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

Abstract

. Interaction between growth hormone and insulin in the regulation of lipoprotein metabolism in the rat. Am J Physiol Endocrinol Metab 283: E1023-E1031, 2002. First published July 30, 2002 10.1152/ajpendo.00260.2002The 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 IT IS WELL KNOWN THAT GROWTH HORMONE (GH) has marked effects on lipid and lipoprotein metabolism (1, 30). GH also increases secretion (27, 32) and plasma levels of insulin in humans and rats (31,32,37,44). Moreover, GH increases DNA synthesis and proliferation of ␤-cells and insulin secretion in vitro (27), showing that GH enhances ␤-cell function independently of its insulin-antagonistic action (34,35,45). The increased serum insulin levels and the insulin-antagonistic effect of GH may be of importance for several effects of GH in vivo, but few studies have addressed this question (31,36). Treatment of normal rats with the combination of insulin and GH results in an additive effect on body weight gain. However, GH treatment antagonizes the stimulatory effects of insulin on food intake and adipose tissue weight, indicating a complex interaction between GH and insulin (36).The interaction of insulin and GH in the regulation of lipid and lipoprotein metabolism is of special interest, because similar effects of GH and chronic hyperinsulinemia...

Effects of gender and GH secretory pattern on sterol regulatory element-binding protein-1c and its target genes in rat liver

“…The level of ␤-actin mRNA was not regulated by sex or the various hormonal treatments used in this study. The RNA probes were hybridized to the sample RNA by use of an RPA III kit (Ambion), and the protected fragments were separated and detected as described before (1,14). The amounts of the transcripts are expressed as the ratio between the gene of interest and the internal control (␤-actin).…”

“…Our laboratory (14) has shown that a continuous infusion of GH to Hx rats increases hepatic triglyceride secretion and content as well as mRNA expression of sterol regulatory element-binding protein-1c (SREBP-1c) and the lipogenic enzymes fatty acid synthase (FAS) and stearoylCoA desaturase-1 (SCD-1). SREBP-1c is known to activate the transcription of both FAS and SCD-1, as well as acetylCoA carboxylase-1 (ACC1) and the rate-limiting enzyme in glycerolipid formation, glycerol-3-phosphate acyltransferase (GPAT) (20,43).…”

“…Moreover, insulin treatment increases hepatic LXR␣ expression (48). It is therefore conceivable that the effect of GH on the hepatic expression of SREBP-1c and its downstream target genes involved in fatty acid synthesis (13,14,49,50) also would be mediated through changes in LXR␣ expression levels (20,43).…”

Effect of growth hormone on fatty acid synthase gene expression in porcine adipose tissue cultures

“…One possible candidate is the sterol regulatory element binding protein (SREBP)-1c, a member of the helix-loop-leucine zipper family of transcription factors, which has been reported to play a pivotal role in mediating the effects of insulin in liver (Foufelle and Ferré, 2002). Frick et al (2002) observed that when growth hormone was administered to rats for 7 days there was increased expression of FAS and SREBP-1c in the livers of the rats. Insulin and growth hormone had no additive effects on these genes, instead insulin blunted the effect of growth hormone on SREBP-1c mRNA.…”

“…In contrast to liver, adipose tissue expression of FAS and SREBP-1c mRNA was not influenced by growth hormone. Frick et al (2002) concluded that the increased hepatic expression of lipogenic enzymes after growth hormone treatment may be explained by increased expression of SREBP-1c and insulin does not mediate the effects of growth hormone but inhibits the stimulatory effect of growth hormone on hepatic SREBP-1c expression and triglyceride secretion rate. The same observation was made by Louveau and Gondret (2004) who treated isolated porcine adipocytes with growth hormone and insulin and found that the regulation of lipogenesis appears not to involve changes in SREBP-1 mRNA levels.…”