Antioxid Redox Signal. 2019 Jun 28.
SIGNIFICANCE: Highly prevalent in Western cultures, obesity, metabolic syndrome, and diabetes increase the risk of cardiovascular morbidity and mortality and cost health care systems billions of dollars annually. At the cellular level, obesity, metabolic syndrome, and diabetes are associated with increased production of reactive oxygen species (ROS). Increased levels of ROS production in key organ systems like adipose tissue, skeletal muscle, and the vasculature causes disruption of tissue homeostasis leading to increased morbidity and risk of mortality. More specifically, growing evidence implicates the NADPH oxidase (Nox) enzymes in these pathologies through impairment of insulin signaling, inflammation, and vascular dysfunction. The Nox family of enzymes is a major driver of redox signaling through its production of superoxide anion, hydrogen peroxide and downstream oxidative metabolites.
CRITICAL ISSUES: However, due to the short half-lives of individual ROS and/or cellular defense systems, radii of ROS diffusion are commonly short, restricting redox signaling and oxidant stress to often localized events. Thus, special emphasis should be placed on cell type and subcellular location of Nox enzymes to better understand their role in the pathophysiology of metabolic diseases. Recent Advances: The primary goal of this review is to highlight recent advances and survey our current understanding of cell specific Nox enzymes' contributions to metabolic diseases.
FUTURE DIRECTIONS: We discuss the targeting of Nox enzymes as potential therapy and bring to light potential emerging areas Nox research, microparticles and epigenetics, in the context of metabolic disease.