The Central Control of Energy Metabolism: Hypothalamic Obesity Is Not One Disease

Abstract – Background: The hypothalamus, a neuroendocrine gland centrally in the brain, weighs only on average 4 grams but is the captain on the ship of our energy balance. In the hypothalamus, signals of the satiety and hunger hormones are integrated and individuals with a dysfunctional hypothalamus develop obesity. The hypothalamus, however, integrates much more than the satiety and hunger hormones, and hypothalamic obesity may be the result of a combination of factors. Summary: The consequences of hypothalamic dysfunction can be categorized in six different domains. By systematically evaluating each domain, the underlying cause for obesity may be better understood, and doors for successful management can be opened. The different domains are; pituitary gland dysfunction, behavioral problems, disturbance of the circadian rhythm, hyperphagia, low resting energy expenditure, and temperature dysregulation. All of these domains may contribute to the development of obesity and may be more or less present in the individual patient. Key Messages: Hypothalamic obesity is not one disease, but different underlying contributing factors may be present. Consequently, hypothalamic obesity management is not one-size-fits-all but needs to be personalized. In this paper, the current state of the art for both the diagnostics and approach of acquired hypothalamic obesity is reviewed.