Abstract
The progress of the hepatic steatosis (HS), a clinicopathological status, is influenced by cellular oxidative stress, lipogenesis, fatty acid (FA) oxidation, and inflammatory responses. Because antioxidants are gaining attention as potent preventive agents for HS, we aimed to investigate anti-lipogenic effects of the antioxidants vitamin C (VC), N-acetylcysteine (NAC), and astaxanthin (ATX) using hepatocytes. For this, we established an in vitro model using 1 mM oleic acid (OA) and human liver hepatocellular carcinoma (HepG2) cells; 10 μM antioxidants were evaluated for their ability to reduce fat accumulation in hepatocytes. Our results showed that all three antioxidants were effective to reduce fat accumulation for the molecular targets such as reduction in lipid droplets, triglyceride (TG) concentration, reactive oxygen species (ROS) production, and cell apoptosis, as well as in gene expressions of endoplasmic reticulum (ER) stress-related effectors, lipogenesis, and inflammatory cytokines. There were simultaneous increases in diphenyl-1-picrylhydrazyl (DPPH) radical scavenging effect, cell survival, AMPK phosphorylation, NRF2-related gene expression for cellular defense, and FA β-oxidation. However, among these, ATX more effectively inhibited ER stress and lipogenesis at the intracellular level than VC or NAC. Consequently, ATX was also more effective in inhibiting cell death, lipotoxicity, and inflammation. Our result emphasizes that ATX achieved greater lipotoxicity reduction than VC and NAC.
Highlights
Metabolic syndrome (MS) is defined by the presence of metabolic alterations that increase an individual’s risk of developing type 2 diabetes mellitus (T2DM) and cardiovascular disease [1,2]
Cholesterol and fatty acid (FA) are accumulated in the liver of patients with nonalcoholic fatty liver disease (NAFLD) through this mechanism; this is accompanied by oxidative stress and reactive oxygen species (ROS) formation [9]
To establish an in vitro model of hepatic cellular steatosis, HepG2 cells were treated with oleic acid (OA) solutions of various concentrations (0.5, 1.0, 1.5, and 2 mM)
Summary
Metabolic syndrome (MS) is defined by the presence of metabolic alterations that increase an individual’s risk of developing type 2 diabetes mellitus (T2DM) and cardiovascular disease [1,2]. ATX, a natural antioxidant carotenoid occurring in several living organisms, has a positive effect on cardiovascular disease, obesity, and dyslipidemia as a quencher of ROS/RNS single- and 2-electron oxidants and a chain-breaking scavenger of free radicals [12]. Each of these natural and synthetic compounds, VC, NAC, and ATX, has been tested for protective effects on HS and NAFLD; they have never been simultaneously compared
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