Dehydrocostus lactone ameliorates lipid accumulation, insulin resistance, and endoplasmic reticulum stress in palmitate-treated hepatocytes

Abstract

Abstract Fatty liver disease is caused by lipid accumulation in the liver, insulin resistance (IR), reactive oxygen species (ROS), and endoplasmic reticulum (ER) stress. Dehydrocostus lactone (DHE) has anticancer, anti-inflammatory, and anti-ulcer effects. However, its effects on hepatic steatosis and IR remain unclear. In this study, we investigated whether DHE has antisteatotic effect on fatty liver in vitro. Hepatocytes HepG2 and SNU-449 cells were exposed to 0.25 mM palmitate (PA), and then antisteatotic effect was evaluated by treatment with 10 μM DHE. DHE treatment reduced lipid accumulation and lipogenesis factor protein levels, compared with PA-treated hepatocytes. DHE treatment also decreased gluconeogenesis marker expression and recovered IR in PA-treated hepatocytes, and promoted glucose uptake in PA-treated HepG2 cells. Additionally, the levels of ROS and ER stress factors in PA-treated HepG2 cells were reduced by DHE treatment, compared with PA-treated HepG2 cells. Overall, DHE decreased lipid accumulation and lipogenesis factors as well as recovered IR, gluconeogenesis, and glucose uptake by reducing ER stress and ROS levels in PA-treated hepatocytes. Thus, DHE is a potential antisteatotic agent.

Keywords

• Dehydrocostus lactone
• Hepatocytes
• Lipid accumulation
• Insulin resistance
• Endoplasmic reticulum stress
• Reactive oxidative species