FIGURE 1.

The energy balance model of obesity posits that body weight is regulated by the brain in response to external signals from the food environment that are integrated with internal signals to control food intake below our conscious awareness. Increased prevalence of obesity has resulted from changes in the food environment leading to increased food intake and circulating fuels. Hormones, including insulin, respond to nutrient intake and absorption to direct the flow of metabolic fluxes into and out of various organs and provide signals to the brain that control food intake. Energy supply to organs such as liver and muscle increases, which supports their increased growth during the development of obesity and can result in ectopic lipid accumulation. Signals indicating the energy status of various organs are sensed by the brain to control food intake by mechanisms that remain to be fully elucidated. Oxidation of carbohydrate, fat, and protein provides the body with its energy needs, which increase as obesity develops. Adaptations of metabolic fuel selection as well as changes in the endocrine milieu ensure that partitioning of overall energy imbalances are primarily reflected as changes in adipose tissue triglyceride storage regardless of diet composition. Inherited variation in the operation of these processes, particularly those in the brain, are responsible for a substantial proportion of the interindividual difference in susceptibility or resistance to developing obesity in a particular environment. Thick blue arrows indicate the flow of energy. GI, gastrointestinal.