Integrative role of brain and hypothalamus in the control of energy balance.

Body weight regulation is one of the most important homeostatic mechanisms. In recent years many molecular players involved in the energy balance were identified. Although the discovery of leptin almost 15 years ago sparked a great enthusiasm that we will soon understand molecular pathways regulating body weight homeostasis, these expectations turned out to be premature. We know that main site of body weight homeostasis is the hypothalamus with four primary regions - arcuate, paraventricular and ventromedial nuclei, and lateral hypothalamus. Downstream from leptin, the most important signalling peptides are melanocortin, CART, neuropeptide Y and AgRP. Beside those, many other signalling pathways that include signalling by adipokines such as resistin and adiponectin, endocannabinoids in hypothalamus, glucocorticoids from adrenal glands, sex steroid hormones from the gonads and several peptides/hormones secreted by gastrointestinal tract are involved in the body weight homeostasis, and the real challenge for the future is how to understand the complicated interplay between all these molecules. This seems to be a daunting task, but with the new discoveries and with the use of the new molecular tools a rapid progress is being made. The real challenge for the future nevertheless remains how to interfere with these processes and how to help people with body weight problems that are not caused simply by sedentary life style, but also by the genetic make-up of these individuals.