Cerebral phosphoinositide, triacylglycerol and energy metabolism during severe hypoxia and recovery.
The cerebral concentrations of phosphatidylinositol (PI), phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol 4,5-bisphosphate (PIP2), phosphatidic acid (PA), triacylglycerol (TAG) and free fatty acids (FFA), as well as cerebral metabolites, were measured in rats subjected to 10 min of hypoxia and subsequent recovery of 7 or 30 min duration. The experiments were carried out with control of physiological variables. Hypoxia (paO2 values of about 15 mm Hg) caused a decrease in PI, whereas PIP and PIP2 did not change significantly. A two-fold increase of total FFA was noted, mainly comprising stearic and arachidonic acids. TAG-arachidonate tended to increase, but the other species in TAG decreased. Adenosine triphosphate (ATP) and energy charge (EC) decreased slightly and there was a marked lactate accumulation. PA did not change throughout the experiment. With recovery of 7 min duration, PI decreased further and total FFA continued to increase. TAG-arachidonate increased significantly. ATP remained depressed but EC recovered to the control range. Both tissue and plasma glucose increased. Tissue lactate remained elevated and systemic acidosis occurred. After a recovery period of 30 min, all lipids normalized and the energy state returned toward control. The data suggest that the phosphoinositide alterations during hypoxia are metabolically linked to changes in FFA and the lipid changes are accompanied by alterations in cerebral energy and carbohydrate metabolism. The selective increase in TAG-arachidonate may represent an incorporation of arachidonic acid into TAG, which may serve to reduce the free arachidonic acid level in the brain.
Ikeda
M
M
Department of Neurology, University of Miami School of Medicine, FL 33101.
Busto
R
R
Yoshida
S
S
Santiso
M
M
Martinez
E
E
Ginsberg
M D
MD
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D050356:Lipid Metabolism; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D014280:Triglycerides / Q000378:metabolism*
D005227:Fatty Acids; D010716:Phosphatidylinositols; D011773:Pyruvates; D014280:Triglycerides; D010725:Phosphocreatine; D019289:Pyruvic Acid; D006003:Glycogen