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Am J Physiol Endocrinol Metab 283: E1023-E1031, 2002. First published July 30, 2002; doi:10.1152/ajpendo.00260.2002
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Vol. 283, Issue 5, E1023-E1031, November 2002

Interaction between growth hormone and insulin in the regulation of lipoprotein metabolism in the rat

Fredrik Frick1,*, Daniel Lindén1,*, Caroline Améen1, Staffan Edén1, Agneta Mode2, and Jan Oscarsson1

1 Department of Physiology, Göteborg University, S-405 30 Göteborg; and 2 Department of Medical Nutrition, Karolinska Institutet, Novum, S-141 86 Huddinge, Sweden

The importance of insulin for the in vivo effects of growth hormone (GH) on lipid and lipoprotein metabolism was investigated by examining the effects of GH treatment of hypophysectomized (Hx) female rats with and without concomitant insulin treatment. Hypophysectomy-induced changes of HDL, apolipoprotein (apo)E, LDL, and apoB levels were normalized by GH treatment but not affected by insulin treatment. The hepatic triglyceride secretion rate was lower in Hx rats than in normal rats and increased by GH treatment. This effect of GH was blunted by insulin treatment. The triglyceride content in the liver changed in parallel with the changes in triglyceride secretion rate, indicating that the effect of the hormones on triglyceride secretion was dependent on changed availability of triglycerides for VLDL assembly. GH and insulin independently increased editing of apoB mRNA, but the effects were not additive. The expression of fatty-acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD-1), and sterol regulatory element-binding protein-1c (SREBP-1c) was increased by GH treatment. Insulin and GH had no additive effects on these genes; instead, insulin blunted the effect of GH on SREBP-1c mRNA. In contrast to the liver, adipose tissue expression of SREBP-1c, FAS, or SCD-1 mRNA was not influenced by GH. In conclusion, the increased hepatic expression of lipogenic enzymes after GH treatment may be explained by increased expression of SREBP-1c. Insulin does not mediate the effects of GH but inhibits the stimulatory effect of GH on hepatic SREBP-1c expression and triglyceride secretion rate.

apolipoprotein B; apolipoprotein E; apoB mRNA editing; triglyceride secretion; sterol regulatory element-binding protein-1; fatty-acid synthase; stearoyl-CoA desaturase; liver; adipose tissue

* Both authors contributed equally to this article.




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