Valdecoxib attenuates lipid-induced hepatic steatosis through autophagy-mediated suppression of endoplasmic reticulum stress

This study investigated the effects of VAL on lipid accumulation and lipogenesis in human primary hepatocytes. Treatment with VAL suppressed lipid accumulation and expressions of lipogenic genes, such as processed sterol regulatory element binding proteins (SREBP1) and stearoyl-CoA desaturase-1 (SCD1) in palmitate-treated hepatocytes. Furthermore, VAL ameliorated dose-dependently palmitate-induced ER stress markers. Treatment of hepatocytes with VAL increased AMPK phosphorylation and SIRT6 expression. siRNA-mediated suppression of AMPK or SIRT6 abolished the effects of VAL on lipid accumulation, lipogenesis, and endoplasmic reticulum (ER) stress in palmitate-treated hepatocytes. Administration of VAL ameliorated hepatic lipid accumulation and lipogenic protein expression in HFD-fed mice. Moreover, in vivo AMPK siRNA transfection abolished the effects of VAL on hepatic steatosis and lipid metabolism. These results suggest that VAL suppresses ER stress through the AMPK/SIRT6 pathway, thereby attenuating hepatic steatosis under hyperlipidemic conditions. Using VAL, the current study results provide clues for developing a novel therapeutic agent for treating non-alcoholic fatty liver disease.PMID:35358477 | DOI:10.1016/j.bcp.2022.115022
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Source Type: research