scholarly journals Early induction of hepatic deiodinase type 1 inhibits hepatosteatosis during NAFLD progression

2021 ◽  
Author(s):  
Eveline Bruinstroop ◽  
Jin Zhou ◽  
Madhulika Tripathi ◽  
Winifred Yau ◽  
Anita Boelen ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Hormone Treatment ◽  
Compensatory Mechanisms ◽  
Deficient Diet ◽  
Alcoholic Fatty Liver ◽  
Thyroid Hormone Metabolism ◽  
Hepatic Cells ◽  
Triglyceride Content

Objective - Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum ranging from hepatosteatosis to progressive non-alcoholic steatohepatitis that can lead to cirrhosis. Humans with low levels of the prohormone thyroxine (T4) have a higher incidence of NAFLD and thyroid hormone treatment is very promising in all patients with NAFLD. Deiodinase 1 (Dio1) is a hepatic enzyme that converts T4 to the bioactive T3, and therefore regulates intracellular thyroid hormone availability in the liver. The role of this intracellular regulation was investigated during the progression of NAFLD. Methods - We investigated intracellular thyroid hormone metabolism in two NAFLD models: wild-type mice fed Western diet with fructose and Leprdb mice fed a methionine- and choline-deficient diet. AAV8-mediated liver-specific Dio1 knockdown was employed to investigate the role of Dio1 during the progression of NAFLD. Intrahepatic thyroid hormone levels, deiodinase activity and metabolic parameters were measured. Results - Dio1 expression and activity were increased in the early stages of NAFLD and were associated with an increased T3/T4 ratio. Prevention of this increase by AAV8-mediated liver-specific Dio1 knockdown increased hepatic triglycerides and cholesterol as well as decreased pACC/ACC ratio and acylcarnitine levels suggesting there was lower β-oxidation. Dio1 siRNA KD in hepatic cells treated with fatty acids showed increased lipid accumulation and decreased oxidative phosphorylation. Conclusion - Hepatic Dio1 gene expression was modulated by dietary conditions, increased during hepatosteatosis and early NASH, and regulated hepatic triglyceride content. These early adaptations likely represent compensatory mechanisms to reduce hepatosteatosis and prevent NASH progression.

scholarly journals Lacking thyroid hormone receptor β gene does not influence alterations in peripheral thyroid hormone metabolism during acute illness

2008 ◽  
Vol 197 (1) ◽  
pp. 151-158 ◽  
Author(s):  
J Kwakkel ◽  
O Chassande ◽  
H C van Beeren ◽  
W M Wiersinga ◽  
A Boelen
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Hormone Metabolism ◽  
Thyroid Hormone Metabolism ◽  
Males And Females ◽  
Induced Changes ◽  
Thyroid Hormone Receptor Β

The downregulation of liver deiodinase type 1 (D1) is supposed to be one of the mechanisms behind the decrease in serum tri-iodothyronine (T3) observed during non-thyroidal illness (NTI). Liver D1 mRNA expression is positively regulated by T3, mainly via the thyroid hormone receptor (TR)β1. One might thus expect that lacking the TRβ gene would result in diminished downregulation of liver D1 expression and a smaller decrease in serum T3 during illness. In this study, we used TRβ−/− mice to evaluate the role of TRβ in lipopolysaccharide (LPS, a bacterial endotoxin)-induced changes in thyroid hormone metabolism. Our results show that the LPS-induced serum T3 and thyroxine and liver D1 decrease takes place despite the absence of TRβ. Furthermore, we observed basal differences in liver D1 mRNA and activity between TRβ−/− and wild-type mice and TRβ−/− males and females, which did not result in differences in serum T3. Serum T3 decreased rapidly after LPS administration, followed by decreased liver D1, indicating that the contribution of liver D1 during NTI may be limited with respect to decreased serum T3 levels. Muscle D2 mRNA did not compensate for the low basal liver D1 observed in TRβ−/− mice and increased in response to LPS in TRβ−/− and WT mice. Other (TRβ independent) mechanisms like decreased thyroidal secretion and decreased binding to thyroid hormone-binding proteins probably play a role in the early decrease in serum T3 observed in this study.

