Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide. Reactive oxygen species (ROS), as potent oxidants in cells, have been shown to promote the development of NAFLD. Previous studies reported that for ROS-induced cellular oxidative stress, promoting lipid droplet (LD) accumulation is associated with the cellular antioxidation process. However, the regulatory role of LDs in relieving cellular oxidative stress is poorly understood. Here, we showed that Perilipin 5 (PLIN5), a key LD protein related to mitochondria–LD contact, reduced ROS levels and improved mitochondrial function in HepG2 cells. Both mRNA and protein levels of PLIN5 were significantly increased in cells with hydrogen peroxide or lipopolysaccharide (LPS) treatment (p < 0.05). Additionally, the overexpression of PLIN5 promoted LD formation and mitochondria–LD contact, reduced cellular ROS levels and up-regulated mitochondrial function-related genes such as COX and CS. Knockdown PLIN5, meanwhile, showed opposite effects. Furthermore, we identified that cellular oxidative stress up-regulated PLIN5 expression via the JNK-p38-ATF pathway. This study shows that the up-regulation of PLIN5 is a kind of survival strategy for cells in response to stress. PLIN5 can be a potential therapeutic target in NAFLD.
Highlights
There are a large number of patients suffering from non-alcoholic fatty liver disease (NAFLD) all over the world
NAFLD is characterized by the accumulation of lipid droplet (LD) and a raised reactive oxygen species (ROS) level
The results showed that the mRNA level of Perilipin 5 (PLIN5) was up-regulated significantly in hepatic tissues of mice fed with methionine-choline-deficient diet (MCDD) for 4 weeks, 6 weeks, and 8 weeks, and mice fed with high-fat diet (HFD) for 10 weeks, compared to the corresponding control samples
Summary
There are a large number of patients suffering from non-alcoholic fatty liver disease (NAFLD) all over the world. This disease increases the risk of non-alcoholic hepatitis (NASH), chronic interstitial hepatitis, hepatic failure, and even hepatocellular carcinoma [1,2,3]. Some studies have shown that high levels of ROS promote the development of NAFLD/NASH and hepatocellular carcinoma by inducing. There are several antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) responsible for scavenging cellular ROS. The expression levels of SOD and other antioxidant enzymes are decreased in NAFLD/NASH [4]. Lipid droplets (LDs) have been shown to be involved in the cellular stress response process.
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