Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India.
Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research, Hajipur 844102, Bihar, India.
Pharmacol Res. 2021 May;167:105484. doi: 10.1016/j.phrs.2021.105484. Epub 2021 Mar 24.
Recently non-alcoholic fatty liver disease (NAFLD) has grabbed considerable scientific attention, owing to its rapid increase in prevalence worldwide and growing burden on end-stage liver diseases. Metabolic syndrome including obesity, diabetes, and hypertension poses a grave risk to NAFLD etiology and progression. With no drugs available, the mainstay of NAFLD management remains lifestyle changes with exercise and dietary modifications. Nonselective drugs such as metformin, thiazolidinediones (TZDs), ursodeoxycholic acid (UDCA), silymarin, etc., are also being used to target the interrelated pathways for treating NAFLD. Considering the enormous disease burden and the unmet need for drugs, fresh insights into pathogenesis and drug discovery are required. The emergence of the field of epigenetics offers a convincing explanation for the basis of lifestyle, environmental, and other risk factors to influence NAFLD pathogenesis. Therefore, understanding these epigenetic modifications to target the primary cause of the disease might prove a rational strategy to prevent the disease and develop novel therapeutic interventions. Apart from describing the role of epigenetics in the pathogenesis of NAFLD as in other reviews, this review additionally provides an elaborate discussion on exploiting the high plasticity of epigenetic modifications in response to environmental cues, for developing novel therapeutics for NAFLD. Besides, this extensive review provides evidence for epigenetic mechanisms utilized by several potential drugs for NAFLD.
最近，非酒精性脂肪性肝病（NAFLD）引起了相当多的科学关注，因为它在全球范围内的患病率迅速增加，并且对终末期肝病的负担越来越大。包括肥胖、糖尿病和高血压在内的代谢综合征对 NAFLD 的病因学和进展构成了严重威胁。由于没有可用的药物，NAFLD 的主要治疗方法仍然是通过运动和饮食改变来改变生活方式。二甲双胍、噻唑烷二酮类（TZDs）、熊去氧胆酸（UDCA）、水飞蓟素等非选择性药物也被用于针对 NAFLD 的相关途径进行治疗。鉴于疾病负担巨大且对药物的需求未得到满足，需要对发病机制和药物发现有新的认识。表观遗传学领域的出现为生活方式、环境和其他风险因素影响 NAFLD 发病机制的基础提供了令人信服的解释。因此，了解针对疾病主要病因的这些表观遗传修饰可能是预防疾病和开发新的治疗干预措施的合理策略。除了在其他综述中描述表观遗传学在 NAFLD 发病机制中的作用外，本综述还详细讨论了利用表观遗传修饰对环境线索的高度可塑性来开发治疗 NAFLD 的新疗法。此外，这篇广泛的综述为几种潜在的用于治疗 NAFLD 的药物所利用的表观遗传机制提供了证据。
