Catabolic effects of thyroid hormone excess: The contribution of adrenergic activity to hypermetabolism and protein breakdown (original) (raw)
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Metabolic effects of 3,5-Diiodo-L-Thyronine
Bollettino della Società italiana di biologia sperimentale, 2021
Thyroid hormones have been proposed as anti obesity drugs due to their effects on basal metabolism and the ability to increase energy expenditure. However, their clinical use has been strongly curbed by the concomitant onset of thyrotoxicosis. In this setting, several studies have been undertaken to assess the role of 3,5 diiodo-L-thyronine (T2), an endogenous metabolite of thyroid hormone derived from the enzymatic deiodination of triodothyronine T3. The metabolic effects of T2 are similar to those induced by T3. However, these effects appear to involve different and not welldefined mechanisms that make this molecule clinically useful as potential drug in the treatment of pathological conditions such as obesity and hepatic steatosis. The main pharmacological target of T2 appears to be the mitochondria. Therefore, the administration of T2 to obese subjects might improve the mitochondrial performance, which is generally recognized to be reduced in these subjects who must oxidize grea...
Effect of thyroid status on α- and β-catecholamine responsiveness of hamster adipocytes
Biochimica et Biophysica Acta (BBA) - General Subjects, 1981
It has been suggested that part of the increased/3-catecholamine responsiveness in hyperthyroid animals is due to a decrease in a-catecholamine action. The present results indicate that neither hyperthyroidism nor hypothyroidism altered the a2-adrenergic inhibition of adenylate cyclase or the a~-adrenergic stimulation of phosphatidylinositol turnover in adipocytes from the white adipose tissue of hamsters. No effect of hyperthyroidism was found on the Kcl for binding of [3H]dihydroergocryptine or the number of binding sites in membranes prepared from hamster adipocyte tissue. The stimulation of cyclic AMP due to ~-catecholamines was enhanced in adipocytes from hyperthyroid hamsters, as was lipolysis. However, in adipocytes from hyperthyroid hamsters the maximal stimulation of cyclic AMP due to isoproterenol, ACTH or epinephrine plus yohimbine, as seen in the presence of adenosine deaminase and theophylline, was less than in adipocytes from euthyroid hamsters. The activation of adenylate cyclase by isoproterenol was the same in membranes from hyperthyroid as compared to those from euthyroid hamsters in the absence or presence of guanine nucleotides. These data suggest that thyroid status has little effect on a-catecholamine action but enhances the activation of lipolysis by ~-catecholamine agonists.
1997
1. Although the first evidence of a relationship between the thyroid and metabolism was reported in 1895, the mechanism by which thyroid hormones influence resting metabolic rate in whole animals is still poorly understood. This paper reports an attempt to test whether diiodothyronines (T2s) and triiodothyronine (T3) have different roles in the control of resting metabolism (RM). 2. Changes in resting metabolic rate were measured in hypothyroid rats treated acutely (25 ,ug (100 g body weight)-) either with one of the T2s or with T3. Injection of T3 induced an increase of about 35% in RM that started 25-30 h after the injection and lasted until 5-6 days after the injection, the maximal value being observed at 50-75 h. The injection of Ts evoked a temporally different pattern of response. The increases in RM started 6-12 h after the injection, had almost disappeared after 48 h, and the maximal stimulation was observed at 28-30 h. 3. When actinomycin D (an inhibitor of protein synthesis) and T3 were given together, the stimulation of RM was almost completely abolished. The simultaneous injection of actinomycin D and either of the T s, on the other hand, did not cause any attenuation of the stimulation seen with the T2 s alone. 4. Following chronic treatment (3 weeks) with either T3 or T2s there was a stimulation of organ growth only after the administration of T3. 5. Chronic administration of either T2s or T3 to hypothyroid rats significantly enhanced the oxidative capacity of each of the tissues considered. In the case of T2s the stimulation was almost the same whether it was expressed as an increase in specific activity or total tissue activity. In the case of T3 the increases were, in the main, secondary to the hypertrophic or hyperplastic effect. 6. These results indicate that T2s and T3 exert different effects on RM. The effects of T2s are rapid and possibly mediated by their direct interaction with mitochondria. Those of T3 are slower and more prolonged, and at least partly attributable to a modulation of the cellularity of tissues that are metabolically very active.
