的结果。迄今为止，大多数研究和综述都集中在脂肪性肝病进展为肝炎的分子机制上，但导致 NAFLD 发生肝脂肪变性的过程尚未完全了解。几种核受体，如过氧化物酶体增殖物激活受体（PPAR）α/γ/δ、PPARγ 共激活物 1α 和 1β、固醇调节元件结合蛋白、AMP 激活蛋白激酶、肝 X 受体和法尼醇 X 受体，在 NAFLD 发病机制中脂质稳态的调节中发挥关键作用。这些核受体可以作为氧化还原传感器，并可以响应作为配体的特定分子来调节各种代谢途径。可以想象，依赖于氧化还原的脂质代谢调节、核受体介导的调节可能导致肝脂肪变性和胰岛素抵抗的发展。因此，该网络可能代表治疗和预防肝脂肪变性及其向肝炎进展的潜在治疗靶点。本综述总结了导致脂肪性肝病代谢改变的氧化还原相关因素，重点介绍了正常肝脏以及 NAFLD 中核受体的氧化还原调控。
