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Syndecan-1 Is Required to Maintain Intradermal Fat and Prevent Cold Stress

Homeostatic temperature regulation is fundamental to mammalian physiology and is controlled by acute and chronic responses of local, endocrine and nervous regulators. Here, we report that loss of the heparan sulfate proteoglycan, syndecan-1, causes a profoundly depleted intradermal fat layer, which...

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Autores principales: Kasza, Ildiko, Suh, Yewseok, Wollny, Damian, Clark, Rod J., Roopra, Avtar, Colman, Ricki J., MacDougald, Ormond A., Shedd, Timothy A., Nelson, David W., Yen, Mei-I, Yen, Chi-Liang Eric, Alexander, Caroline M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4125098/
https://www.ncbi.nlm.nih.gov/pubmed/25101993
http://dx.doi.org/10.1371/journal.pgen.1004514
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author Kasza, Ildiko
Suh, Yewseok
Wollny, Damian
Clark, Rod J.
Roopra, Avtar
Colman, Ricki J.
MacDougald, Ormond A.
Shedd, Timothy A.
Nelson, David W.
Yen, Mei-I
Yen, Chi-Liang Eric
Alexander, Caroline M.
author_facet Kasza, Ildiko
Suh, Yewseok
Wollny, Damian
Clark, Rod J.
Roopra, Avtar
Colman, Ricki J.
MacDougald, Ormond A.
Shedd, Timothy A.
Nelson, David W.
Yen, Mei-I
Yen, Chi-Liang Eric
Alexander, Caroline M.
author_sort Kasza, Ildiko
collection PubMed
description Homeostatic temperature regulation is fundamental to mammalian physiology and is controlled by acute and chronic responses of local, endocrine and nervous regulators. Here, we report that loss of the heparan sulfate proteoglycan, syndecan-1, causes a profoundly depleted intradermal fat layer, which provides crucial thermogenic insulation for mammals. Mice without syndecan-1 enter torpor upon fasting and show multiple indicators of cold stress, including activation of the stress checkpoint p38α in brown adipose tissue, liver and lung. The metabolic phenotype in mutant mice, including reduced liver glycogen, is rescued by housing at thermoneutrality, suggesting that reduced insulation in cool temperatures underlies the observed phenotypes. We find that syndecan-1, which functions as a facultative lipoprotein uptake receptor, is required for adipocyte differentiation in vitro. Intradermal fat shows highly dynamic differentiation, continuously expanding and involuting in response to hair cycle and ambient temperature. This physiology probably confers a unique role for Sdc1 in this adipocyte sub-type. The PPARγ agonist rosiglitazone rescues Sdc1−/− intradermal adipose tissue, placing PPARγ downstream of Sdc1 in triggering adipocyte differentiation. Our study indicates that disruption of intradermal adipose tissue development results in cold stress and complex metabolic pathology.
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spelling pubmed-41250982014-08-12 Syndecan-1 Is Required to Maintain Intradermal Fat and Prevent Cold Stress Kasza, Ildiko Suh, Yewseok Wollny, Damian Clark, Rod J. Roopra, Avtar Colman, Ricki J. MacDougald, Ormond A. Shedd, Timothy A. Nelson, David W. Yen, Mei-I Yen, Chi-Liang Eric Alexander, Caroline M. PLoS Genet Research Article Homeostatic temperature regulation is fundamental to mammalian physiology and is controlled by acute and chronic responses of local, endocrine and nervous regulators. Here, we report that loss of the heparan sulfate proteoglycan, syndecan-1, causes a profoundly depleted intradermal fat layer, which provides crucial thermogenic insulation for mammals. Mice without syndecan-1 enter torpor upon fasting and show multiple indicators of cold stress, including activation of the stress checkpoint p38α in brown adipose tissue, liver and lung. The metabolic phenotype in mutant mice, including reduced liver glycogen, is rescued by housing at thermoneutrality, suggesting that reduced insulation in cool temperatures underlies the observed phenotypes. We find that syndecan-1, which functions as a facultative lipoprotein uptake receptor, is required for adipocyte differentiation in vitro. Intradermal fat shows highly dynamic differentiation, continuously expanding and involuting in response to hair cycle and ambient temperature. This physiology probably confers a unique role for Sdc1 in this adipocyte sub-type. The PPARγ agonist rosiglitazone rescues Sdc1−/− intradermal adipose tissue, placing PPARγ downstream of Sdc1 in triggering adipocyte differentiation. Our study indicates that disruption of intradermal adipose tissue development results in cold stress and complex metabolic pathology. Public Library of Science 2014-08-07 /pmc/articles/PMC4125098/ /pubmed/25101993 http://dx.doi.org/10.1371/journal.pgen.1004514 Text en © 2014 Kasza et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Kasza, Ildiko
Suh, Yewseok
Wollny, Damian
Clark, Rod J.
Roopra, Avtar
Colman, Ricki J.
MacDougald, Ormond A.
Shedd, Timothy A.
Nelson, David W.
Yen, Mei-I
Yen, Chi-Liang Eric
Alexander, Caroline M.
Syndecan-1 Is Required to Maintain Intradermal Fat and Prevent Cold Stress
title Syndecan-1 Is Required to Maintain Intradermal Fat and Prevent Cold Stress
title_full Syndecan-1 Is Required to Maintain Intradermal Fat and Prevent Cold Stress
title_fullStr Syndecan-1 Is Required to Maintain Intradermal Fat and Prevent Cold Stress
title_full_unstemmed Syndecan-1 Is Required to Maintain Intradermal Fat and Prevent Cold Stress
title_short Syndecan-1 Is Required to Maintain Intradermal Fat and Prevent Cold Stress
title_sort syndecan-1 is required to maintain intradermal fat and prevent cold stress
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4125098/
https://www.ncbi.nlm.nih.gov/pubmed/25101993
http://dx.doi.org/10.1371/journal.pgen.1004514
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