Neutralization of TNF does not influence endotoxininduced changes in thyroid hormone metabolism in humans

1999 ◽  
Vol 276 (2) ◽  
pp. R357-R362 ◽  
Author(s):  
Tom van der Poll ◽  
Erik Endert ◽  
Susette M. Coyle ◽  
Jan M. Agosti ◽  
Stephen F. Lowry
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Stimulating Hormone ◽  
Hormone Metabolism ◽  
Thyroid Hormone Metabolism ◽  
Healthy Humans ◽  
Transient Rise ◽  
Induced Changes ◽  
Necrosis Factor ◽  
Control Study

To determine the role of tumor necrosis factor (TNF) in endotoxin-induced changes in plasma thyroid hormone and thyroid-stimulating hormone (TSH) concentrations, 24 healthy postabsorptive humans were studied on a control study day ( n= 6), after infusion of a recombinant TNF receptor IgG fusion protein (TNFR:Fc; 6 mg/m2; n = 6) after intravenous injection of endotoxin (2 ng/kg; n = 6), or after administration of endotoxin with TNFR:Fc ( n = 6). Administration of TNFR:Fc alone did not affect thyroid hormone or TSH levels when compared with the control day. Endotoxin induced a transient rise in plasma TNF activity (1.5 h: 219 ± 42 pg/ml), which was completely prevented by TNFR:Fc ( P < 0.05). After endotoxin administration, plasmal-thyroxine (T4), free T4, 3,5,3′-triiodothyronine (T3), and TSH were lower and 3,3′,5′-triiodothyronine was higher than on the control day (all P < 0.05). Coinfusion of TNFR:Fc with endotoxin did not influence these endotoxin-induced changes. Our results suggest that endogenous TNF does not play an important role in the alterations in plasma thyroid hormone and TSH concentrations induced by mild endotoxemia in healthy humans.

Effects of marginal iodine deficiency during pregnancy: iodide uptake by the maternal and fetal thyroid

1997 ◽  
Vol 273 (6) ◽  
pp. E1121-E1126 ◽  
Author(s):  
P. M. Versloot ◽  
J. P. Schröder-Van Der Elst ◽  
D. Van Der Heide ◽  
L. Boogerd
Keyword(s):  
Thyroid Hormone ◽  
Iodine Deficiency ◽  
Specific Activity ◽  
Hormone Production ◽  
Iodide Uptake ◽  
Deficient Diet ◽  
Pregnant Rats ◽  
Thyroid Hormone Metabolism ◽  
Fetal Thyroid ◽  
The Absolute

Iodide uptake by the thyroid is an active process. Iodine deficiency and pregnancy are known to influence thyroid hormone metabolism. The aim of this study was to clarify the effects of iodine deficiency and pregnancy on iodide uptake by the thyroid. Radioiodide was injected intravenously into nonpregnant and 19-day pregnant rats receiving a normal or marginally iodine-deficient diet. The uptake of radioiodide by the thyroid was measured continuously for 4 h. The absolute iodide uptake by the maternal and fetal thyroid glands at 24 h was calculated by means of the urinary specific activity. Pregnancy resulted in a decrease in the absolute thyroidal iodide uptake. Marginal iodine deficiency had no effect on the absolute iodide uptake by the maternal thyroid. The decreased plasma inorganic iodide was compensated by an increase in thyroidal clearance. A similar compensation was not found for the fetus; the uptake of iodide by the fetal thyroid decreased by 50% during marginal iodine deficiency. This can lead to diminished thyroid hormone production, which will have a negative effect on fetal development, especially of the brain.

The role of selenium in thyroid hormone metabolism

1991 ◽  
Vol 69 (11) ◽  
pp. 1648-1652 ◽  
Author(s):  
John R. Arthur
Keyword(s):  
Thyroid Hormone ◽  
Iodine Deficiency ◽  
Selenium Deficiency ◽  
Major Influence ◽  
Type I ◽  
Hormone Metabolism ◽  
Thyroid Hormone Metabolism ◽  
Iodothyronine Deiodinases ◽  
Clinical Changes

In animals, decreases in selenium-containing glutathione peroxidase activity and the resultant impairment of peroxide metabolism can account for many, but not all of the biochemical and clinical changes caused by selenium deficiency. Recently, however, type I iodothyronine 5′-deiodinase has also been shown to be a selenium-containing enzyme. This explains the impairment of thyroid hormone metabolism caused by selenium deficiency in animals with a normal vitamin E status. Since iodothyronine 5′-deiodinases are essential for the production of the active thyroid hormone 3,5,3′-triiodothyronine, some of the consequences of selenium deficiency may result from thyroid changes rather than inability to metabolise peroxides. In particular, the impaired thyroid hormone metabolism may be responsible for decreased growth and resistance to cold stress in selenium-deficient animals. A further consequence of the role of selenium in thyroid hormone metabolism is the exacerbation of some of the thyroid changes in iodine deficiency by a concurrent selenium deficiency. Selenium status may therefore have a major influence on the outcome of iodine deficiency in both human and animal populations.Key words: selenium, thyroid hormones, iodothyronine deiodinases, iodine, nutritional disorders.

