Opposing effects of glucagon and triiodothyronine on the hepatic levels of messenger ribonucleic acid S14 and the dependence of such effects on circadian factors.

Kinlaw, William B.; Schwartz, Harold L.; Towle, Howard C.; Oppenheimer, Jack H.

doi:10.1172/jci112665

Cited by 32 publications

(11 citation statements)

References 22 publications

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“…In the present experiments, how¬ ever, in which a wide dose range of T3 was adminis¬ tered, marked stimulatory actions of T3 were achieved only at 72 h after daily T3 replacement was commenced; furthermore, a clear dose-de¬ pendent effect was evident at this time point. Stimulatory actions of T3 treatment in the euthy¬ roid state were also demonstrated in the present studies, in accord with a report of a 2-fold increase in Spot 14 mRNA 1.5 h after injection of T:i (200 (ig) in the euthyoid rat (17). In contrast to the absence of a sustained effect of T3 treatment of the hypothy¬ roid rat at 6 h, a dose-dependent stimulation of Spot 14 mRNA was induced in the euthyroid rat at this time point.…”

Section: Discussionsupporting

confidence: 93%

Effect of hypothyroidism and thyroid hormone treatment of the rat on hepatic Spot 14 and thyroxine binding prealbumin mRNAs

Franklyn

King²,

Ahlquist³

et al. 1989

Acta Endocrinologica

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We have examined the influence of hypothyroidism and thyroid hormone replacement on hepatic levels of Spot 14 and thyroxine binding prealbumin mRNAs determined by dot hybridization and by Northern blot hybridization to specific complementary DNA probes. A marked reduction in Spot 14 mRNA was demonstrated in hypothyroidism, compared with the euthyroid state. T3 replacement of hypothyroid rats, using a wide dose range of T3 (1\p=n-\20 \g=m\g) and 6 and 72 h time points, demonstrated no sustained effect at 6 h, but a dose-dependent stimulation of Spot 14 mRNA at 72 h after daily treatment with T3 was commenced. In contrast, no effect of hypothyroidism or T3 replacement on hepatic levels of thyoxine binding prealbumin mRNA was demonstrated, indicating the specificity of thyroid hormone action. T3 treatment of euthyroid rats was also associated with a dose-related stimulation of Spot 14 mRNA levels. The effect of hypothyroidism and T3 treatment of the rat on hepatic Spot 14 mRNA contrasts with divergent regulatory influences of thyroid status in the anterior pituitary and ventricular myocardium demonstrated using identical animal models, indicating the tissue specific influences of thyroid status.Thyroid hormones exert regulatory effects on the growth, differentiation and metabolism of most tis¬ sues of higher organisms. There is overwhelming evidence that the cellular actions of thyroid hor¬ mones are mediated by nuclear receptors (1). High affinity nuclear binding sites for tri-iodothyronine have been demonstrated in most mammalian tis¬ sues and recent cloning of c-erb-A (c)DNA suggests that T, receptors are encoded by these cellu¬ lar proto-oncogenes (2). Multiple c-erb-A cDNAs have now been cloned and classified according to structure into two major groups, designated a and ß, each class comprising several members (3). The function of these multiple thyroid hormone bind¬ ing proteins is not clear, but differences in their be¬ haviour and tissue distribution may provide an ex¬ planation for the tissue and gene specific regula¬ tory actions of T3.We have reported previously regulatory effects of thyroid status on gene expression in the rat anterior pituitary (4, 5) and ventricular myocar¬ dium (6). These studies have indicated the speci¬ ficity of thyroid hormone action, with a biphasic (stimulatory then inhibitory) time-dependent ef¬ fect of T.¡ treatment of the hypothyroid rat on thyrotrophin messenger RNAs in the pituitary, con¬ trasting with simple stimulatory influences on growth hormone and prolaction mRNAs, and in the ventricular myocardium, opposite regulatory effects of thyroid status on a and ß myosin heavy chain mRNAs.

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Section: Discussionsupporting

confidence: 93%

Effect of hypothyroidism and thyroid hormone treatment of the rat on hepatic Spot 14 and thyroxine binding prealbumin mRNAs

Franklyn

King²,

Ahlquist³

et al. 1989

Acta Endocrinologica

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“…Similarly, activation of PKA inhibited glucose-induced expression of the S14 (27) and L-PK (28) genes, although for the former, it has been attributed to an effect on glucose metabolism (9) and for the latter to an effect on glucokinase activity. Indeed, the cAMP inhibitory effect on L-PK gene expression was lost in a hepatoma cell line expressing hexokinase II rather than glucokinase (29).…”

Section: Resultsmentioning

confidence: 99%

AMP-activated Protein Kinase Inhibits the Glucose-activated Expression of Fatty Acid Synthase Gene in Rat Hepatocytes

