부산대학교 도서관

Leptin is primarily secreted by the adipose tissue. It binds not only to hypothalamic structures involved in energy regulation but also to many peripheral tissues including the liver. Leptin circulates in free and receptor-bound forms. Both components are differentially regulated under various pathophysiological conditions and serve different physiological functions. They are released from adipose tissue but previous data suggest an additional formation outside the fat compartment. Here we tested the contribution of the liver in binding and modulating leptin in the circulation.In vivoexperiments were performed with radioactive labelled leptin with and without pretreatment with unlabelled leptin in freely moving, chronic intravenously cannulated male rats. Livers were investigated by immunohistochemistry andin situhybridization and immunoblotting was performed, followed byex vivoliver perfusion studies with human recombinant leptin.Inin vivoexperiments radioactively labelled leptin (at low concentrations) is avidly bound to rat liver (greater than 80% of basal serum values 90 min following i.v. infusion). Pre-treatment with excess of unlabelled leptinin vivorevealed a rapid hepatic down-regulation of leptin receptor isoforms when tested byin situhybridization, immunoblotting or immunohistochemistry.Ex vivoperfusion of rat liver with human recombinant leptin induced a dose- and time-dependent formation of receptor-bound leptin in the perfusate.The present data support an active role of the liver in the modulation of the leptin signal through different regulation of the soluble leptin receptor, the bound and free forms of the hormone, which may have important implications for leptin's central efficacy and the development of‘leptin resistance’.Eur J Clin Invest 2004; 34 (12): 831 –837 [ABSTRACT FROM AUTHOR]