Leptin: fundamental aspects

The discovery of leptin, the product of the ob gene, has led to major devel opments in understanding the regulation of energy balance. It is now recogn ised that leptin is produced in several organs additional to white adipose tissue, including brown fat, the placenta and fetal tissues (such as heart and bone/cartilage). The hormone has multiple functions-in inhibiting food intake, in the stimulation/maintenance of energy expenditure, as a signal t o the reproductive system and as a 'metabolic' hormone influencing a range of processes (for example, insulin secretion, lipolysis, sugar transport). The production of leptin by white fat is subject to a number of regulatory influences, including insulin and glucocorticoids (which are stimulatory), and fasting and B-adrenoceptor agonists (which are inhibitory). A key role in the regulation of leptin production by white fat is envisaged for the sy mpathetic system, operating through BB-adrenoceptors. The leptin receptor g ene is widely expressed, with the several splice variants exhibiting differ ent patterns of expression. The long form variant (Ob-Rb) is expressed part icularly in the hypothalamus, although it is being increasingly identified in other tissues. Leptin exerts its central effects through several neuroen docrine systems, including neuropeptide Y, glucagon-like peptide-1, melanoc ortins, corticotrophin releasing hormone (CRH) and cocaine- and amphetamine -regulated transcript (CART). In essence, the leptin system now appears hig hly complex, the hormone being involved in a range of physiological process es in a manner far transcending the initial lipostatic concept. This comple xity may reduce the potential of the leptin system as a target for anti-obe sity therapy.