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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...

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Detalles Bibliográficos
Autores principales: Bast-Habersbrunner, Andrea, Fromme, Tobias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
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.
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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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