title: Effects of exposure to a simulated altitude of 5500 m on energy metabolic pathways in rats.
abstract: We examined the effect of exposure to 5500 m on three closely related metabolic pathways: anaerobic glycolysis, the pentose phosphate shunt (PPS), and fatty acid metabolism. Rats were exposed to simulated altitude of 5500 m for up to 3 months. The maximal rate of lactate production in tissue homogenates, tissue lactic acid dehydrogenase and blood lactate levels were measured to evaluate the capacity for anaerobic glycolysis. The uptake of 14C-1-palmitate, oxidation of 14C-1-palmitate to 14CO2, incorporation of 14C-1-palmitate into tissue lipids, plasma and tissue free fatty acids (FFA) levels and total lipid contents were measured to assess the magnitude of lipid metabolism. Activities of glucose-6-phosphate dehydrogenase (G-6-PD) and 6-phophogluconate dehydrogenase (6-PGD) in the PPS pathway were measured to assess the capacity to generate reducing power. Acute and chronic hypoxia did not affect most of the measurements of anaerobic glycolysis, but depressed lactate production in liver and kidney. Chronic hypoxia enhanced all aspects of lipid metabolism in liver and enhanced the uptake and oxidation to CO2 of palmitate in skeletal muscle. Chronic hypoxia did not alter the activity of the G-6-PD in any tissue studied, but the activity of 6-PGD was depressed in heart, kidney, thymus and adrenal gland. The lack of major changes in the capacities of anaerobic glycolytic pathways and the activities of the PPS dehydrogenases is consistent with the maintenance of normal aerobic metabolism in rats at 5500 m. We found no evidence that anaerobic metabolic processes were upregulated to sustain energy consumption during chronic hypoxia. On the other hand, enhanced fatty acid metabolism may spare carbohydrate for metabolic fuel under conditions of extreme hypoxic limitation.
authors.affiliation: Department of Physiology, Dartmouth Medical School, Lebanon, NH 03756, USA. lo.chang.ou@dartmouth.edu
authors.forename: L C
authors.initials: LC
authors.lastname: Ou
authors.forename: J C
authors.initials: JC
authors.lastname: Leiter
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology; D000531:Altitude; D015308:Anaerobic Threshold / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D004734:Energy Metabolism / Q000502:physiology; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D006019:Glycolysis / Q000502:physiology*; D007668:Kidney / Q000201:enzymology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D019344:Lactic Acid / Q000097:blood*; D008099:Liver / Q000201:enzymology; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D019308:Palmitic Acid / Q000378:metabolism*; D010427:Pentose Phosphate Pathway / Q000502:physiology*; D010734:Phosphogluconate Dehydrogenase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013687:Telencephalon / Q000201:enzymology
chemical_list: D019308:Palmitic Acid; D019344:Lactic Acid; D007770:L-Lactate Dehydrogenase; D010734:Phosphogluconate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase