Ketogenesis during sepsis in relation to hepatic energy metabolism.
The concentrations of acetoacetate, beta-hydroxybutyrate, and adenine nucleotides, and the mitochondrial phosphorylative activities, induced by cecal ligation and punctured in the liver of septic rats, were determined. The concentrations of glucose, free fatty acids (FFA), and free amino acids in arterial blood were also studied along with ketone body concentrations. Hepatic energy charge levels decreased from 0.84 to 0.77 at 12h after the induction of sepsis (P less than 0.01) and to 0.60 at 18h (P less than 0.001). Mitochondrial phosphorylative activity was enhanced at 6h (P less than 0.001) and decreased at 18h later. Ketone body concentrations in the liver and the arterial blood decreased concomitant with the decrease in hepatic energy charge. The mitochondrial redox state increased significantly at 12 and 18h after the induction of sepsis (P less than 0.01) concomitant with a marked decrease in the concentrations of ketone bodies (P less than 0.01). Blood glucose levels remained within normal limits except for a transient increase at 6h, but plasma FFA levels decreased (P less than 0.01). The plasma concentrations of aromatic amino acids (P less than 0.001), proline, and alanine (P less than 0.05) increased slightly at 18h. It is suggested that the ketogenic capacity of the liver is inhibited during sepsis, but that the liver maintains gluconeogenesis at relatively normal levels until a more advanced stage of sepsis.
D000227:Adenine Nucleotides / Q000378:metabolism; D000596:Amino Acids / Q000097:blood; D000818:Animals; D004734:Energy Metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005943:Gluconeogenesis; D066298:In Vitro Techniques; D007657:Ketone Bodies / Q000096:biosynthesis*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D012772:Shock, Septic / Q000378:metabolism*
D000227:Adenine Nucleotides; D000596:Amino Acids; D005230:Fatty Acids, Nonesterified; D007657:Ketone Bodies