1,721,222 research outputs found
THYROID HORMONE AND UNCOUPLING PROTEINS.
No full textThyroid hormone (TH/T3) exerts many of its effects on energy metabolism by affecting gene transcription. However, although this is an important target for T3, only a limited number of T3-responsive genes have been identified and studied. Among these, the genes for uncoupling proteins (UCPs) have attracted the interest of scientists. Although the role of UCP1 seems quite well established, uncertainty surrounds the physiological function of the recently discovered UCP1 analogs, UCP2 and UCP3. The literature suggests that T3 affects both the expression and the activity of each of these UCPs but further studies are needed to establish whether the mechanisms activated by the hormone are the same. Recently, because of their larger range of expression, much attention has been devoted to UCP2 and UCP3. Most detailed studies on the involvement of these proteins as mediators of the effects of T3 on metabolism have focused on UCP3 because of its expression in skeletal muscle. T3 seems to be unique in having the ability to stimulate the expression and activity of UCP3 and this may be related to the capacity of T3 to activate the integrated biochemical processes linked to UCP activity, such as those related to fatty acids, coenzyme Q and free radicals. © 2003 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved
Thyroid hormones and mitochondria
No full textBecause of their central role in the regulation of energy-transduction, mitochondria, the major site of oxidative processes within the cell, are considered a likely subcellular target for the action that thyroid hormones exert on energy metabolism. However, the mechanism underlying the regulation of basal metabolic rate (BMR) by thyroid hormones still remains unclear. It has been suggested that these hormones might uncouple substrate oxidation from ATP synthesis, but there are no clear-cut data to support this idea. Two iodothyronines have been identified as effectors of the actions of thyroid hormones on energy metabolism: 3′,3,5-triiodo-L-thyronine (T3) and 3,5-diiodo-L-thyronine (T2). Both have significant effects on BMR, but their mechanisms of action are not identical. T3 acts on the nucleus to influence the expression of genes involved in the regulation of cellular metabolism and mitochondria function; 3,5-T2, on the other hand, acts by directly influencing the mitochondrial energy-transduction apparatus. A molecular determinant of the effects of T3 could be uncoupling protein-3 (UCP-3), while the cytochrome-c oxidase complex is a possible target for 3,5-T2. In conclusion, it is likely that iodothyronines regulate energy metabolism by both short-term and long-term mechanisms, and that they act in more than one way in affecting mitochondrial functions
Interaction of diiodothyronines with isolated cytochromec oxidase
No full textAbstractDiiodothyronines (3,3′-T2 and 3,5-T2) stimulate the activity of isolated cytochromec oxidase (COX) from bovine heart mitochondria. Maximal stimulation of activity (about 50%) is obtained with 3,3′-T2 at pH 6.4 and with 3,5-T2 at pH 7.4. In contrast, 3,5,3′-triiodothyronine (T3) exhibited no or little stimulation of COX activity. Binding of the hormones to COX leads to conformational changes as shown by modified visible spectra of the oxidized enzyme. It is suggested that ‘short-term’ effects of thyroid hormones on mitochondrial respiration are at least partly due to the allosteric interaction of diiodothyronines with the COX complex
Effect of 3,5-diiodo-L-thyronine on thyroid stimulating hormone and growth hormone serum levels in hypothyroid rats.
