Depression of respiratory activities by fatty acids in liver mitochondria from diabetic rats and hormonal regulation of mitochondrial fatty acids.

Abstract

Liver mitochondria were prepared from normal, adrenalectomized, thyroidectomized or hypophysectomized rats and the respiratory activities were measured polarogra-phically. The oxidative phosphorylation (P/O ratio) and the respiratory control were not greatly disturbed in the hormone-deficient rats, although the respiratory rates, both in states 3 and 4, were markedly decreased in the thyroidectomized and hypophysectomized rats. By in vivo administration of alloxan to normal rats, the mito-chondrial content of non-esterified fatty acids was extremely increased and uncoupling of respiration was elicited, whereas the administration of alloxan to the hormone-deficient rats produced neither hyperlipemia nor fatty liver even in the presence of hyperglycemia, and the free fatty acid content of the liver mitochondria was within the normal range. The respiratory patterns of mitochondria from the hormone-deficient rats were normal even after the administration of alloxan. The efficiency of oxidative phosphorylation and the ratio of respiratory control of mitochondria from these animals were also not altered by the administration of alloxan in vivo. These results seem to support the view that the disturbance of respiratory activity of liver mitochondria from diabetic rats may be caused by the elevation of the content of non-esterified fatty acids, and that the fatty acid content in turn may be regulated by the hormones secreted from the adrenal, thyroid and pituitary glands.