Oxygen restriction as a sensitive challenge test to reveal short-term diet-induced health effects

Introduction: 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 a study. The response to oxygen restriction (OxR; mild normobaric 12% O2) measures the flexibility to adapt metabolism. Metabolic inflexibility is one of the hallmarks of the metabolic syndrome. Methods: Mice were fed a low-fat (LF) or high-fat (HF) diet for only five days. Indirect calorimetry was used to assess the response to OxR. Serum markers, including protein glycation/oxidation, and gene expression in liver and adipose tissue were analysed. Results: Although HF mice had a higher body weight after five days of feeding, HF and LF mice did not differ in calorimetric values under normal conditions nor in fasting state. Exposure to OxR, however, revealed differences in substrate use and the level of oxygen consumption between both dietary groups. Furthermore, transcript levels differed significantly indicating differences in their adaptation to OxR. The adaptation in HF mice appeared to be dampened, associated with increased serum markers of protein glycation/oxidation, whereas these changes were absent in LF mice. Conclusion: An oxygen restriction challenge test is a promising new method to test food products on potential beneficial effects for health.