No full textWe have investigated the biological effects of physiological doses of 3,5-diiodo-L-thyronine (3,5-T2) and 3,3'-diiodo-L-thyronine (3,3'-T2) (at doses from 2.5 to 10 μg/100 g BW) on serum TSH and GH levels in rats made hypothyroid by propylthiouracil and iopanoic acid administration. In such animals deiodinase activities were inhibited and thyroid hormones serum levels strongly reduced. The effects of T2s were compared with those elicited by 3,5,3'-triiodo-L-thyronine (T3) (2.5 μg/100 g BW). The serum TSH level was much greater in hypothyroid rats than in euthyroid ones. T3 administration suppressed TSH by 88% compared to control (i.e, the level in hypothyroid rats); it thus reached a value not significantly different from that seen in the euthyroid rats. 3,5-T2 produced a similar effect, suppressing the TSH level by about 75% compared to control; it thus reached values not significantly different from those of the euthyroid and T3treated rats. By contrast, 3,3'-T2 had no effect on TSH, whatever the dose. The serum GH level was much lower in hypothyroid rats than in euthyroid ones. T3 administration increased the GH level by about 5-fold, restoring it to the value seen in euthyroid rats. 3,5-T2-treated hypothyroid rats, at all the doses used (from 2.5 to 10 μg/100 g Bw), showed increased serum GH levels: at a dose of 10 μg/100 g BW the level reached a value about 5-fold higher than that in hypothyroid rats. This value was not significantly different from those of euthyroid and T3-treated rats. 3,3'-T2 did not affect GH levels whatever the dose. Thus, 3,5-T2 (but not 3,3'-T2) seems to mimic the effects of T3 on serum TSH and GH levels in rats
FASTING, LIPID METABOLISM AND TRIIODOTHYRONINE IN RAT GASTROCNEMIUS MUSCLE: INTERRELATED ROLES OF UNCOUPLING PROTEIN 3, MITOCHONDRIAL THIOESTERASE AND COENZYME Q.
No full textEffect of 3,5-diiodo-L-thyronine on the mitochondrial energy trasduction apparatus
No full textWe examined the effect of a single injection of 3,5-di-iodo-L-thyronine (3,5-T2) (150 microg/100 g body weight) on the rat liver mitochondrial energy-transduction apparatus. We applied 'top-down' elasticity analysis, which allows identification of the site of action of an effector within a metabolic pathway. This kinetic approach considers oxidative phosphorylation as two blocks of reactions: those generating the mitochondrial inner-membrane potential (DeltaPsi; 'substrate oxidation') and those 'consuming' it ('proton leak' and 'phosphorylating system'). The results show that 1 h after the injection of 3,5-T2, state 4 (respiratory state in which there is no ATP synthesis and the exogenous ADP added has been exhausted) and state 3 (respiratory state in which ATP synthesis is at maximal rate) of mitochondrial respiration were significantly increased (by approx. 30%). 'Top-down' elasticity analysis revealed that these increases were due to the stimulation of reactions involved in substrate oxidation; neither 'proton leak' nor the 'phosphorylating system' was influenced by 3,5-T2. Using the same approach we divided the respiratory chain into two blocks of reactions: cytochrome c reducers and cytochrome c oxidizers. We found that both cytochrome c reducers and cytochrome c oxidizers are targets for 3,5-T2. The rapidity with which 3,5-T2 acts in stimulating the mitochondrial respiration rate suggests to us that di-iodo-L-thyronine may play an important role in the physiological conditions in which rapid energy utilization is required, such as cold exposure or overfeeding
Thyroid hormones and mitochondria: With a brief look at derivatives and analogues
No full textThyroid hormones (TH) have a multiplicity of effects. Early in life, they mainly affect development and differentiation, while later on they have particularly important influences over metabolic processes in almost all tissues. It is now quite widely accepted that thyroid hormones have two types of effects on mitochondria. The first is a rapid stimulation of respiration, which is evident within minutes/hours after hormone treatment, and it is probable that extranuclear/non-genomic mechanisms underlie this effect. The second response occurs one to several days after hormone treatment, and leads to mitochondrial biogenesis and to a change in mitochondrial mass. The hormone signal for the second response involves both T3-responsive nuclear genes and a direct action of T3 at mitochondrial binding sites. T3, by binding to a specific mitochondrial receptor and affecting the transcription apparatus, may thus act in a coordinated manner with the T3 nuclear pathway to regulate mitochondrial biogenesis and turnover. Transcription factors, coactivators, corepressors, signaling pathways and, perhaps, all play roles in these mechanisms. This review article focuses chiefly on TH, but also looks briefly at some analogues and derivatives (on which the data is still somewhat patchy). We summarize data obtained recently and in the past to try to obtain an updated picture of the current research position concerning the metabolic effects of TH, with particular emphasis on those exerted via mitochondria. © 2013 Elsevier Ireland Ltd
Absence of uncoupling protein-3 (UCP3) affects mice metabolic parameters and the metabolic adaptation induced by the administration of triiodothyronine to hypothyroid rats
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