Calorigenic Effect of Diiodothyronines In the Rat (original) (raw)
Related papers
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.
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...
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.
3,5-Diiodo-L-thyronine powerfully reduces adiposity in rats by increasing the burning of fats
Faseb Journal, 2005
The effect of thyroid hormones on metabolism has long supported their potential as drugs to stimulate fat reduction, but the concomitant induction of a thyrotoxic state has greatly limited their use. Recent evidence suggests that 3,5-diiodo-L-thyronine (T 2 ), a naturally occurring iodothyronine, stimulates metabolic rate via mechanisms involving the mitochondrial apparatus. We examined whether this effect would result in reduced energy storage. Here, we show that T 2 administration to rats receiving a high-fat diet (HFD) reduces both adiposity and body weight gain without inducing thyrotoxicity. Rats receiving HFD + T 2 showed (when compared with rats receiving HFD alone) a 13% lower body weight, a 42% higher liver fatty acid oxidation rate, ~50% less fat mass, a complete disappearance of fat from the liver, and significant reductions in the serum triglyceride and cholesterol levels (-52% and -18%, respectively). Thyroid hormones and thyroid-stimulating hormone (TSH) serum levels were not influenced by T 2 administration. The biochemical mechanism underlying the effects of T 2 on liver metabolism involves the carnitine palmitoyl-transferase system and mitochondrial uncoupling. If the results hold true for humans, pharmacological administration of T 2 might serve to counteract the problems associated with overweight, such as accumulation of lipids in liver and serum, without inducing thyrotoxicity. However, the results reported here do not exclude deleterious effects of T 2 on a longer time scale as well as do not show that T 2 acts in the same way in humans.
Are the Effects of T 3 on Resting Metabolic Rate in Euthyroid Rats Entirely Caused by T 3 Itself?
Endocrinology, 2002
Because we previously reported that T 3 and 3,5-diiodo-Lthyronine (3,5-T 2 ) both increase resting metabolic rate (RMR), 3,5-T 2 could be another thyroidal regulator of energy metabolism. This effect of 3,5-T 2 is evident in rats made hypothyroid by propylthiouracil and iopanoic acid, not in normal euthyroid (N) rats. Possibly, under euthyroid conditions, active 3,5-T 2 may need to be formed intracellularly from a precursor such as T 3 . We tested this hypothesis by giving a single injection of T 3 to N rats and comparing the time course of the variations in RMR with those of the changes in the serum and hepatic levels of 3,5-T 2 . Acute injection had an evident effect on RMR, 25 h earlier, in N rats than in rats made hypothyroid by propylthiouracil and iopanoic acid, maximal values (؉40%) being reached in the former at 24 -26 h. In N rats, the simultaneous injection of actinomycin D with the T 3 inhibited the late part of the effect (after 24 h) more strongly than the early part (14 -24 h). In serum and liver, 3,5-T 2 levels were increased significantly at 12-24 h after T 3 injection into N rats, a time at which RMR was rising rapidly to peak. These results seem to indicate that when T 3 is injected into N animals, not all the effects on RMR are attributable to T 3 itself, the early effect presumably being largely because of its in vivo deiodination to 3,5-T 2 . Because the effects of T 3 and 3,5-T 2 are additive, in N rats, the two iodothyronines probably cooperate in vivo to determine the total metabolic rate.
Molecular and Cellular Endocrinology, 2011
Thyronamines T 0 AM and T 1 AM are naturally occurring decarboxylated thyroid hormone derivatives. Their in vivo administration induces effects opposite to those induced by thyroid hormone, including lowering of body temperature. Since the mitochondrial energy-transduction apparatus is known to be a potential target of thyroid hormone and its derivatives, we investigated the in vitro effects of T 0 AM and T 1 AM on the rates of O 2 consumption and H 2 O 2 release by rat liver mitochondria. Hypothyroid animals were used because of the low levels of endogenous thyronamines. We found that both compounds are able to reduce mitochondrial O 2 consumption and increase H 2 O 2 release. The observed changes could be explained by a partial block, operated by thyronamines, at a site located near the site of action of antimycin A. This hypothesis was confirmed by the observation that thyronamines reduced the activity of Complex III where the site of antimycin action is located. Because thyronamines exerted their effects at concentrations comparable to those found in hepatic tissue, it is conceivable that they can affect in vivo mitochondrial O 2 consumption and H 2 O 2 production acting as modulators of thyroid hormone action.
