A sedentary lifestyle, in conjunction with excessive food intake, is contributing to the worldwide increasing prevalence of obesity. Overeating is associated with insulin resistance, hypertension, dyslipoproteinaemia and endothelial dysfunction. A complicated network of cellular mechanisms has recently been suggested to play a central role in the control of energy homeostasis and metabolic response to overfeeding in animals. Understanding these mechanisms will substantially increase our knowledge about the physiological and biochemical factors leading to obesity and insulin resistance in humans.