Abstract
Chronic high-fat diet (HFD) is associated with the onset and progression of hepatic steatosis, and oxidative stress is highly involved in this process. The potential role of sesamol (SEM) against oxidative stress and inflammation at the transcriptional level in a mice model of hepatic steatosis is not known. In this study, we aimed to investigate the scavenging effects of SEM towards reactive oxygen generated by lipid accumulation in the liver of obese mice and to explore the mechanisms of protection. Markers of oxidative stress, vital enzymes involved in stimulating oxidative stress or inflammation, and nuclear transcription of Nrf2 were examined. Our results showed that SEM significantly inhibited the activity of the HFD-induced hepatic enzymes CYP2E1 and NOX2, associated with oxidative stress generation. Additionally, SEM reversed HFD-induced activation of NF-κB, a redox-sensitive transcription factor, and attenuated the expression of hepatic TNF-α, a proinflammatory molecule. Moreover, SEM enhanced HFD-induced hepatic Nrf2 nuclear transcription and increased the levels of its downstream target genes Ho1 and Nqo1, which indicated antiinflammation and antioxidant properties. Our study suggests that chronic HFD led to hepatic steatosis, while SEM exhibited protective effects on the liver by counteracting the oxidative stress and inflammation induced by HFD. The underlying mechanism might involve multiple pathways at the transcriptional level; the antioxidant defense mechanism was in partly mediated by the upregulation of Nrf2.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is considered a global epidemic
Liver weight and body fat were remarkably increased by the high-fat diet (HFD), whereas the values of these two parameters were significantly lower in mice treated with SEM (Figure 1C,D)
We further demonstrated that SEM modulated markers such as MDA and superoxide dismutase (SOD), which are associated with oxidative stress in mice models of hepatic steatosis
Summary
Non-alcoholic fatty liver disease (NAFLD) is considered a global epidemic. 25% of the population) to 100.9 million in 2030 [1] It is one of the most common metabolic disorders that could be caused by abnormal or excessive lipids accumulation, oxidation, or transportation in the liver. The crucial pathobiological aspect of NAFLD is hepatic steatosis that has the tendency to progress to non-alcoholic steatohepatitis (NASH) or even cirrhosis and liver cancer [2,3]. It is well known that several exogenous factors such as a chronic high-fat diet (HFD) or other unhealthy lifestyle habits cause obesity and in parallel influence the onset and progression of hepatic steatosis [4]. Antioxidants and anti-inflammatory factors are crucial for treating hepatic steatosis and slowing the progress of NAFLD
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