[The ob gene product (leptin)--a new hormone of adipose tissue]

Abstract

Obesity--an important problem in modern societies--is caused by energy balance dysregulation and produces numerous adverse effects on health. Recently a particular attention has been paid to molecular and physiological mechanisms in the development of obesity and to the signalling role of adipose tissue in energy stores maintenance on the hypothalamic level. Leptin, the obese gene product discovered in 1995, may play a key role in the feedback system between adipose tissue and the ventromedial nucleus of the hypothalamus (satiety centre). The level of ob gene expression in adipose tissue and plasma leptin concentrations in humans are highly correlated with BMI. So far no mutations in the ob gene in obese subjects have been reported therefore leptin molecule could be active. Despite markedly increased leptin levels found in obesity its central action decreasing food intake and increasing energy expenditure is hindered. Defective ob protein signalling to the brain may be due to receptor and post-receptor defects. Neuropeptide Y, the hypothalamic neurotransmitter involved in the maintaining of energy homeostasis, is a likely candidate for mediating leptin afferent signals. In adipose tissue, the level of ob mRNA is regulated by insulin and glucocorticoids--hormones responsible for glucose homeostasis as well as for the central regulation of feeding behaviour. Until now the character of interactions between leptin and other hormones that regulate energy balance is not known, neither is the exact nature of leptin hypothalamic receptor defect. Defining of the role of leptin in the regulation of satiety and energy expenditure will undoubtedly contribute to a better understanding of the pathogenesis of obesity and its related metabolic complications and may lead to a new treatment approach to human obesity based on leptin or its analogues. At present research work focuses on leptin receptor studies and on ob gene polymorphism and its expression in feeding disorders including obesity and anorexia nervosa. The ob gene is one of a few genes involved in energy balance, however, very promising one.