scholarly journals The Role of Rho Kinase in Sex-Dependent Vascular Dysfunction in Type 1 Diabetes

2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
Author(s):  
Daniel W. Nuno ◽  
Kathryn G. Lamping
Keyword(s):  
Kinase Inhibitors ◽  
Vascular Dysfunction ◽  
Rho Kinase ◽  
Term Treatment ◽  
Compensatory Mechanisms ◽  
Rho Kinase Inhibitors ◽  
Long Term Treatment

We hypothesized that rho/rho kinase plays a role in sex differences in vascular dysfunction of diabetics. Contractions to serotonin were greater in isolated aortic rings from nondiabetic males versus females and increased further in streptozotocin-induced diabetic males but not females. The increased contractions to serotonin in males were reduced by inhibitors of rho kinase (fasudil, Y27632 and H1152) despite no change in expression of rhoA or rho kinase. Contractions to U46619 were not altered by fasudil or Y27632 or the presence of diabetes. In contrast to acute effects of fasudil, chronic treatment with fasudil increased contractions to serotonin in aorta from both non-diabetic and diabetic males. In summary, serotonin-induced contractions were increased in aorta from diabetic males but not females. Although administration of rho kinase inhibitors acutely decreased contractions to serotonin, long-term treatment with fasudil increased contractions. Long-term fasudil treatment may increase compensatory mechanisms to enhance vasoconstrictions.

scholarly journals Selenium influences growth via thyroid hormone status in broiler chickens

2000 ◽  
Vol 84 (5) ◽  
pp. 727-732 ◽  
Author(s):  
He Jianhua ◽  
Akira Ohtsuka ◽  
Kunioki Hayashi
Keyword(s):  
Skeletal Muscle ◽  
Thyroid Hormone ◽  
Broiler Chickens ◽  
Muscle Protein ◽  
Skeletal Muscle Protein ◽  
Hormone Metabolism ◽  
Deficient Diet ◽  
Thyroid Hormone Metabolism ◽  
Iopanoic Acid ◽  
Hormone Status

As there is a possibility that Se influences the growth of animals via thyroid hormone metabolism, the following three experiments were undertaken in order to determine the effects of dietary Se on growth, skeletal muscle protein turnover and thyroid hormone status in broiler chickens. Broiler chickens were raised on a Se-deficient diet until 12 d of age and then used for the experiments. In Experiment 1, twenty-eight birds were randomly assigned to four groups and fed purified diets with the following amounts of Se supplementation: 0·0, 0·1, 0·3 and 0·5 mg Se/kg diet. Dietary Se supplementation significantly increased plasma 3,5,3′-triiodothyronine (T3) concentration and improved growth, while plasma thyroxine (T4) concentration was decreased. In Experiment 2, twenty-eight birds were assigned to four groups and fed either a Se-deficient diet or a Se-supplemented diet (0·3 mg Se/kg diet) with or without the supplementation of iopanoic acid, a specific inhibitor of 5′-deiodinase (5 mg/kg diet). The growth was promoted and feed efficiency was improved by dietary Se supplementation as was also observed in Experiment 1. However, this effect of Se was halted by iopanoic acid supplementation. Hepatic 5′-deiodinase activity was elevated by Se and inhibited by iopanoic acid. In Experiment 3, birds were fed on the following diets to show that Se influences growth of birds via thyroid hormone metabolism: Se-deficient diet, Se-supplemented diets (0·1 and 0·3 mg/kg) and T3 supplemented diets (0·1 and 0·3 mg/kg diet). Lower dietary T3 supplementation (0·1 mg/kg diet) resulted in growth promotion similar to Se supplementation, while higher level of T3 caused growth depression. Furthermore, it was observed that the rate of skeletal muscle protein breakdown tended to be increased by Se similarly to the effect of T3. In conclusion, it was shown in the present study that Se deficiency depresses growth of broilers by inhibiting hepatic 5′-deiodinase activity which causes lower plasma T3 concentration.

