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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although the molecular basis of thyroid hormone action remains obscure, a growing body of evidence has suggested that triiodothyronine (T3) action is initiated at a set of specific nuclear receptor sites. The physiologic significance of these T3-binding sites is supported by four lines of evidence: 1) the high-affinity, limited-capacity binding of T3; 2) the relationship between binding affinity of thyroid hormone analogs and hormonal potency; 3) the correlation of concentration of nuclear receptor and physiologic response in various tissues; 4) the relationship between receptor occupancy and physiologic response. While the levels of hepatic nuclear receptor do not change in response to T3, recent evidence indicates receptor concentration is markedly reduced by partial hepatectomy, starvation, or administration of glucagon. This reduction results in a decrease in the response of malic enzyme to T3, but leaves the response of alpha-glycerol phosphate dehydrogenase unimpaired. Thus, specific control of thyroid responses by modulating receptor concentration may occur. Occupancy of hepatic receptors by T3 is associated with increases in both the rate of formation and steady-state concentration of poly(A)-containing mRNA. The values of these two parameters in the euthyroid rat liver were approximately 60--80% greater than values in hypothyroid animals. Analyses of the sequence and frequency complexity of poly(A)-containing mRNA from euthyroid and hypothyroid rats revealed no major changes in either the qualitative or quantitative distribution of mRNA sequences. Although it is recognized that the levels of certain specific species of mRNA (ie, alpha 2u-globulin) are altered as a result of thyroid hormone action, these data strongly indicate a concomitant generalized increase in the production of all major classes of mRNA.
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PMID:Interaction of thyroid hormones with target tissues: effects of hepatic mRNA population. 23 83

Thyroid hormone nuclear receptor molecules have been characterized as proteins of approximately 49,000 molecular weight existing in cells attached to chromatin and with 4000-8000 copies per nucleus. They bind T3 with Ka of 0.2 X 10(10) l/mol and show microheterogeneity on isoelectric focusing. Hormone responsiveness varies with receptor content in the nucleus and occupancy of receptor by T3. Recent investigations have shown that the receptors are part of the v-erbA related super family of nuclear hormone receptors. At least two types of T3 receptors (TR) exist, one coded by a gene on chromosome 3 (TR beta) and a second coded on chromosome 17 (hTR alpha). Receptors are low in the fetus and, in the adult, are dramatically reduced by starvation, illness and glucagon. Receptors function through binding of T3 or other hormone analogs to a domain in the carboxyl portion of the protein, and binding of the receptor-T3 complex through 'DNA-fingers' to specific response elements as enhancers and located in the 5'-flanking DNA of thyroid hormone responsive genes. Extensive studies on regulation of rat growth hormone have suggested binding of receptor or associated factors to several positions in the 5'-flanking DNA, and recent studies suggest that a crucial area may be a 15 bp segment between bases -179 and -164. Abnormal receptors are believed to be responsible for the syndrome of generalized resistance to thyroid hormone action, but it is yet unclear as to which form (or forms) of the receptor is abnormal in this syndrome.
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PMID:Thyroid hormone nuclear receptors and their role in the metabolic action of the hormone. 249 27

Many studies have shown alterations in the number of nuclear triiodothyronine receptor (NT3R) under pathophysiologic situations. Most of these studies were performed on the rat liver and it is not known whether NT3R in different tissues exhibits an alteration similar to that in the liver. We compared the change of nuclear receptor capacity for T3 in the liver and kidney during starvation and after T3 injection. Fasting for 72 h decreased maximal binding capacity (Cmax) in the rat liver receptor to 67% of the control, while it did not significantly change Cmax in the kidney. These changes in Cmax were parallel to those of nuclear protein concentrations in both tissues. Daily sc injection of T3 (20 micrograms/100 g body weight) for 3 days also caused the different alteration of Cmax in the liver and kidney. After T3, hepatic NT3R increased to 182% of the control, but renal NT3R increased only to 136%. Association constants were the same in all groups. These results show that changes of NT3R capacity under some conditions vary in different tissues.
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PMID:Different alterations of nuclear triiodothyronine receptor capacity in liver and kidney induced by starvation and triiodothyronine administration. 298 41

