Punicalagin Attenuates Palmitate-Induced Lipid Droplet Content by Simultaneously Improving Autophagy in Hepatocytes.

SCOPE Several studies showed that excessive lipid intake can cause hepatic steatosis. To investigate lipotoxicity on cellular level, palmitate (PA) is often used to highly increase lipid droplets (LDs). One way to remove LDs is autophagy, while it is controversially discussed if autophagy is also affected by PA. We aimed to investigate whether PA-induced LD accumulation can impair autophagy and punicalagin, a natural autophagy inducer from pomegranate, can improve it. METHODS AND RESULTS To verify the role of autophagy in LD degradation, HepG2 cells were treated with PA and analyzed for LD and perilipin 2 content in presence of autophagy inducer Torin 1 and inhibitor 3-Methyladenine. PA alone seems to initially induce autophagy-related proteins but impairs autophagic-flux in a time-dependent manner, considering 6h and 24h PA. To examine whether punicalagin can prevent autophagy impairment, we cotreated cells 24h with PA and punicalagin. Results showed that punicalagin preserves expression of autophagy-related proteins and autophagic flux, while simultaneously decreasing LDs and perilipin 2. CONCLUSION Data provide new insights into the role of PA-induced excessive LD content on autophagy and suggest autophagy-inducing properties of punicalagin, indicating that punicalagin could be a health-beneficial compound for future research on lipotoxicity in liver. This article is protected by copyright. All rights reserved.