Melatonin induces Nrf2‐HO‐1 reprogramming and corrections in hepatic core clock oscillations in Non‐alcoholic fatty liver disease

Melatonin pleiotropically regulates physiological events and has a putative regulatory role in the circadian clock desynchrony-mediated Non-alcoholic fatty liver disease (NAFLD). In this study, we investigated perturbations hepatic gene, Nrf2-HO-1 oscillations conditions of high-fat high fructose (HFHF) diet and/or jet lag (JL)-mediated NAFLD. treatment (100 µM) to HepG2 cells led an improvement oscillatory pattern genes (Clock, Bmal1, Per) oleic acid (OA)-induced desynchrony, while Cry, Nrf2, HO-1 remain oblivious melatonin that was also validated by circwave analysis. C57BL/6J mice subjected HFHF JL, treated with showed profile lipid (CPT-1, PPARa, SREBP-1c), function (AST ALT) histomorphology liver. A detailed scrutiny revealed mRNA protein profiles Bmal1 (at ZT6) Clock ZT12) underwent corrective changes oscillations, but moderate corrections were recorded other components (Per1, Per2, Cry2). induced anti-oxidant (Nrf2, HO-1, Keap1) subtly contributed overall NAFLD herein. Taken together, reprograming core leads HFHF/JL-induced