IN-VIVO HYPOXIC EXPOSURE IMPAIRS METABOLIC ADAPTATIONS TO A 48 HOUR FAST IN RATS

Hypoxia is well known to affect carbohydrate metabolism through its ac tion on liver function and thus on glucose homeostasis. The aim of thi s study was to examine the carbohydrate,lipid and protein metabolic re sponses to 48 h of hypoxia, as well as the hormonal adaptations using both normoxic controls and hypoxic animals in the fasted state to stan dardize for the marked hypophagia observed in response to hypoxia. Hyp oxia exposure (inspiratory oxygen fraction (FI,O-2) = 0.1) resulted in a greater weight loss (-23+/-3.6% versus -16+/-2% in controls, p < 0. 001). Hypoxia plus fasting led to a significant increase in plasma glu cose, lactate, insulin and catecholamine concentrations, while the inc rease in free fatty acid and beta-hydrosybutyrate was abolished. Chang es in plasma amino acid patterns were not affected by hypoxia, Liver g lycogen depletion was significantly less pronounced in the hypoxic gro up, while phosphoenolpyruvate carboxykinase (a key enzyme of liver glu coneogenesis) activity and transcription enhancements were abolished b y hypoxia. Overall, hypoxic exposure in rats fasted for 48 h resulted in a unique pattern that differed from responses to injury or fasting per se. Oxygen seems to play a central role in the metabolic adaptatio n to fasting, from gene expression to weight loss. Since hypoxaemia as sociated with fasting has detrimental effects on nutritional balance, the present observations mag be clinically relevant in the setting of acute exacerbation with hypoxaemia for chronic respiratory disease.