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.