Role of mitochondrial enhancement in maintaining hepatic energy charge level in endotoxin shock

Abstract

The purpose of this study is to clarify the nature of apparent abnormalities in fuel substrate utilization which occur during progressive endotoxin shock and to relate these findings with its implications for circulatory behavior. After the administration of endotoxin, marked differences appeared in the time courses of hepatic energy charge and mitochondrial oxidative and phosphorylative activities between the early stage with normal blood pressure and the late stage with low blood pressure. In the early stage, the hepatic energy charge was maintained at near normal levels with a concomitant enhancement in mitochondrial oxidative and phosphorylative activities. In the late stage, this enhancement of mitochondrial oxidative and phosphorylative activities was depressed concomitant with a fall in hepatic energy charge. The mitochondrial enhancement was further associated with a fall in mitochondrial redox state, a rise in ketone body formation, and normoglycemia, indicating an acceleration of free fatty acid β-oxidation and gluconeogenesis at the early stage. In comparison, mitochondrial inhibition was accompanied by a further fall in mitochondrial redox state and hypoglycemia, indicating an inhibition of gluconeogenesis at the late stage. It is suggested that an enhancement in mitochondrial oxidative and phosphorylative activities is a protective mechanism which compensates for the fall in hepatic energy charge, and thus plays an essential role in the survival and recovery.