We have determined the individual effects of postoperative fasting, surgical/anesthetic factors, acute uremia (AU), and regenerating liver (RL) on nucleoplasmic (NP; 0.15 M KCl-extractable) and chromatin-bound (CB; 0.4 M KCl-extractable) rat liver T3 receptors. AU and RL rats were studied 24 h after bilateral nephrectomy (blood urea nitrogen, 128 +/- 13 mg/dl) or two thirds hepatectomy, respectively. The effects of postoperative fasting were assessed by comparison of normal rats (N) with control rats (N6) pair-fed to match the caloric intake of the AU and RL rats. Surgical/anesthetic effects were determined by comparison of N6 rats with sham-operated pair-fed rats (S6). The effects of AU or RL were obtained by comparison with S6 controls. Changes in mean body weight attributable to fasting (N6-N), surgical/anesthetic effects (S6-N6), acute uremia (AU-S6), and regenerating liver (RL-S6) were: -17.3 (P less than 0.001), -4.0 (P = NS), -4.5 (P less than 0.05), and -1.0 g/24 h (P = NS), respectively. Changes in mean serum T4 (N, 5.3 +/- 1.3 micrograms/dl) were: -1.0 (P = NS), -0.6 (P = NS), -0.9 (P less than 0.05), and -1.0 micrograms/dl (P less than 0.05), respectively. Changes in mean serum T3 (N, 53 +/- 23 ng/dl) were: -8 (P = NS), -18 (P less than 0.05), -10 (P = NS), and -14 ng/dl (P less than 0.05), respectively. The NP and CB receptor pools of the AU and RL rats were not significantly different from those of age-matched N rats (NP, 25 +/- 5 fmol/mg DNA; CB, 405 +/- 134 fmol/mg DNA). Chronically uremic (CU) rats 2 weeks after five sixths nephrectomy (blood urea nitrogen, 36 +/- 2 mg/dl) did not exhibit significant change in their extractable receptor pools. Complete starvation for 24 h (NO) or 72 h (NOO) generally resulted in marked reductions in receptor concentrations compared to those in age-matched N rats fed ad libitum: NP pool (N, 31 +/- 17 fmol/mg DNA): NO-N, -40% (P = NS); NOO-N, -59% (P less than 0.01); CB pool (N, 303 +/- 105 fmol/mg DNA): NO-N, -19% (P less than 0.05); NOO-N, -41% (P less than 0.001). These studies indicate that severe AU, moderate CU, and LR have relatively little effect on solubilized rat liver nuclear receptor concentrations. In contrast, complete starvation is a potent depressant of both nuclear receptor pools. In the surgical models of AU and LR, postoperative fasting was the primary cause of weight loss.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The effects of postoperative factors on serum thyroid hormones and rat liver nuclear 3,5,3'-triiodothyronine receptor concentrations in surgical models of uremia and regenerating liver. 383 53

To assess the effect of starvation and to explore the potential interrelationship of starvation and thyroid status at the pretranslational level, we have analyzed by two-dimensional gel electrophoresis, the hepatic translational products of starved and fed euthyroid and hypothyroid rats. 5 d of starvation resulted in a statistically significant change in 27 of 240 products visualized, whereas hypothyroidism caused a change in 20, both in comparison with the fed euthyroid state. Of considerable interest was that 68% of all changing messenger (m)RNA sequences were common to the hypothyroid and starved groups and showed the same directional shift. Further, both starvation and hypothyroidism yielded comparable decreases in total hepatic cytoplasmic RNA content. Although it has been well established that the level of circulating triiodothyronine (T3) and the level of hepatic nuclear receptors fall in starvation, this reduction cannot account for the observed decrease of total hepatic RNA nor for all of the alterations in the concentrations of specific mRNA sequences. Thus, administration of T3 to starved animals in a dose designed to occupy all nuclear T3 receptors fails to prevent the fall in total RNA and the majority of starvation-induced changes in the level of mRNA sequences. Moreover, starvation of athyreotic animals results in a further decrease in total RNA and in a further change in the level of individual mRNA species. We conclude, therefore, that although the reduced levels of circulating T3 and the nuclear T3 receptors can contribute to the observed results of starvation, the starvation-induced changes are not exclusively mediated by this factor. The striking overlap in the genomic response between hypothyroid and starved animals raises the possibility that those biochemical mechanisms regulated at a pretranslational level by T3 are either not helpful or injurious to the starving animal. The reduction in circulating T3 and nuclear receptor sites together with T3-independent mechanisms initiated in the starved animal may constitute redundant processes designed to conserve energy and substrate in the nutritionally deprived organism.
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PMID:Starvation and hypothyroidism exert an overlapping influence on rat hepatic messenger RNA activity profiles. 687 45

