Serum leptin concentrations during short-term administration of growth hormone and triiodothyronine in healthy adults: A randomised, double-blind placebo-controlled study

The regulation of adipose tissue mass and energy expenditure is currently s ubject to intensive research, which primarily relates to the discovery of l eptin. Leptin is a peptide, which is the product of the obese (ob) gene exp ressed in adipose tissue of several species including humans. Leptin is sup posed to serve both as an index of fat mass and as a sensor of energy balan ce [1,2]. Administration of recombinant murine leptin in ob/ob-mice, which do not produce leptin, decreases food intake and increases thermogenesis bo th of which result in a reduction in body weight and adipose tissue mass [1 ,3]. The calorigenic effect of leptin presumably acts through an increase i n sym pathetic outflow which in turn activates the beta 3 adrenergic recept or in brown adipose tissue [1,3]. The regulation and action of endogenous l eptin in humans are less well understood, and clinical grade recombinant hu man leptin is so far not available. Serum leptin correlates logarithmically with total body fat in both normal weight and obese subjects, which sugges t insensitivity to leptin in obese patients [4]. Furthermore, more rapid ex cursions in serum leptin have been reported following short-term changes in caloric intake [4] and administration of insulin [5]. Growth hormone (GH) exerts pronounced effects on lipid metabolism and resting energy expenditur e. The lipolytic actions of GH appear to involve both increased sensitivity to the beta-adrenergic pathway [6], and a suppression of adipose tissue li poprotein lipase activity [7]. The calorigenic effects of GH have been show n not only to be secondary to changes in lean body mass [8]. Growth hormone administration furthermore increases the peripheral conversion of thyroxin e to triiodothyronine [8], which may contribute to the overall actions of G H on fuel and energy metabolism. So far, little is known about the effects of GH and iodothyronines on serum leptin levels in humans. We therefore mea sured serum leptin levels and energy expenditure before and after the admin istration of GH and triiodothyronine, alone and in combination, in a random ized double-blind placebo-controlled study in healthy young male adults. Th e dose of triiodothyronine was selected to obtain serum levels comparable t o those seen after GH administration [8].