Oxidative Stress and Obesity: The Chicken or the Egg?

Abstract

Over the past 30 years much research has focused on elucidating mechanisms linked to progression of obesity and its cardiovascular comorbidities. As the central dogma regarding the pathophysiology of obesity unfolds, it is evident that the expansion of visceral adipose tissue caused by overconsumption of nutrients plays a central role. As visceral fat stores expand, adipocytes generate increasing levels of reactive oxygen species (ROS) that incite increased expression and secretion of inflammatory adipokines (1–3). Oxidative stress leads to insulin resistance within adipose tissue as well as in peripheral tissues. Insulin resistance is one of the hallmarks of obesity and accounts for many of its comorbidities, including hypertension (4). Accumulation of oxidative stress in adipose tissue is one of the early events in the development of metabolic syndrome in obesity (5). On the other hand, weight loss by calorie restriction and/or exercise can ameliorate the state of oxidative stress (6). Nonetheless, a cause and effect relationship between oxidative stress and obesity is not well understood. NADPH oxidase is a major contributor to oxidative stress in many tissues, including adipose tissue and the vasculature (5,7,8). Conversely, factors causing oxidative stress, such as angiotensin II, that induce insulin resistance do not necessarily induce body weight gain (9). Therefore, whether oxidative stress, per se, leads to weight gain is an important gap in our understanding of the pathophysiology of obesity. In this issue, Youn et al. (10 …