[Leptin--the key to obesity?]

Obesity is at present one of the most important health risk factors in developed countries. Several studies show significant involvement of genetic factors. A gene called ob is active in the adipose tissue and its product leptin is secreted from adipocytes. Fully functional leptin receptors (encoded by the ob/R gene, also db) have been found in highest numbers in the hypothalamus and therefore it was suggested that it is the leptin plasma level which in forms the brain about total body fat mass and calories intake. Using this pathway it can directly influence a balance between food intake and energy expenditure. The phenotype of ob/ob mutant mice is characterized by severe obesity, NIDDM (non insulin dependent diabetes mellitus), diminished fertility and hypothermia. Db/db mutant mice show a similar phenotype, here the defect lies in the block of leptin receptor downstream signalling. After leptin administration, it was possible to correct the defect only in the ob/ob, but not db/db mice. There is a positive correlation between body mass index and leptin plasma level in humans and no obese patients have been found defective in leptin production or producing or producing ineffective leptin. Human obesity might be connected to a defect of leptin receptor or to its altered signal transduction. Leptin administration is therefore not important in human obesity treatment.