Influence of dietary cholesterol on mitochondrial function in the rat

Rat-liver mitochondrial cholesterol ester levels were increased nine-fold and free cholesterol levels were doubled by feeding 10% lard and 2% cholesterol with Purina rabbit chow pellets to weanling male Sprague-Dawley rats for 5 weeks. This resulted in depression of State 3 (ADP-stimulated) glutamate respiration and reduced sensitivity to inhibition of phosphyorylation by tetrabutylammonium bromide and oligomycin. Brain, heart, lung, spleen, kidney and testis mitochondrial functions were not responsive to changes in dietary cholesterol nor were increases noted in free cholesterol content; mitochondrial cholesterol esters in these six tissues remained at extremely low levels regardless of treatment. Inclusion of 0.01% oleyl-p-decylbenzene sulfonate (a hypocholesterolemic agent) in the 10% lard and 2% cholesterol diet prevented elevation of rat-liver cholesterol esters and restored "normal" mitochondrial functions of respiratory control. This compound had no lowering effect on the raised level of liver mitochondrial free cholesterol nor on the reduced mitochondrial sensitivity to the phosphorylation inhibitors. We concluded that cholesterol esters were associated with depression of liver mitochondrial respiratory control and that free cholesterol was related to desensitization of mitochondria to the phosphorylation inhibitors.