Obesity is the result of the accumulation of excess body fat and not simply excess weight that can be muscle or fat. Adipocytes function in the adaptation to starvation, in exercise energetics, and in the immune defense against pathogens. Sustained positive energy balance results in excessive accumulation of adipocytes, which, in the abdomen, leads to chronic inflammation. Although informative studies have been performed with cultured adipocytes, an integrative approach to the regulation of abdominal adipose tissue involves feedback from autocrine and paracrine effectors secreted by adipocytes, the immune system, and blood flow through adipose tissue. Numerous adipokines, chemokines, and cytokines feed back to other bodily systems to regulate both energy balance and immune function. Studies of the interactions of the gastrointestinal tract and the central nervous system, as well as psychophysiological considerations of reward circuitry in the central nervous system, have shown a general adaptation to starvation that is opposed to those strategies being proposed for the prevention and treatment of obesity, ie, food restriction and increased physical activity. The obesogenic environment of highly palatable foods with hidden fats and sugars can promote metabolic syndrome and obesity, whereas fruit and vegetables with antiinflammatory phytochemicals can counteract metabolic syndrome. Therefore, a plant-based diet and the seamless integration of increased physical activity and social support to alter modern diets and lifestyles hold out the greatest hope for the solution of the obesity epidemic. Both public health and medical nutrition approaches can benefit from this integrative view of obesity.