<p class="first" id="d3248499e109">Nonalcoholic fatty liver disease (NAFLD) has emerged
as the most common chronic liver
disease worldwide and is strongly associated with the presence of oxidative stress.
Disturbances in lipid metabolism lead to hepatic lipid accumulation, which affects
different reactive oxygen species (ROS) generators, including mitochondria, endoplasmic
reticulum, and NADPH oxidase. Mitochondrial function adapts to NAFLD mainly through
the downregulation of the electron transport chain (ETC) and the preserved or enhanced
capacity of mitochondrial fatty acid oxidation, which stimulates ROS overproduction
within different ETC components upstream of cytochrome c oxidase. However, non-ETC
sources of ROS, in particular, fatty acid β-oxidation, appear to produce more ROS
in hepatic metabolic diseases. Endoplasmic reticulum stress and NADPH oxidase alterations
are also associated with NAFLD, but the degree of their contribution to oxidative
stress in NAFLD remains unclear. Increased ROS generation induces changes in insulin
sensitivity and in the expression and activity of key enzymes involved in lipid metabolism.
Moreover, the interaction between redox signaling and innate immune signaling forms
a complex network that regulates inflammatory responses. Based on the mechanistic
view described above, this review summarizes the mechanisms that may account for the
excessive production of ROS, the potential mechanistic roles of ROS that drive NAFLD
progression, and therapeutic interventions that are related to oxidative stress.
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