Stimulation of mitochondrial fatty acid oxidation by growth hormone in human fibroblasts.
In vivo administration of GH induces lipolysis and lipid oxidation. However, it is not clear whether the stimulation of lipid oxidation is a direct effect of GH or is driven by increased substrate supply secondary to lipolysis. An in vitro bioassay has been established for assessing beta-oxidation of fatty acids in mitochondria, based on the measurement of conversion of tritiated palmitic acid to 5H2O by fibroblasts 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 stimulation was biphasic, with the oxidation rate increasing with increasing GH concentration to a peak response at 1.5 nmol/L and declining to a level not significantly different from control thereafter. Insulin-like growth factor-I at concentrations of up to 250 nmol/L had no significant effect on fatty acid oxidation. GH-binding protein attenuated the effect of GH. An anti-GH receptor (GHR) antibody (MAb263), which dimerizes the receptor and induces GH-like biological actions, significantly 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 for this effect. This bioassay is a practical tool for studying the regulatory effects of GH on lipid oxidation.
Leung
K C
KC
Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, New South Wales, Australia.
Ho
K K
KK
D000911:Antibodies, Monoclonal / Q000276:immunology; D002352:Carrier Proteins / Q000494:pharmacology; D002478:Cells, Cultured; D005227:Fatty Acids / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism*; D013006:Growth Hormone / Q000494:pharmacology*; D019382:Human Growth Hormone / Q000494:pharmacology*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D011986:Receptors, Somatotropin / Q000276:immunology
D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D005227:Fatty Acids; D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D013006:Growth Hormone; C051815:somatotropin-binding protein