In vivo, refeeding starved chickens stimulates transcription of the avian gene for malic enzyme in liver; in hepatocytes in culture, triiodothyronine (T3) and insulin stimulate transcription of this gene. In vivo, starvation, and in hepatocytes in culture, glucagon, medium-chain fatty acids (MCFA) and long-chain fatty acids (LCFA) inhibit transcription of the malic enzyme gene. We have defined a T3-response unit in the 5'-flanking DNA of the malic enzyme gene; it contains one major T3 response element and several minor ones; maximum responsiveness is dependent on the presence of all of these elements. LCFA probably act by inhibiting binding of T3 to its nuclear receptor. MCFA appear to act by a different mechanism. Inhibitory MCFA have chain lengths of six, seven or eight carbons; a common feature of other inhibitory compounds is that they can be metabolized to MCFA. Eight-carbon fatty acids with a hydroxyl on the 2- or 3-carbon are more potent inhibitors than octanoate, whereas 2-bromo-fatty acids and 2-hydroxy hexanoate are not inhibitory. In transfection experiments with a large variety of constructs derived from the malic enzyme 5'-flanking DNA, the ability of fatty acids to inhibit promoter function localizes to regions of DNA that contain T3REs. Promoter function of artificial T3REs also is inhibited by MCFA. Inhibition of promoter function using malic enzyme DNA is relatively constant in magnitude irrespective of the size of the T3 response. We postulate that MCFA directly regulates one of the functions of the T3 receptor.
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PMID:Nutritional and hormonal regulation of the gene for malic enzyme. 955 23

The hepatic CYP4A enzymes are important fatty acid and prostaglandin omega-hydroxylases that are highly inducible by fibric acid hypolipidemic agents and other peroxisome proliferators. Induction of the CYP4A enzymes by peroxisome proliferators is mediated through the nuclear peroxisome proliferator-activated receptor alpha (PPARalpha). Fatty acids have recently been identified as endogenous ligands of PPARalpha, and this receptor has been implicated in the regulation of lipid homeostasis. In the present report we characterized the induction of the hepatic CYP4A genes in rats during the altered lipid metabolism associated with starvation and diabetes. The mRNA levels of CYP4A1, CYP4A2, and CYP4A3 were induced 7-17-fold in the livers of fasted animals and 3-8-fold in the livers of diabetic animals. This was accompanied by corresponding changes in CYP4A protein levels and arachidonic and lauric acid omega-hydroxylase activity. Interestingly, feeding animals after the fasting period caused as much as an 80% suppression of CYP4A mRNA levels, whereas CYP4A protein levels and functional activity returned to control values. A second PPARalpha-responsive gene, acyl-CoA oxidase, was also induced in rat liver by diabetes and fasting. By using PPARalpha-deficient mice, we unambiguously demonstrated that PPARalpha is strictly required for hepatic CYP4A induction by starvation and diabetes. Similarly, induction of hepatic thiolase and bifunctional enzyme also required expression of PPARalpha. This represents the first evidence for the pathophysiologically induced activation of a nuclear receptor.
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PMID:Peroxisome proliferator-activated receptor alpha controls the hepatic CYP4A induction adaptive response to starvation and diabetes. 981 74

