Depot-Biased ROS: A Middleman in Adipose-Driven Cardiovascular Disease

The metabolic syndrome is a collection of disorders involving adipose tissue dysfunction, culminating in cardiovascular disease. Oxidative stress describes the state of elevated pro-oxidative processes generating reactive oxygen species (ROS) as opposed to antioxidant mechanisms curbing their production. In the context of metabolic homeostasis, ROS play a double-faceted role. While ROS are important signaling molecules for adipogenesis and adipose insulin sensitivity, exaggerated ROS production, as is the case in the metabolic syndrome, is fraught with undesirable cardiometabolic effects. Adipose tissues experience depot-biased oxidative stress originating from the mitochondrial electron transport chain and/or depot-specific nicotinamide adenine dinucleotide phosphate oxidase subtype. ROS interact with polyunsaturated fatty acids to form lipid peroxides that are transformed into reactive aldehyde species in a depot-biased manner. Visceral adipose depots are especially prone to oxidative stress as opposed to subcutaneous adipose. On the other hand, mitochondrial uncoupling processes of brown and beige adipose tissues provide a protective mechanism in the face of oxidative stress and its associated deleterious pro-inflammatory processes, especially evident in epicardial adipose tissues. Other adipose depots harbor different mechanisms of ROS generation and dissipation, where the genomic, lipidomic, and phenotypic signatures of adipose tissues dictate their unique propensity to oxidative stress as well as their respective response to it. In this chapter, we summarize the mechanisms and consequences of ROS production in the different phenotypes of adipose tissues as they relate to metabolically driven cardiovascular dysfunction.