RESUMO
PURPOSE OF REVIEW: The article is principally intended to describe the recent evolutions in the field of research concerned with the metabolic actions of thyroid hormones and those of some of their metabolites or derivatives. Mitochondria, as a result of their functions, represent the principal objective of scientists investigating the mechanisms underlying the effects of thyroid hormones or their metabolites/derivatives. RECENT FINDINGS: Indeed, some important recent findings concern these organelles, and in particular mitochondrial uncoupling and its modulation by effectors. Traditionally, thyroxine (T4) and tri-iodo-L-thyronine (T3) were the only thyroid hormones considered to have metabolic effects, and they alone were considered for potential as agents that might counteract some important abnormalities such as dyslipidaemias and obesity. Several observations, however, led to a reconsideration of this idea. In recent years, studies dealing with the biological activities of some natural metabolites or structural analogues of thyroid hormones have revealed abilities to ameliorate some major worldwide medical problems, such as artherosclerosis, obesity and cardiovascular diseases. Among natural metabolites, 3,5-diiodothyronine (T2) has been shown to powerfully reduce adiposity and dyslipidaemia and to reverse hepatic steatosis without unfavourable side-effects usually observed when T3 or T4 is used. Examples of synthetic analogues are GC-1 (or sobetirome) and KB2115 (or eprotirome) which show ipolipidaemic and antiaterogenic capacities. Clinical trials are in progress for these last agents. SUMMARY: In view of the above-mentioned actions, some of these compounds are now undergoing clinical trials and may have important implications for clinical practice or researches in the field of both endocrinology and metabolic-related abnormalities such as diabetes and dyslipidaemias.
Assuntos
Metabolismo dos Lipídeos , Mitocôndrias/metabolismo , Hormônios Tireóideos/metabolismo , Acetatos/farmacologia , Acetatos/uso terapêutico , Adiposidade/efeitos dos fármacos , Anilidas/farmacologia , Anilidas/uso terapêutico , Animais , Aterosclerose/tratamento farmacológico , Doenças Cardiovasculares/tratamento farmacológico , Ensaios Clínicos como Assunto , Di-Iodotironinas/farmacologia , Di-Iodotironinas/uso terapêutico , Dislipidemias/tratamento farmacológico , Metabolismo Energético/efeitos dos fármacos , Fígado Gorduroso/tratamento farmacológico , Humanos , Camundongos , Obesidade/tratamento farmacológico , Fenóis/farmacologia , Fenóis/uso terapêutico , Ratos , Hormônios Tireóideos/farmacologiaRESUMO
We investigated the mechanism by which 3,5-diiodo-l-thyronine (T2) affects skeletal muscle mitochondrial bioenergetic parameters following its acute administration to hypothyroid rats. One hour after injection, T2 increased both coupled and uncoupled respiration rates by +27% and +42%, respectively. Top-down elasticity analysis revealed that these effects were the result of increases in the substrate oxidation and mitochondrial uncoupling. Discriminating between proton-leak and redox-slip processes, we identified an increased mitochondrial proton conductance as the "pathway" underlying the effect of T2 on mitochondrial uncoupling. As a whole, these results may provide a mechanism by which T2 rapidly affects energy metabolism in hypothyroid rats.