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Purine Nucleotides in the Regulation of Brown Adipose Tissue Activity
Non-shivering thermogenesis in mammalian brown adipose tissue is a powerful mechanism to defend normothermia in cold climates. To minimize the loss of chemical energy, the central functional component, mitochondrial uncoupling protein 1, UCP1, must be tightly regulated. The canonical pathway of UCP1...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076073/ https://www.ncbi.nlm.nih.gov/pubmed/32210919 http://dx.doi.org/10.3389/fendo.2020.00118 |
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author | Bast-Habersbrunner, Andrea Fromme, Tobias |
author_facet | Bast-Habersbrunner, Andrea Fromme, Tobias |
author_sort | Bast-Habersbrunner, Andrea |
collection | PubMed |
description | Non-shivering thermogenesis in mammalian brown adipose tissue is a powerful mechanism to defend normothermia in cold climates. To minimize the loss of chemical energy, the central functional component, mitochondrial uncoupling protein 1, UCP1, must be tightly regulated. The canonical pathway of UCP1 activation includes lipolytic release of free fatty acids in response to an adrenergic signal. Activating fatty acids overcome constitutive inhibition of UCP1 by the di- and triphosphate forms of purine nucleotides, i.e., ATP, ADP, GTP, and GDP. Cellular concentrations of inhibitory, free nucleotides are subject to significant, adrenergically induced alterations. The regulatory components involved may constitute novel drug targets to manipulate brown fat thermogenesis and thereby organismic energy balance. We here review evidence for and against a dominant role of nucleotides in thermogenic control, describe conceptual routes to endogenously and pharmacologically alter free nucleotide pool size, speculate on a signaling role of degradation products released from active brown fat, and highlight gaps in our understanding of signaling and metabolic pathways involved. |
format | Online Article Text |
id | pubmed-7076073 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-70760732020-03-24 Purine Nucleotides in the Regulation of Brown Adipose Tissue Activity Bast-Habersbrunner, Andrea Fromme, Tobias Front Endocrinol (Lausanne) Endocrinology Non-shivering thermogenesis in mammalian brown adipose tissue is a powerful mechanism to defend normothermia in cold climates. To minimize the loss of chemical energy, the central functional component, mitochondrial uncoupling protein 1, UCP1, must be tightly regulated. The canonical pathway of UCP1 activation includes lipolytic release of free fatty acids in response to an adrenergic signal. Activating fatty acids overcome constitutive inhibition of UCP1 by the di- and triphosphate forms of purine nucleotides, i.e., ATP, ADP, GTP, and GDP. Cellular concentrations of inhibitory, free nucleotides are subject to significant, adrenergically induced alterations. The regulatory components involved may constitute novel drug targets to manipulate brown fat thermogenesis and thereby organismic energy balance. We here review evidence for and against a dominant role of nucleotides in thermogenic control, describe conceptual routes to endogenously and pharmacologically alter free nucleotide pool size, speculate on a signaling role of degradation products released from active brown fat, and highlight gaps in our understanding of signaling and metabolic pathways involved. Frontiers Media S.A. 2020-03-10 /pmc/articles/PMC7076073/ /pubmed/32210919 http://dx.doi.org/10.3389/fendo.2020.00118 Text en Copyright © 2020 Bast-Habersbrunner and Fromme. 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) and the copyright owner(s) 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 | Endocrinology Bast-Habersbrunner, Andrea Fromme, Tobias Purine Nucleotides in the Regulation of Brown Adipose Tissue Activity |
title | Purine Nucleotides in the Regulation of Brown Adipose Tissue Activity |
title_full | Purine Nucleotides in the Regulation of Brown Adipose Tissue Activity |
title_fullStr | Purine Nucleotides in the Regulation of Brown Adipose Tissue Activity |
title_full_unstemmed | Purine Nucleotides in the Regulation of Brown Adipose Tissue Activity |
title_short | Purine Nucleotides in the Regulation of Brown Adipose Tissue Activity |
title_sort | purine nucleotides in the regulation of brown adipose tissue activity |
topic | Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076073/ https://www.ncbi.nlm.nih.gov/pubmed/32210919 http://dx.doi.org/10.3389/fendo.2020.00118 |
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