STIMULATION OF MITOCHONDRIAL FATTY-ACID OXIDATION BY GROWTH-HORMONE IN HUMAN FIBROBLASTS

In vivo administration of GH induces lipolysis and lipid oxidation. Ho wever, it is not clear whether the stimulation of lipid oxidation is a direct effect of GH or is driven by increased substrate supply second ary to lipolysis. An in vitro bioassay has been established for assess ing beta-oxidation of fatty acids in mitochondria, based on the measur ement of conversion of tritiated palmitic acid to (H2O)-H-3 by fibrobl asts in culture. We have modified this assay to investigate whether GH stimulates fatty acid oxidation. GH stimulated oxidation of palmitic acid maximally by 26.7 +/- 2.5% (mean +/- SEM; P < 0.0001). The stimul ation was biphasic, with the oxidation rate increasing with increasing GR concentration to a peak response at 1.5 nmol/L and declining to a level not significantly different-from control thereafter. Insulin-lik e growth factor-I at concentrations of up to 250 nmol/L had no signifi cant effect on fatty acid oxidation. GH-binding protein attenuated the effect of GH. An anti-GH receptor (GHR) antibody (MAb263), which dime rizes the receptor and induces GH-like biological actions, significant ly stimulated fatty acid oxidation. Another anti-GHR antibody (MAb5), which prevents receptor dimerization, suppressed GH action. In summary , GH directly stimulated fatty acid oxidation, an action not mediated by insulin-like growth factor-I. Dimerization of GHRs was necessary fo r this effect. This bioassay is a practical tool for studying the regu latory effects of GH on lipid oxidation.