Cardiac energy metabolic shifts occur as a normal response to diverse physiologic and dietary conditions and as a component of the pathophysiologic processes which accompany cardiac hypertrophy, heart failure, and myocardial ischemia. The capacity to produce energy via the utilization of fats by the mammalian postnatal heart is controlled in part at the level of expression of nuclear genes encoding enzymes involved in mitochondrial fatty acid beta-oxidation (FAO). The principal transcriptional regulator of FAO enzyme genes is the peroxisome proliferator-activated receptor alpha (PPARalpha), a member of the ligand-activated nuclear receptor superfamily. Among the ligand activators of PPARalpha are long-chain fatty acids; therefore, increased uptake of fatty acid substrate into the cardiac myocyte induces a transcriptional response leading to increased expression of FAO enzymes. PPARalpha-mediated control of cardiac metabolic gene expression is activated during postnatal development, short-term starvation, and in response to exercise training. In contrast, certain pathophysiologic states, such as pressure overload-induced hypertrophy, result in deactivation of PPARalpha and subsequent dysregulation of FAO enzyme gene expression, which sets the stage for abnormalities in cardiac lipid homeostasis and energy production, some of which are influenced by gender. Thus, PPARalpha not only serves a critical role in normal cardiac metabolic homeostasis, but alterations in PPARalpha signaling likely contribute to the pathogenesis of a variety of disease states. PPARalpha as a ligand-activated transcription factor is a potential target for the development of new therapeutic strategies aimed at the prevention of pathologic cardiac remodeling.
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PMID:PPAR signaling in the control of cardiac energy metabolism. 1128 1

Peroxisome proliferator-activated receptor alpha(PPARalpha) is a member of the steroid/nuclear receptor superfamily that is intensively expressed in the kidney, but its physiologic function is unknown. In this study, PPARalpha-null mice were used to help clarify the function. Starved PPARalpha-null mice were found to secrete significantly more quantities of urine albumin than starved wild-type mice. Furthermore, the appearance of giant lysosomes, marked accumulation of albumin, and an impaired ability concerning albumin digestion were found only in proximal tubules of the starved PPARalpha-null mice. These abnormalities were probably derived from ATP insufficiency as a result of the starvation-induced decline of carbohydrate metabolism and a lack of PPARalpha-dependent fatty acid metabolism. It is interesting that these abnormalities disappeared when glucose was administered. Taken together, these findings demonstrate important functions of PPARalpha in the proximal tubules, the dynamic regulation of the protein-degradation system through maintenance of ATP homeostasis, and emphasize the importance of the fatty acid metabolism in renal physiology.
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PMID:Identification of functions of peroxisome proliferator-activated receptor alpha in proximal tubules. 1208 64

Apolipoprotein E (apoE) mediates the hepatic clearance of plasma lipoproteins, facilitates cholesterol efflux from macrophages and aids neuronal lipid transport. ApoE is expressed at high levels in hepatocytes, macrophages and astrocytes. In the present study, we identify nuclear and cytosolic pools of apoE in human fibroblasts. Fibroblast apoE mRNA and protein levels were up-regulated during staurosporine-induced apoptosis and this was correlated with increased caspase-3 activity and apoptotic morphological alterations. Because the transcription of apoE and specific pro-apoptotic genes is regulated by the nuclear receptor LXR (liver X receptor) alpha, we analysed LXRalpha mRNA expression by quantitative real-time PCR and found it to be increased before apoE mRNA induction. The expression of ABCA1 (ATP-binding cassette transporter A1) mRNA, which is also regulated by LXRalpha, was increased in parallel with apoE mRNA, indicating that LXRalpha probably promotes apoE and ABCA1 transcription during apoptosis. Fibroblast apoE levels were increased under conditions of serum-starvation-induced growth arrest and hyperoxia-induced senescence. In both cases, an increased nuclear apoE level was observed, particularly in cells that accumulated lipofuscin. Nuclear apoE was translocated to the cytosol when mitotic nuclear disassembly occurred and this was associated with an increase in total cellular apoE levels. ApoE amino acid sequence analysis indicated several potential sites for phosphorylation. In vivo studies, using 32P-labelling and immunoprecipitation, revealed that fibroblast apoE can be phosphorylated. These studies reveal novel associations and potential roles for apoE in fundamental cellular processes.
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PMID:Induction of fibroblast apolipoprotein E expression during apoptosis, starvation-induced growth arrest and mitosis. 1465 20


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