Hashimoto's Encephalopathy

2020 ◽  
pp. 126-140
Keyword(s):  
Thyroid Hormone ◽  
Oral Prednisone ◽  
Hormone Treatment ◽  
High Dose ◽  
Thyroid Antibodies ◽  
Depression And Anxiety ◽  
Hashimoto’S Encephalopathy ◽  
Methyl Prednisolone ◽  
Neuro Inflammation

Hashimoto's encephalopathy is a relapsing encephalopathy occurring in association with Hashimoto's thyroiditis (HT) with high titers of anti-thyroid antibodies. The mechanism of pathogenesis is unknown. Auto-antibodies to α-enolase have been found to be associated with Hashimoto's encephalopathy. Recently, the crucial role of neuro-inflammation in the development of psychological disorders including depression and anxiety has received more attention. Because the majority of patients with Hashimoto's encephalopathy respond to steroids or immuno-suppressant treatment, this condition is now also referred to as “steroid-responsive encephalopathy.” Initial treatment is usually with oral prednisone (50–150 mg/day) or high-dose IV methyl-Prednisolone (1 g/day) for 3-7 days. Thyroid hormone treatment is also included if required. This chapter explores Hashimoto's encephalopathy.

The role of dietary fat in peripheral thyroid hormone metabolism

Metabolism ◽  
1980 ◽  
Vol 29 (10) ◽  
pp. 930-935 ◽  
Author(s):  
M.H. Otten ◽  
G. Hennemann ◽  
R. Docter ◽  
T.J. Visser
Keyword(s):  
Thyroid Hormone ◽  
Dietary Fat ◽  
Hormone Metabolism ◽  
Thyroid Hormone Metabolism

scholarly journals Type 1 deiodinase is stimulated by iodothyronines and involved in thyroid hormone metabolism in human somatomammotroph GX cells

1999 ◽  
pp. 367-370 ◽  
Author(s):  
A Baur ◽  
J Kohrle
Keyword(s):  
Thyroid Hormone ◽  
Anterior Pituitary ◽  
Specific Activity ◽  
Thyroid Hormone Metabolism ◽  
Phenolic Ring ◽  
Liver Membranes ◽  
Significant Release ◽  
Hormone Inactivation ◽  
Serum Free Conditions

BACKGROUND: Local 5'-deiOdination of l-thyroxine (T4) to the active thyroid hormone, 3,3',5-tri-iodothyronine (T3) via two deiodinase isoenzymes (D1 and D2) has an important role for various T3-dependent functions in the anterior pituitary. However, no evidence has been presented yet for thyroid hormone inactivation via the 5-deiodinase (D3) in anterior pituitary models. METHODS: Using the human somatomammotroph cell line, GX, we analysed effects of T3 and its 5'-deiodination product, 3,5-di-iodothyronine (3,5-T2), on deiodinase activities, measuring release of iodide-125 (125I-) from phenolic-ring- or tyrosyl-ring-labelled substrates respectively. RESULTS: T3 and 3,5-T2 rapidly stimulated D1 activity in GX cells in the presence of serum in the culture medium, whereas D2 activity was not detectable under these conditions. However, when the cells were kept under serum-free conditions, specific activity of D2 reached levels similar to those of D1. With tyrosyl-ring labelled 3, 5-[125I]-,3'-T3 as substrate, a significant release of 125I- was observed in GX cell homogenates. This is comparable to the D1 activity of liver membranes, which preferentially catalyses 5'-deiodination, but to some extent also 5-deiodination, at the tyrosyl ring. CONCLUSIONS: D1 activity of human GX cells is increased by T3 and 3,5-T2. Inactivation of T3 in the anterior pituitary might occur by deiodination at the tyrosyl ring via D1, thus terminating the stimulatory thyroid hormone signal in human somatomammotroph cells.

THE ROLE OF THYRONINE IN THYROID HORMONE METABOLISM

1979 ◽  
Vol 49 (4) ◽  
pp. 658-660 ◽  
Author(s):  
P. WILLETTS ◽  
D.N. CROSSLEY ◽  
D.B. RAMSDEN ◽  
R. HOFFENBERG
Keyword(s):  
Thyroid Hormone ◽  
Hormone Metabolism ◽  
Thyroid Hormone Metabolism
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