3,5-Diiodo-L-Thyronine Activates Brown Adipose Tissue Thermogenesis in Hypothyroid Rats
PLOS ONE, 2015
3,5-diiodo-l-thyronine (T2), a thyroid hormone derivative, is capable of increasing energy expenditure, as well as preventing high fat diet-induced overweight and related metabolic dysfunction. Most studies to date on T2 have been carried out on liver and skeletal muscle. Considering the role of brown adipose tissue (BAT) in energy and metabolic homeostasis, we explored whether T2 could activate BAT thermogenesis. Using euthyroid, hypothyroid, and T2-treated hypothyroid rats (all maintained at thermoneutrality) in morphological and functional studies, we found that hypothyroidism suppresses the maximal oxidative capacity of BAT and thermogenesis, as revealed by reduced mitochondrial content and respiration, enlarged cells and lipid droplets, and increased number of unilocular cells within the tissue. In vivo administration of T2 to hypothyroid rats activated BAT thermogenesis and increased the sympathetic innervation and vascularization of tissue. Likewise, T2 increased BAT oxidative capacity in vitro when added to BAT homogenates from hypothyroid rats. In vivo administration of T2 to hypothyroid rats enhanced mitochondrial respiration. Moreover, UCP1 seems to be a molecular determinant underlying the effect of T2 on mitochondrial thermogenesis. In fact, inhibition of mitochondrial respiration by GDP and its reactivation by fatty acids were greater in mitochondria from T2-treated hypothyroid rats than untreated hypothyroid rats. In vivo administration of T2 led to an increase in PGC-1α protein levels in nuclei (transient) and mitochondria (longer lasting), suggesting a coordinate effect of T2 in these organelles that ultimately promotes net activation of mitochondrial biogenesis and BAT thermogenesis. The effect of T2 on PGC-1α is similar to that elicited by triiodothyronine. As a whole, the data reported here indicate T2 is a thyroid hormone derivative able to activate BAT thermogenesis.
3-IODOTHYRONAMINE Metabolism and Metabolic Effects in Rat White Adipocytes
2011
3-Iodothyronamine (T 1 AM), produced from thyroid hormones (TH) through decarboxylation and deiodination, is a potent agonist of trace amine-associated receptor 1 (TAAR1), a G protein-coupled receptor belonging to the family of TAARs. In vivo T 1 AM induces functional effects opposite to those produced on a longer time scale by TH and might represent a novel branch of TH signaling. In this study, we investigated the action of T 1 AM on thyroid and determined its uptake and catabolism using FRTL5 cells. The expression of TAAR1 was determined by PCR and western blot in FRTL5 cells, and cAMP, iodide uptake, and glucose uptake were measured after incubation with increasing concentrations of T 1 AM for different times. T 1 AM and its catabolites thyronamine (T 0 AM), 3-iodothyroacetic acid (TA 1), and thyroacetic acid (TA 0) were analyzed in FRTL5 cells by HPLC coupled to tandem mass spectrometry. The product of amplification of TAAR1 gene and TAAR1 protein was demonstrated in FRTL5 cells. No persistent and dose-dependent response to T 1 AM was observed after treatment with increasing doses of this substance for different times in terms of cAMP production and iodide uptake. A slight inhibition of glucose uptake was observed in the presence of 100 mM T 1 AM after 60 and 120 min (28 and 32% respectively), but the effect disappeared after 18 h. T 1 AM was taken up by FRTL5 cells and catabolized to T 0 AM, TA 1 , and TA 0 confirming the presence of deiodinase and amine oxidase activity in thyroid. In conclusion, T 1 AM determined a slight inhibition of glucose uptake in FRTL5 cells, but it was taken up and catabolized by these cells.
Journal of Experimental Biology, 2009
SUMMARYWe compared the changes in tissue aerobic metabolism and oxidative damage elicited by hypothyroid rat treatment with T3 and its analog GC-1. Aerobic capacities, evaluated by cytochrome oxidase activities, were increased more by T3 than by GC-1. Furthermore, the response of the tissues to T3 was similar, whereas the response to GC-1 was high in liver,low in muscle and scarce in heart. Both treatments induced increases in ADP-stimulated O2 consumption, which were consistent with those in aerobic capacities. However, unlike T3, GC-1 differentially affected pyruvate/malate- and succinate-supported respiration, suggesting that respiratory chain components do not respond as a unit to GC-1 stimulation. According to the positive relationship between electron carrier levels and rates of mitochondrial generation of oxidative species, the most extensive damage to lipids and proteins was found in T3-treated rats. Examination of antioxidant enzyme activities and scavenger levels did not c...