title: Oxygen restriction as challenge test reveals early high-fat-diet-induced changes in glucose and lipid metabolism.
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.
authors: Human and Animal Physiology, Wageningen University, De Elst 1, 6708 WD, Wageningen, The Netherlands.
authors: Loes P M
authors: LP
authors: Duivenvoorde
authors: Evert M
authors: EM
authors: van Schothorst
authors: Davina
authors: D
authors: Derous
authors: Inge
authors: I
authors: van der Stelt
authors: Jinit
authors: J
authors: Masania
authors: Naila
authors: N
authors: Rabbani
authors: Paul J
authors: PJ
authors: Thornalley
authors: Jaap
authors: J
authors: Keijer
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D005947:Glucose / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption; D062106:Protein Degradation End Products / Q000378:metabolism
chemical_list: D062106:Protein Degradation End Products; D005947:Glucose; D010100:Oxygen