Adaptation to Chronic Hypoxia During Diet-Induced Ketosis

It is recognized that brain oxygen deprivation results in increased glycolysis and lactate accumulation. Moreover, glucose metabolism is altered during starvation or diet, resulting in increased plasma ketones (acetoacetate + beta-hydroxybutyrate; BHB). We investigated glucose and lactate adaptation to hypoxia in concurrence with diet-induced ketosis. Male Wistar rats were fed standard (STD), ketogenic (high fat; KG), or carbohydrate-rich (low fat; CHO) diets for 3 wks and then exposed to hypobaric (0.5 ATM) or normobaric atmosphere for 3 wks while on their diets. Lactate, ketones, and glucose concentrations were measured in plasma (mM) and brain tissue (mmol/g). Plasma and tissue ketone levels were elevated up to 12-fold in the KG fed groups compared with other groups (STD and CHO), with the hypoxic KG group reaching the highest levels (2.6 +/- 1.3 mM and 0.3 +/- 0.1 mmol/g; mean +/- SD). Tissue lactate levels in the hypoxic ketotic rats (4.7 +/- 1.3 mM) were comparable with normoxic STD (5.0 +/- 0.7 mM) and significantly lower (ANOVA P < .05) than the hypoxic STD rats (6.1 +/- 1.0 mM). These data indicate that adaptation to hypoxia did not interfere with ketosis, and that ketosis during hypoxia may lower lactate levels in brain, suggesting decreased glycolysis or increased glucose disposal.