Steatotic liver diseases (SLDs) affect one-third of the population, but the pathogenesis underlying these diseases is not well understood, limiting the available treatments. A common factor in SLDs is increased hepatic mitochondrial reductive stress, which occurs as a result of excessive lipid and alcohol metabolism. Recent research has also shown that genetic risk factors contribute to this stress. This review aims to explore how these risk factors increase hepatic mitochondrial reductive stress and how it disrupts hepatic metabolism, leading to SLDs. Additionally, the review will discuss the latest clinical studies on pharmaceutical treatments for SLDs, specifically peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists, thyroid hormone receptor (THR) agonists, acetyl-CoA carboxylase (ACC) inhibitors, and mitochondrial uncouplers. These treatments have a common effect of decreasing hepatic mitochondrial reductive stress, which has been largely overlooked.

脂肪肝病 (SLD) 影响着三分之一的人口，但这些疾病的发病机制尚不清楚，限制了可用的治疗方法。 SLD 的一个常见因素是肝脏线粒体还原应激增加，这是脂质和酒精代谢过度的结果。最近的研究还表明，遗传风险因素会导致这种压力。本综述旨在探讨这些危险因素如何增加肝脏线粒体还原应激，以及如何扰乱肝脏代谢，导致 SLD。此外，该综述还将讨论 SLD 药物治疗的最新临床研究，特别是过氧化物酶体增殖物激活受体 γ (PPAR-γ) 激动剂、甲状腺激素受体 (THR) 激动剂、乙酰辅酶 A 羧化酶 (ACC) 抑制剂和线粒体解偶联剂。这些治疗的共同作用是减少肝线粒体还原应激，但这一点在很大程度上被忽视了。