GH, IGF-1 and insulin in the regulation of lipid and lipoprotein metabolism

Abstract

It is well known that growth hormone (GH) has profound effects on lipid and lipoprotein metabolism. Insulin-like growth factor-I (IGF-I) is believed to mediate some of the effects of GH via endocrine and paracrine mechanisms. Moreover, both GH and IGF-I are known to influence insulin secretion. The aim of the present study was to investigate the importance of IGF-I and insulin, respectively, for the effects of GH on lipid and lipoprotein metabolism. Hypophysectomised female rats were treated with GH, IGF-I, insulin or GH plus insulin for 7 days. Various aspects of lipid and lipoprotein metabolism were studied in adipose tissue (AT), skeletal muscle, heart and liver from these animals. GH treatment increased lipoprotein lipase (LPL) activity in heart and skeletal muscle. In adipose tissue (AT), IGF-I treatment markedly reduced, and insulin increased, LPL activity. IGF-I treatment of Hx rats decreased both basal and insulin-stimulated glucose incorporation in AT, an effect that could be ascribed to decreased plasma insulin levels in IGF-I treated rats. In contrast, IGF-I treatment increased insulin-stimulated glucose incorporation into glycogen in skeletal muscle, indicating that IGF-I directly stimulates glucose uptake and metabolism in skeletal muscle. GH increased the hepatic triglyceride content and secretion rate, an effect that was blunted by combined insulin treatment, suggesting that insulin does not mediate these effects of GH. GH treatment increased the gene expression of two genes important in hepatic fatty acid synthesis, fatty acid synthase (FAS) and stearoyl CoA desaturase (SCD). The effects of GH on editing of apoB mRNA, SCD mRNA, and probably FAS mRNA, could partly be mediated by increased insulin levels. In order to study the effects of prolonged high levels of GH on lipid and lipoprotein metabolism, bGH transgenic mice were studied. In the bGH transgenic mice serum cholesterol levels were higher and serum triglyceride levels were lower. Moreover, transgenic mice showed a marked reduction in cholesterol and triglyceride content of the VLDL fraction and increased cholesterol content of the LDL and HDL fractions. The hepatic triglyceride secretion rate was reduced. LPL activity was increased in heart and adipose tissue. The difference in serum triglycerides between bGH transgenic females and gender controls was abolished after fat feeding. In conclusion, most of the effects of GH on lipid and lipoprotein metabolism are not mediated by IGF-I or insulin. IGF-I seems to have direct effects in skeletal muscle. In adipose tissue, IGF-I has indirect effects via changed insulin secretion.