Cargando…

New avenues for regulation of lipid metabolism by thyroid hormones and analogs

Weight loss due to negative energy balance is a goal in counteracting obesity and type 2 diabetes mellitus. The thyroid is known to be an important regulator of energy metabolism through the action of thyroid hormones (THs). The classic, active TH, 3,5,3′-triiodo-L-thyronine (T3) acts predominantly...

Descripción completa

Detalles Bibliográficos
Autores principales: Senese, Rosalba, Lasala, Pasquale, Leanza, Cristina, de Lange, Pieter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4256992/
https://www.ncbi.nlm.nih.gov/pubmed/25538628
http://dx.doi.org/10.3389/fphys.2014.00475
_version_ 1782347661048807424
author Senese, Rosalba
Lasala, Pasquale
Leanza, Cristina
de Lange, Pieter
author_facet Senese, Rosalba
Lasala, Pasquale
Leanza, Cristina
de Lange, Pieter
author_sort Senese, Rosalba
collection PubMed
description Weight loss due to negative energy balance is a goal in counteracting obesity and type 2 diabetes mellitus. The thyroid is known to be an important regulator of energy metabolism through the action of thyroid hormones (THs). The classic, active TH, 3,5,3′-triiodo-L-thyronine (T3) acts predominantly by binding to nuclear receptors termed TH receptors (TRs), that recognize TH response elements (TREs) on the DNA, and so regulate transcription. T3 also acts through “non-genomic” pathways that do not necessarily involve TRs. Lipid-lowering therapies have been suggested to have potential benefits, however, the establishment of comprehensive therapeutic strategies is still awaited. One drawback of using T3 in counteracting obesity has been the occurrence of heart rhythm disturbances. These are mediated through one TR, termed TRα. The end of the previous century saw the exploration of TH mimetics that specifically bind to TR beta in order to prevent cardiac disturbances, and TH derivatives such as 3,5-diiodo-L-thyronine (T2), that possess interesting biological activities. Several TH derivatives and functional analogs have low affinity for the TRs, and are suggested to act predominantly through non-genomic pathways. All this has opened new perspectives in thyroid physiology and TH derivative usage as anti-obesity therapies. This review addresses the pros and cons of these compounds, in light of their effects on energy balance regulation and on lipid/cholesterol metabolism.
format Online
Article
Text
id pubmed-4256992
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-42569922014-12-23 New avenues for regulation of lipid metabolism by thyroid hormones and analogs Senese, Rosalba Lasala, Pasquale Leanza, Cristina de Lange, Pieter Front Physiol Physiology Weight loss due to negative energy balance is a goal in counteracting obesity and type 2 diabetes mellitus. The thyroid is known to be an important regulator of energy metabolism through the action of thyroid hormones (THs). The classic, active TH, 3,5,3′-triiodo-L-thyronine (T3) acts predominantly by binding to nuclear receptors termed TH receptors (TRs), that recognize TH response elements (TREs) on the DNA, and so regulate transcription. T3 also acts through “non-genomic” pathways that do not necessarily involve TRs. Lipid-lowering therapies have been suggested to have potential benefits, however, the establishment of comprehensive therapeutic strategies is still awaited. One drawback of using T3 in counteracting obesity has been the occurrence of heart rhythm disturbances. These are mediated through one TR, termed TRα. The end of the previous century saw the exploration of TH mimetics that specifically bind to TR beta in order to prevent cardiac disturbances, and TH derivatives such as 3,5-diiodo-L-thyronine (T2), that possess interesting biological activities. Several TH derivatives and functional analogs have low affinity for the TRs, and are suggested to act predominantly through non-genomic pathways. All this has opened new perspectives in thyroid physiology and TH derivative usage as anti-obesity therapies. This review addresses the pros and cons of these compounds, in light of their effects on energy balance regulation and on lipid/cholesterol metabolism. Frontiers Media S.A. 2014-12-05 /pmc/articles/PMC4256992/ /pubmed/25538628 http://dx.doi.org/10.3389/fphys.2014.00475 Text en Copyright © 2014 Senese, Lasala, Leanza and de Lange. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Senese, Rosalba
Lasala, Pasquale
Leanza, Cristina
de Lange, Pieter
New avenues for regulation of lipid metabolism by thyroid hormones and analogs
title New avenues for regulation of lipid metabolism by thyroid hormones and analogs
title_full New avenues for regulation of lipid metabolism by thyroid hormones and analogs
title_fullStr New avenues for regulation of lipid metabolism by thyroid hormones and analogs
title_full_unstemmed New avenues for regulation of lipid metabolism by thyroid hormones and analogs
title_short New avenues for regulation of lipid metabolism by thyroid hormones and analogs
title_sort new avenues for regulation of lipid metabolism by thyroid hormones and analogs
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4256992/
https://www.ncbi.nlm.nih.gov/pubmed/25538628
http://dx.doi.org/10.3389/fphys.2014.00475
work_keys_str_mv AT seneserosalba newavenuesforregulationoflipidmetabolismbythyroidhormonesandanalogs
AT lasalapasquale newavenuesforregulationoflipidmetabolismbythyroidhormonesandanalogs
AT leanzacristina newavenuesforregulationoflipidmetabolismbythyroidhormonesandanalogs
AT delangepieter newavenuesforregulationoflipidmetabolismbythyroidhormonesandanalogs