Effect of treatment with alpha-p-chlorophenoxyisobutyrate and of cold exposure on the distribution of lipids in hepatic mitochondria.

Administration of alpha-p-chlorophenoxyisobutyrate (0.25% in the diet) to rats increased the liver weight, hepatic contents of ubiquinone and mitochondrial protein with no effect on the sterols. The increase was progressive with the period of drug treatment and was potentiated by simultaneous cold exposure. Withdrawal of the drug treatment as well as the cold stress resulted in a return of the liver weight and mitochondrial content to normal levels but this was not so for the ubiquinone content. Treatment with alpha-p-chlorophenoxyisobutyrate with or without cold exposure also resulted in a small but significant increase in the mitochondrial lipids which could be accounted for completely by an increase in the phospholipids with no change in the neutral lipid content. Analysis of the individual phospholipids showed that the drug treatment per se resulted in a specific increase in phosphatidylethanolamine content whereas simultaneous cold exposure or cold per se showed an increase in phosphatidylcholine. Cardiolipin content was unaffected. Mitochondria isolated from drug-treated animals maintained at an ambient or low environmental temperature showed a small but significant decrease in the respiratory control index for the oxidation of glutamate and malate whereas the coupled oxidation rates and ADP/O ratios were normal. Such a feature was also observed in the animals exposed to short periods of cold stress without the drug treatment. In all the cases the oxidation of succinate was unaffected. The role of accumulated phospholipids in the mitochondrial membranes in drug treatment and cold exposure is discussed in relation to the possible involvement in increased thermogenesis.