Regulation of body weight: what is the regulated parameter?

Despite dramatic variations in day to day intake and energy expenditure, weight remains relatively stable in most animals and humans. There are clear physiological responses to over and underfeeding suggesting that the body strives to maintain a constant weight. Despite this, for most humans and experimental animals, there is a tendency for weight to increase slowly over the lifespan. Recent increases in the prevalence of both obesity and anorexia nervosa suggest that factors other than homeostatic physiological mechanisms are important in determining body weight. Clearly reward pathways are activated by palatable food and evidence is emerging that energy balance can modulate these reward pathways and alter the salience of food related stimuli. Significant inhibitory control of reward pathways also comes from a number of brain regions involved in regulation of behavior. Finally there is strong evidence of the important role that social and environmental factors play in modulating both food intake and physical activity behaviors which in turn result in alterations in weight over time. While some aspects of these regulatory systems are within the conscious awareness of people, many, perhaps even most are not. The evidence then would suggest that weight is controlled by several complex regulatory systems that respond to internal metabolic and hormonal signals, hedonic properties of food, internal forces of valuation and self-control, and social factors. Each of these systems is likely 'regulated' and is important in ultimately determining body weight. Experimental paradigms that test one variable in one of these interrelated systems should, where possible control or at least consider the other systems in an effort to provide an integrated picture of weight regulation.