Epigenetics in NAFLD/NASH: Targets and therapy

Abstract

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.

Keywords: 3-deazaneplanocin A (PubChem CID: 73087); Berberine (PubChem CID: 2353); DNA methylation; Ezetimibe (PubChem CID: 150311); Gemfibrozil (PubChem CID: 3463); HDAC; Histone modification; Liraglutide (PubChem CID: 16134956); Metformin (PubChem CID: 4091); MicroRNAs; Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; Resveratrol (PubChem CID: 445154); Rimonabant hydrochloride (PubChem CID: 104849); Sitagliptin (PubChem CID: 4369359); Vitamin E (PubChem CID: 14985); Vorinostat (PubChem CID: 5311); β-cryptoxanthin (PubChem CID: 5281235).