White adipose tissue (WAT) plays a crucial role in the maintenance of healthy metabolic profile. To this effect, WAT lipid storage capacity expands in response to nutrient influx after physiological caloric ingestion. However, when confronted by a chronic surplus in caloric intake, WAT mass will increase in a pathological manner. Pathological WAT is characterized by insufficient capillarization and the development of inflammation and oxidative stress that promote the onset of insulin resistance and Type 2 diabetes mellitus (T2DM). The objective of this thesis is to review current knowledge about the WAT adaptive responses to caloric excess and their links to oxidative radicals. The three papers presented in this thesis establishes the role of the reactive oxygen species producing NADPH oxidase 4 (NOX4) in the processes that modulate WAT expenditure: neo-capillarization, hypoxia-mediated signaling, inflammatory signals and adipocyte differentiation, and examines the molecular pathways linking NOX4 to the development of insulin resistance. Taken together, the works presented in this thesis afforded the first insight into the importance of NOX4 in WAT pathophysiology. These results provided a solid basis for further studies aimed at uncovering the role of NOX4 in the modulation of the complex network that governs WAT redox homeostasis and metabolic health and to evaluate the potential of NOX4 as a novel therapeutic target in obesity and T2DM.