Abstract
Non-alcoholic fatty liver disease (NAFLD) is a common disease in Western nations and ranges in severity from steatosis to steatohepatitis (NASH). NAFLD is a genetic-environmental-metabolic stress-related disease of unclear pathogenesis. NAFLD is triggered by caloric overconsumption and physical inactivity, which lead to insulin resistance and oxidative stress. A growing body of evidence indicates that mitochondrial dysfunction plays a critical role in the pathogenesis of NAFLD. Mitochondrial dysfunction not only promotes fat accumulation, but also leads to generation of reactive oxygen species (ROS) and lipid peroxidation, resulting in oxidative stress in hepatocytes. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important modulator of antioxidant signaling that serves as a primary cellular defense against the cytotoxic effects of oxidative stress. The pharmacological induction of Nrf2 ameliorates obesity-associated insulin resistance and NAFLD in a mouse model. Sulforaphane and its precursor glucoraphanin are derived from broccoli sprouts and are the most potent natural Nrf2 inducers—they may protect mitochondrial function, thus suppressing the development of NASH. In this review, we briefly describe the role of mitochondrial dysfunction in the pathogenesis of NASH and the effects of glucoraphanin on its development.
Highlights
Non-alcoholic fatty liver disease (NAFLD) ranges from simple hepatic steatosis and nonalcoholic steatohepatitis (NASH) to cirrhosis [1,2]
This implies that strategies for suppressing M1 macrophage polarization and/or enhancing M2 macrophage polarization may protect against chronic inflammation and insulin resistance, and thereby attenuate the progression of NASH
Oxidative stress due to reactive oxygen species (ROS) plays a key role in the development of insulin resistance and NASH
Summary
Non-alcoholic fatty liver disease (NAFLD) ranges from simple hepatic steatosis and nonalcoholic steatohepatitis (NASH) to cirrhosis [1,2]. NAFLD is a risk factor for many metabolic syndromes—including insulin resistance, type 2 diabetes, and cardiovascular disease—the development of which results in increased morbidity and mortality [2,10]. NAFLD is caused by factors other than alcohol and other damaging agents, such as hepatitis C, medications, parenteral nutrition, Wilson’s disease, and severe malnutrition [11], and is diagnosed when hepatic fat accumulation in the form of triglycerides (TG) exceeds 5% of the total liver weight [12]. The multiple-hit-hypothesis suggests that other factors, including adipokines and mitochondrial dysfunction, contribute to the development of NAFLD (Figure 1) [15,16]. Here we describe the role of mitochondria in the progression of NASH and the beneficial effect of glucoraphanin on its progression, which is mediated by improvement of mitochondrial dysfunction
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