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Stimulation of Mitochondrial Fatty Acid Oxidation by Growth Hormone in Human Fibroblasts¹

Garvan Institute of Medical Research, St. Vincent’s Hospital, Sydney, New South Wales 2010, Australia

Address all correspondence and requests for reprints to: Dr. Ken K. Y. Ho, Associate Professor of Medicine, Garvan Institute of Medical Research, St. Vincent’s Hospital, 384 Victoria Street, Sydney, New South Wales 2010, Australia. E-mail: k.ho{at}garvan.unsw.edu.au

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 ß-oxidation of fatty acids in mitochondria, based on the measurement of conversion of tritiated palmitic acid to ³H₂O 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.

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