Hepatic mitochondrial respiration and transport of reducing equivalents in rats fed an energy dense diet.

OBJECTIVE: To measure hepatic mitochondrial respiration as well as the ability of hepatic mitochondria to transport reducing equivalents by shuttle systems in rats fed an energy dense diet. DESIGN: Rats were fed a control (CD) or energy dense (ED) diet for 15 days. MEASUREMENTS: State 3 and State 4 oxygen consumption were measured in isolated mitochondria using glutamate+malate or pyruvate+malate as substrate. We also measured malate-aspartate shuttle activity and mitochondrial alpha-glycerophosphate dehydrogenase activity. RESULTS: ED rats, in comparison with CD rats, showed a significantly greater energy intake without a corresponding greater body weight gain and carcass lipid content. Compared to CD rats, ED rats also showed a significant increase in resting metabolic rate, which was abolished by propranolol. Hepatic mitochondrial state 3 respiration using glutamate+malate or pyruvate+malate as substrate as well as malate-aspartate shuttle activity significantly decreased, while mitochondrial alpha-glycerophosphate dehydrogenase significantly increased in ED rats compared to CD rats. CONCLUSIONS: Mitochondrial NADH oxidation is reduced and a greater fraction of cytoplasmic NADH can be transported to the mitochondria through the alpha-glycerophosphate shuttle and oxidized through the respiratory chain from complex II onwards. This mechanism could lead to a decrease in hepatic metabolic efficiency which is in line with the increased energy expenditure occurring in rats fed an energy dense diet.