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

1
Human and Animal Physiology, Wageningen University, P.O. Box 338, Wageningen 6700 AH, The Netherlands
2
Laboratory of Metabolomics, Institute of Molecular and Translational Medicine, University Hospital Olomouc and Faculty of Medicine and Dentistry, Palacký University Olomouc, Hněvotinská 5, 779 00 Olomouc, Czech Republic
*
Author to whom correspondence should be addressed.
Current address: Educational Consultancy & Professional Development, Faculty of Social and Behavioural Sciences, Utrecht University, P.O. Box 80127, 3508 TC Utrecht, The Netherlands.
Genes 2019, 10(5), 359; https://doi.org/10.3390/genes10050359
Received: 15 March 2019 / Revised: 3 May 2019 / Accepted: 6 May 2019 / Published: 10 May 2019
(This article belongs to the Special Issue Gene-Diet Interactions in Obesity)
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Abstract

Obesity is associated with white adipose tissue (WAT) hypoxia and inflammation. We aimed to test whether mild environmental oxygen restriction (OxR, 13% O2), 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. View Full-Text
Keywords: hypoxia; whole genome microarray gene expression; cholecystokinin; white adipose tissue; inflammation; adipokine hypoxia; whole genome microarray gene expression; cholecystokinin; white adipose tissue; inflammation; adipokine
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Hoevenaars, F.P.M.; Keijer, J.; van der Stelt, I.; Duivenvoorde, L.P.M.; Herreman, L.; van Nes, R.; Friedecký, D.; Hegeman, M.A.; van Schothorst, E.M. White Adipose Tissue Response of Obese Mice to Ambient Oxygen Restriction at Thermoneutrality: Response Markers Identified, but no WAT Inflammation. Genes 2019, 10, 359.

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