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Oxygen restriction as challenge test reveals early high-fat-diet-induced changes in glucose and lipid metabolism
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Duivenvoorde, Loes P. M., van Schothorst, Evert M., Derous, Davina, van der Stelt, Inge, Masania, Jinit , Rabbani, Naila, Thornalley, Paul J. and Keijer, Jaap (2015) Oxygen restriction as challenge test reveals early high-fat-diet-induced changes in glucose and lipid metabolism. Pfluegers Archiv- European Journal of Physiology, 467 (6). pp. 1179-1193. doi:10.1007/s00424-014-1553-8 ISSN 0031-6768.
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Official URL: http://www.ncbi.nlm.nih.gov/pubmed/24974902
Abstract
Challenge tests stress homeostasis and may reveal deviations in health that remain masked under unchallenged conditions. Ideally, challenge tests are non-invasive and applicable in an early phase of an animal experiment. Oxygen restriction (OxR; based on ambient, mild normobaric hypoxia) is a non-invasive challenge test that measures the flexibility to adapt metabolism. Metabolic inflexibility is one of the hallmarks of the metabolic syndrome. To test whether OxR can be used to reveal early diet-induced health effects, we exposed mice to a low-fat (LF) or high-fat (HF) diet for only 5 days. The response to OxR was assessed by calorimetric measurements, followed by analysis of gene expression in liver and epididymal white adipose tissue (eWAT) and serum markers for e.g. protein glycation and oxidation. Although HF feeding increased body weight, HF and LF mice did not differ in indirect calorimetric values under normoxic conditions and in a fasting state. Exposure to OxR; however, increased oxygen consumption and lipid oxidation in HF mice versus LF mice. Furthermore, OxR induced gluconeogenesis and an antioxidant response in the liver of HF mice, whereas it induced de novo lipogenesis and an antioxidant response in eWAT of LF mice, indicating that HF and LF mice differed in their adaptation to OxR. OxR also increased serum markers of protein glycation and oxidation in HF mice, whereas these changes were absent in LF mice. Cumulatively, OxR is a promising new method to test food products on potential beneficial effects for human health.
| Item Type: | Journal Article | ||||||||||
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| Subjects: | Q Science > QP Physiology R Medicine > RC Internal medicine |
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| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Provocation tests (Medicine), Metabolism -- Testing, Lipids -- Metabolism, Adipose tissues -- Metabolism, Metabolic syndrome -- Diagnosis | ||||||||||
| Journal or Publication Title: | Pfluegers Archiv- European Journal of Physiology | ||||||||||
| Publisher: | Springer Verlag | ||||||||||
| ISSN: | 0031-6768 | ||||||||||
| Official Date: | June 2015 | ||||||||||
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| Volume: | 467 | ||||||||||
| Number: | 6 | ||||||||||
| Page Range: | pp. 1179-1193 | ||||||||||
| DOI: | 10.1007/s00424-014-1553-8 | ||||||||||
| Status: | Peer Reviewed | ||||||||||
| Publication Status: | Published | ||||||||||
| Access rights to Published version: | Restricted or Subscription Access | ||||||||||
| RIOXX Funder/Project Grant: |
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