Abstract
Obesity is a chronic disease associated with serious health hazards. A review of evidence indicates that it is neither a simple failure nor the question of willpower. Traditional weight reducing methods including diet, exercise or behavioural modification are rarely effective over the long term. Thus there is a continued need for safe and effective treatment of obesity which tends to be quite possible in the near future provided that our management should be targeted on primary cause of the disturbances of food intake and energy balance. The recent studies on pathophysiology of appetite and energy balance regulation, in particular the discovery of leptin and studies on genetic background of obesity have led to major developments in our understanding of obesity pathogenesis. It is now recognised that CNS and hypothalamus are key structures involved in the control of body weight regulation. A variety of neuromodulators stimulate food intake like NPY, orexins, MCH (Melarun-Concentrating-Hormone). In contrast a large number of peptides and neurotransmitters including leptin, biogenic amines or α-MSH exert the opposite effect. The role of uncoupling proteins has recently been understood. They are believed to increase energy expenditure by disturbing the process of ATP synthesis. The great progress in studies on obesity resulted in new molecular targets for antiobesity agents. They include marketed recently in our country sibutramine, and other promising compounds being currently under clinical investigation such as β3 agonists and 5HT2C agonists. Data from animal studies suggest that other agents including antagonists of neuropeptide Y Y5 receptors or melanocortin MC4-R receptors agonists may turn out to be effective as well. However further research is needed to understand the individually different genetic and pathophysiological basis of obesity.