Foretz¹,

Carling²,

Guichard³

et al. 1998

Journal of Biological Chemistry

232

172

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Although it is now clearly established that a number of genes involved in glucose and lipid metabolism are up-regulated by high glucose concentrations in both liver and adipose tissue, the signaling pathway arising from glucose to the transcriptional machinery is still poorly understood. We have analyzed the regulation of fatty acid synthase gene expression by glucose in cultured rat hepatocytes. Glucose (25 mM) induces an activation of the transcription of the fatty acid synthase gene, and this effect is markedly reduced by incubation of the cells with okadaic acid, an inhibitor of protein phosphatases 1 and 2A. A similar reduction in glucoseactivated fatty acid synthase gene expression is obtained by incubation with 5-amino-imidazolecarboxamide riboside, a cell-permeable activator of the AMPactivated protein kinase. Taken together, these results indicate that the glucose-induced expression of the fatty acid synthase gene involves a phosphorylation/dephosphorylation mechanism and suggest that the AMP-activated protein kinase plays an important role in this process. This is the first evidence that implicates the AMP-activated protein kinase in the regulation of gene expression. AMP-activated protein kinase is the mammalian analog of SNF1, a kinase involved in yeast in the transcriptional regulation of genes by glucose.Although it is now clearly established that a number of genes involved in glucose and lipid metabolism are up-regulated by high glucose concentrations in both liver and adipose tissue (for review, see Refs. 1 and 2), the signaling pathway arising from glucose to the transcriptional machinery is still poorly understood. There is general agreement on the fact that glucose has to be metabolized to stimulate the transcription of lipogenicrelated genes such as L-pyruvate kinase, fatty acid synthase (FAS), 1 acetyl-CoA carboxylase (ACC), and S14 (3-5). In previous papers, we have proposed that glucose-6-phosphate could be the signal metabolite for the glucose-induced FAS transcription (3, 5, 6) and therefore for other genes belonging to the same class. This hypothesis was challenged by Doiron et al. (7) who proposed that the signal metabolite was xylulose-5-phosphate. However, whatever the metabolite, the link between the glucose signal and the activation of gene transcription remains unknown.Phosphorylation/dephosphorylation processes are one of the major mechanisms involved in the regulation of glucose and lipid metabolism both at the cellular and molecular levels in eukaryotic cells. It is now well established that many transcription factors have their activity regulated by phosphorylation through a modification of their DNA binding activity, their transactivating capacity, or their subcellular localization (8).In cultured hepatocytes, it has been shown that okadaic acid, an inhibitor of phosphatases 1 and 2A led to the inhibition of glucose stimulation of S14 gene transcription (9). Further experiments with calyculin, a much more potent inhibitor of protein phosphatase 1 than okadaic acid, suggest th...

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“…Specifically, the level of Thrsp mRNA in white adipose tissue, brown adipose tissue, and liver is elevated when de novo fatty acid synthesis is induced by dietary and hormonal stimuli (Freake and Oppenheimer, 1987, Jump et al, 1984, Jump and Oppenheimer, 1985, Kinlaw et al, 1986, Narayan et al, 1984, Towle and Mariash, 1986). To study the role of the Thrsp protein in de novo lipogenesis, we created a Thrsp null mouse and found that the rate of hepatic lipogenesis was normal but mammary gland lipogenesis was markedly reduced (Zhu et al, 2001, Zhu et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

The Thrsp null mouse (Thrsptm1cnm) and diet-induced obesity

Anderson

Zhu

Metkowski

et al. 2009

Molecular and Cellular Endocrinology

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We created a Thrsp (Spot 14 or S14) null mouse (Thrsp tm1cnm ) to study the role of Thrsp in de novo lipid synthesis. The Thrsp null mouse exhibits marked deficiencies in de novo lipogenesis in the lactating mammary gland. We now report the Thrsp gene deletion affects body weight and glucose tolerance associated with increased insulin sensitivity. By postnatal day 150 the rate of first generation C57BL/6J backcross Thrsp null mouse weight gain slowed compared to wild type animals. This was due to changes in body fat mass. We studied mice backcrossed for 5 and 11 generations. The weight difference between the null and wild type adult mice diminished with progressive backcross generations. In conclusion the Thrsp gene is involved in the regulation of diet induced obesity and deletion of Thrsp leads to an improvement in age associated glucose tolerance.

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Opposing effects of glucagon and triiodothyronine on the hepatic levels of messenger ribonucleic acid S14 and the dependence of such effects on circadian factors.

Cited by 32 publications

References 22 publications

Effect of hypothyroidism and thyroid hormone treatment of the rat on hepatic Spot 14 and thyroxine binding prealbumin mRNAs

Effect of hypothyroidism and thyroid hormone treatment of the rat on hepatic Spot 14 and thyroxine binding prealbumin mRNAs

AMP-activated Protein Kinase Inhibits the Glucose-activated Expression of Fatty Acid Synthase Gene in Rat Hepatocytes

The Thrsp null mouse (Thrsptm1cnm) and diet-induced obesity

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