Impaired Thyroid Function in Metabolic Disorders
Emerging Contaminants and Associated Treatment Technologies
The tri-iodothyronine (T3) and thyroxine (T4) are the two important thyroid hormones through which endocrine system controls the cellular and intracellular functions of body. In response to certain stimuli, the hypothalamic thyrotropin-releasing hormone (TRH) governs the release of thyroid stimulating hormone (TSH) from anterior pituitary. The thyroid hormones are synthesised by the action of TSH on membrane receptors of thyroid cell follicle and regulated by negative feedback effect of circulating T3 and T4 on anterior pituitary. Thyroid hormones play their important role in growth, development and regulation of metabolism in body. Alterations in normal regulation mechanisms of body in certain metabolic disorders result in impaired thyroid function. Diminished thyroid activity due to decreased production of thyroid hormones or tissue resistance is termed as hypothyroidism. While hyperthyroidism is characterised by overactive thyroid glands leading to increased production and secretion of thyroid hormones. Which may result in a subsequent increase in metabolic rate of body. On the other hand, impaired thyroid function may also result in metabolic abnormalities. Increased level of leptin hormones in obesity results in increased secretion of TRH and TSH
Endocrinology, 2004
Hyperthyroidism and states of adrenergic hyperactivity have many common clinical features, suggesting similar pathogenic mechanisms of action. The widespread use of adrenergic receptor (AR) antagonists (-blockers) to treat hyperthyroidism has led to the belief that the physiological consequences of thyroid hormone (TH) excess are mediated in part via catecholamine signaling through ARs. To test this hypothesis, we compared the response to TH excess in mice lacking the three known ARs (-less) vs. wild-type (WT) mice. Although -less mice had a lower heart rate at baseline in comparison to WT mice, the metabolic and cardiovascular responses to hyperthyroidism were equivalent in both WT and -less mice. These data indicate that the metabolic and cardiovascular effects of TH excess are largely independent of ARs. These findings suggest that the efficacy of clinical treatment of hyperthyroidism with -blockers is due to antagonism of sympathetic signaling, and that this process functions independently of TH action.
Metabolic effects of 3,5 Diiodo L Thyronine Giammanco M et al
Journal of Biological Research, 2020
Thyroid hormones have been proposed as anti obesity drugs due to their effects on basal metabolism and the ability to increase energy expenditure. However, their clinical use has been strongly curbed by the concomitant onset of thyrotoxicosis. In this setting, several studies have been undertaken to assess the role of 3,5 diio-do-L-thyronine (T2), an endogenous metabolite of thyroid hormone derived from the enzymatic deiodination of triodothyronine T3. The metabolic effects of T2 are similar to those induced by T3. However, these effects appear to involve different and not well-defined mechanisms that make this molecule clinically useful as potential drug in the treatment of pathological conditions such as obesity and hepatic steatosis. The main pharmacological target of T2 appears to be the mitochondria. Therefore, the administration of T2 to obese subjects might improve the mitochondrial performance, which is generally recognized to be reduced in these subjects who must oxidize greater quantities of substrates. In this context, it can be hypothesized that T2, by acting mainly on mitochondrial function and oxidative stress, might be able to prevent and revert the tissue damages and hepatic steatosis induced by a hyperlipidic diet and a concomitant reduction in the circulating levels LDL and triglyc-erides as well. This review the discuss the mechanisms of action of T2 and the possible, future clinical uses of T2 analogs for the treatment lipid dysmetabolism related to obesity and overweight.
Thyroid hormone metabolism in obesity
International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity, 2000
Serum thyroid hormone concentrations and their metabolic fate are within the normal range limits in obese subjects. Also serum TSH concentrations and its response to TRH are normal, suggesting that tissue availability of thyroid hormones is normally preserved in these subjects. In contrast, during caloric restriction serum T3 concentrations decrease as a consequence of its reduced production rate from peripheral deiodination of T4. Opposite, serum rT3 concentrations markedly increase as a result of its decreased metabolic clearance rate. During caloric overfeeding serum T3 concentration increase whereas serum rT3 concentrations decrease. In this condition the production rate of T3 increases. During caloric restriction and overfeeding serum T4 concentrations and its production and degradation are not modified.
Acta Diabetologica Latina, 1984
Four decades ago, HOUSSAY ~ showed that the administration of thyroid powder to animals of different species initially brought about a temporary condition of diabetes which Houssay termed 'thyroid diabetes', and which was reversible, regardless of whether thyroid treatment was continued or withdrawn. However, if thyroid was given to animals with preexisting pancreatic injury, the condition was no longer reversible and a permaaaent diabetes 'meta~hyroid' or 'Houssay' diabetes ensued. More recently, L~:NOUETTE et at. t-~ demonstrated that in the later stages of spontaneous human hyperthyroidism, blood glucose level, insulinemia and ~-adrenergic tone are high and suggested chat in the early" stages of hyper~yroidism metabolic changes resembling those of latent diabetes, with relative insulin deficiency are observable. Recently, groups of patients with hyperthyroidism of recent onset have been reported to react to glucose injection with hardly any insulin secretionL On the other hand, many scientific reports in the literature show that hyperthyroidism enhances the acdon of epinephrine on tissues regardless of the stage of thyroid hyperfunction which, as we already "know, evolves in two completely opposke stages. We were therefore interested in studying the
Standard hypothyroid treatment did not restore proper metabolic response to carbohydrate
Endocrine
Purpose Hypothyroidism is associated with a lower metabolic rate, impaired glucose tolerance, and increased responsiveness of sympathetic nervous system to glucose ingestion. The Levothyroxine (LT4) monotherapy is the standard treatment for hypothyroidism; however to what extent this treatment restores the patients’ metabolism has not been verified. The aim of this study was to test the hypothesis that standard LT4 therapy may not restore proper metabolic response to carbohydrate ingestion. Methods Energy expenditure, glucose tolerance, and catecholamine response to glucose ingestion were compared in 18 subjects with pharmacologically compensated hypothyroidism (PCH) and controls, at baseline and during oral glucose tolerance test conditions. Results Metabolic rate was significantly lower in PCH (P