The growth hormone-dependent decrease in hepatic fatty acid synthase mRNA is the result of a decrease in gene transcription

Donkin, Shawn S.; McNall, Amy D.; Swencki, Bethany; Peters, J. L.; Etherton, Terry D.

doi:10.1677/jme.0.0160151

Cited by 33 publications

(20 citation statements)

References 22 publications

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“…GH given as a continuous infusion, thus mimicking the female secretory pattern of GH (6), resulted in increased FAS mRNA levels as observed in this study and in intact male rats (48). On the contrary, GH given as daily injections to ovariectomized female rats, mimicking the male secretory pattern of GH, decreased FAS mRNA expression (5). In this context, it is interesting to note that only GH given as a continuous infusion could fully restore triglyceride synthesis and VLDL secretion in Hx rats to those of normal rats (42).…”

Section: Discussionsupporting

confidence: 70%

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

Frick

Lindén

Améen

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

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. 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...

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Section: Discussionsupporting

confidence: 70%

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

Frick

Lindén

Améen

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

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“…The present study indicates that GH may enhance fatty acid synthesis. However, GH has been shown to acutely inhibit acetyl-CoA carboxylase activity (5) and decrease fatty acid synthase mRNA levels in the liver (16). There are also in vivo studies that show that GH stimulates ␤-oxidation in hepatocytes (10,17).…”

Section: Discussionmentioning

confidence: 99%

Direct effects of growth hormone on production and secretion of apolipoprotein B from rat hepatocytes

Lindén

Sjöberg

Asp³

et al. 2000

American Journal of Physiology-Endocrinology and Metabolism

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The aim of this study was to investigate the direct effects of growth hormone (GH) on production and secretion of apolipoprotein B (apoB)-containing lipoproteins from hepatocytes. Bovine GH (5-500 ng/ml) was given for 1 or 3 days to rat hepatocytes cultured on laminin-rich matrigel in serum-free medium. The effects of GH were compared with those of 3 nM insulin and 500 microM oleic acid. GH increased the editing of apoB mRNA, and the proportion of newly synthesized apoB-48 (of total apoB) in the cells and secreted into the medium changed in parallel. GH increased total secretion of apoB-48 (+30%) and apoB-48 in very low density lipoproteins (VLDL) more than twofold. Total apoB-100 secretion decreased 63%, but apoB-100-VLDL secretion was unaffected by GH. Pulse-chase studies indicated that GH increased intracellular early degradation of apoB-100 but not apoB-48. GH had no effect on apoB mRNA or LDL receptor mRNA levels. The triglyceride synthesis, the mass of triglycerides in the cells, and the VLDL fraction of the medium increased after GH incubation. Three days of insulin incubation had effects similar to those of GH. Combined incubation with oleic acid and GH had additive effects on apoB mRNA editing and apoB-48-VLDL secretion. In summary, GH has direct effects on production and secretion of apoB-containing lipoproteins, which may add to the effects of hyperinsulinemia and increased flux of fatty acids to the liver during GH treatment in vivo.

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“…demonstrated that GH administration via gene therapy (rAAV2/1 vector containing the GH1 gene) reversed the increased hepatic TG in animal models of alcoholic fatty liver disease after 6 weeks of alcohol exposure by reduced hepatic nSREBP-1c protein expression and stimulated hepatic AMPKα and PPARα activity 39 . In Donkin’s study, GH given as daily injections to ovariectomized female rats, mimicking the male secretory pattern of GH, decreased FAS mRNA expression 40 . On the contrary, GH treatment given by means of Alzet osmotic minipumps implanted subcutaneously, mimicking the female secretory pattern of GH, resulted in increases in SREBP-1c and hepatic expression of lipogenic enzymes in hypophysectomized rats 41 .…”

Section: Discussionmentioning

confidence: 98%

Growth hormone reverses dyslipidemia in adult offspring after maternal undernutrition

Zhu

Tang

Shen

et al. 2017

Sci Rep

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The abnormal intrauterine milieu of fetal growth retardation could lead to dyslipidemia in adulthood. Studies have shown that growth hormone (GH) therapy in small for gestational age (SGA) children would be beneficial for metabolic parameters. Here we investigated whether GH treatment introduced at adolescent period in SGA could reverse dyslipidemia during later life. SGA rat model was established by using semi-starvation treatment during the whole pregnancy. SGA or appropriate for gestational age (AGA) offspring were assigned to receive GH or normal saline (NS). Once-daily subcutaneous injections of GH were administered between 21–35 days of age. In adulthood, as compared to AGA, SGA showed: (1) decreased body weight and length; (2) increased serum triglycerides; (3) down-regulated hepatic AMPK-α1 but up-regulated SREBP-1c and ACC-1; (4) a significant reduction in histone H3 acetylation at the promoter of AMPK-α1. Exogenous GH administration led to a restoration of body weight and length and normalized serum triglycerides by reversing expression of AMPK-α1 and its targeted genes SREBP-1c and ACC-1, through increasing H3 acetylation at the promoter of AMPK-α1 in SGA in adult period. These results demonstrated positive effects on lipid metabolism by a short treatment course of GH in SGA adult period.

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The growth hormone-dependent decrease in hepatic fatty acid synthase mRNA is the result of a decrease in gene transcription

Cited by 33 publications

References 22 publications

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

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

Direct effects of growth hormone on production and secretion of apolipoprotein B from rat hepatocytes

Growth hormone reverses dyslipidemia in adult offspring after maternal undernutrition

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