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White Adipose Tissue Response of Obese Mice to Ambient Oxygen Restriction at Thermoneutrality: Response Markers Identified, but no WAT Inflammation

Obesity is associated with white adipose tissue (WAT) hypoxia and inflammation. We aimed to test whether mild environmental oxygen restriction (OxR, 13% O(2)), imposing tissue hypoxia, triggers WAT inflammation in obese mice. Thirteen weeks diet-induced obese male adult C57BL/6JOlaHsd mice housed at...

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Autores principales: Hoevenaars, Femke P. M., Keijer, Jaap, van der Stelt, Inge, Duivenvoorde, Loes P. M., Herreman, Laure, van Nes, Robin, Friedecký, David, Hegeman, Maria A., van Schothorst, Evert M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562665/
https://www.ncbi.nlm.nih.gov/pubmed/31083422
http://dx.doi.org/10.3390/genes10050359
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author Hoevenaars, Femke P. M.
Keijer, Jaap
van der Stelt, Inge
Duivenvoorde, Loes P. M.
Herreman, Laure
van Nes, Robin
Friedecký, David
Hegeman, Maria A.
van Schothorst, Evert M.
author_facet Hoevenaars, Femke P. M.
Keijer, Jaap
van der Stelt, Inge
Duivenvoorde, Loes P. M.
Herreman, Laure
van Nes, Robin
Friedecký, David
Hegeman, Maria A.
van Schothorst, Evert M.
author_sort Hoevenaars, Femke P. M.
collection PubMed
description Obesity is associated with white adipose tissue (WAT) hypoxia and inflammation. We aimed to test whether mild environmental oxygen restriction (OxR, 13% O(2)), imposing tissue hypoxia, triggers WAT inflammation in obese mice. Thirteen weeks diet-induced obese male adult C57BL/6JOlaHsd mice housed at thermoneutrality were exposed for five days to OxR versus normoxia. WAT and blood were isolated and used for analysis of metabolites and adipokines, WAT histology and macrophage staining, and WAT transcriptomics. OxR increased circulating levels of haemoglobin and haematocrit as well as hypoxia responsive transcripts in WAT and decreased blood glucose, indicating systemic and tissue hypoxia. WAT aconitase activity was inhibited. Macrophage infiltration as marker for WAT inflammation tended to be decreased, which was supported by down regulation of inflammatory genes S100a8, Ccl8, Clec9a, Saa3, Mgst2, and Saa1. Other down regulated processes include cytoskeleton remodelling and metabolism, while response to hypoxia appeared most prominently up regulated. The adipokines coiled-coil domain containing 3 (CCDC3) and adiponectin, as well as the putative WAT hormone cholecystokinin (CCK), were reduced by OxR on transcript (Cck, Ccdc3) and/or serum protein level (adiponectin, CCDC3). Conclusively, our data demonstrate that also in obese mice OxR does not trigger WAT inflammation. However, OxR does evoke a metabolic response in WAT, with CCDC3 and adiponectin as potential markers for systemic or WAT hypoxia.
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spelling pubmed-65626652019-06-17 White Adipose Tissue Response of Obese Mice to Ambient Oxygen Restriction at Thermoneutrality: Response Markers Identified, but no WAT Inflammation Hoevenaars, Femke P. M. Keijer, Jaap van der Stelt, Inge Duivenvoorde, Loes P. M. Herreman, Laure van Nes, Robin Friedecký, David Hegeman, Maria A. van Schothorst, Evert M. Genes (Basel) Article Obesity is associated with white adipose tissue (WAT) hypoxia and inflammation. We aimed to test whether mild environmental oxygen restriction (OxR, 13% O(2)), imposing tissue hypoxia, triggers WAT inflammation in obese mice. Thirteen weeks diet-induced obese male adult C57BL/6JOlaHsd mice housed at thermoneutrality were exposed for five days to OxR versus normoxia. WAT and blood were isolated and used for analysis of metabolites and adipokines, WAT histology and macrophage staining, and WAT transcriptomics. OxR increased circulating levels of haemoglobin and haematocrit as well as hypoxia responsive transcripts in WAT and decreased blood glucose, indicating systemic and tissue hypoxia. WAT aconitase activity was inhibited. Macrophage infiltration as marker for WAT inflammation tended to be decreased, which was supported by down regulation of inflammatory genes S100a8, Ccl8, Clec9a, Saa3, Mgst2, and Saa1. Other down regulated processes include cytoskeleton remodelling and metabolism, while response to hypoxia appeared most prominently up regulated. The adipokines coiled-coil domain containing 3 (CCDC3) and adiponectin, as well as the putative WAT hormone cholecystokinin (CCK), were reduced by OxR on transcript (Cck, Ccdc3) and/or serum protein level (adiponectin, CCDC3). Conclusively, our data demonstrate that also in obese mice OxR does not trigger WAT inflammation. However, OxR does evoke a metabolic response in WAT, with CCDC3 and adiponectin as potential markers for systemic or WAT hypoxia. MDPI 2019-05-10 /pmc/articles/PMC6562665/ /pubmed/31083422 http://dx.doi.org/10.3390/genes10050359 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hoevenaars, Femke P. M.
Keijer, Jaap
van der Stelt, Inge
Duivenvoorde, Loes P. M.
Herreman, Laure
van Nes, Robin
Friedecký, David
Hegeman, Maria A.
van Schothorst, Evert M.
White Adipose Tissue Response of Obese Mice to Ambient Oxygen Restriction at Thermoneutrality: Response Markers Identified, but no WAT Inflammation
title White Adipose Tissue Response of Obese Mice to Ambient Oxygen Restriction at Thermoneutrality: Response Markers Identified, but no WAT Inflammation
title_full White Adipose Tissue Response of Obese Mice to Ambient Oxygen Restriction at Thermoneutrality: Response Markers Identified, but no WAT Inflammation
title_fullStr White Adipose Tissue Response of Obese Mice to Ambient Oxygen Restriction at Thermoneutrality: Response Markers Identified, but no WAT Inflammation
title_full_unstemmed White Adipose Tissue Response of Obese Mice to Ambient Oxygen Restriction at Thermoneutrality: Response Markers Identified, but no WAT Inflammation
title_short White Adipose Tissue Response of Obese Mice to Ambient Oxygen Restriction at Thermoneutrality: Response Markers Identified, but no WAT Inflammation
title_sort white adipose tissue response of obese mice to ambient oxygen restriction at thermoneutrality: response markers identified, but no wat inflammation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562665/
https://www.ncbi.nlm.nih.gov/pubmed/31083422
http://dx.doi.org/10.3390/genes10050359
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