Ursodeoxycholic acid alleviates nonalcoholic fatty liver disease by inhibiting apoptosis and improving autophagy via activating AMPK

• DOI: 10.1016/j.bbrc.2020.05.128
• Publication Date: 2020-06-25T21:03:45Z
• Authors: Pengbo Wu; Jinbo Zhao; Yitian Guo; Yuanjie Yu; Xiaoman Wu; Hongmiao Xiao
• Keywords: Enzyme Activation; Male; Rats, Sprague-Dawley; 0301 basic medicine; 03 medical and health sciences; Non-alcoholic Fatty Liver Disease; Ursodeoxycholic Acid; Autophagy; Animals; Enzyme Activators; Apoptosis; AMP-Activated Protein Kinases

Ursodeoxycholic acid (UDCA), first identified in bear bile, was widely used in cholestatic liver diseases. Our previous studies have suggested UDCA may exert favorable influence on hepatic steatosis. However, the molecular mechanism remains elusive. Given the role of autophagy and apoptosis dysregulation in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and pharmacological effects of UDCA on modulating autophagy, apoptosis. we sought to investigate whether UDCA had therapeutic effect on NAFLD and its mechanism of modulating autophagy, apoptosis. Our finding revealed that UDCA exerted obviously favorable influence on hepatic steatosis in NAFLD rats by activating AMP-activated protein kinase (AMPK). Mechanistic studies indicated UDCA inhibited apoptosis and improved autophagy by influencing Bcl-2/Beclin-1 and Bcl-2/Bax complex interaction. Importantly, above-mentioned influence of UDCA on autophagy, apoptosis and Bcl-2/Beclin-1, Bcl-2/Bax complex interaction in NAFLD were partly counteracted by AMPK inhibitor compound C(CC). In conclusion, UDCA exerts favorable influence on hepatic steatosis in NAFLD rats, which is attributable to apoptosis inhibition and autophagy induction by influencing Bcl-2/Beclin-1 complex and Bcl-2/Bax complex interaction via activating AMPK, indicating that UDCA may be a promising therapeutic target for NAFLD.