Long-chain fatty acid uptake and oxidation in the perfused liver of Walker-256 tumour-bearing rats

Abstract

Aims/Background: The effect of the Walker-256 tumour on uptake and, oxidation of long-chain fatty acids was investigated in perfused livers of rats. Methods: Isolated livers were perfused in a non-recirculating system. Fatty acid uptake, ketogenesis, oxygen uptake and 14CO2-production were measured as well as the activities of the acyl carnitine transferases I and II (CAT I and CAT II). Results: Basal oxygen uptake of livers from tumour-bearing rats was lower. Ketone bodies production derived from the long-chain fatty acids in livers from starved tumour-bearing rats was lower relative to the controls, but 14CO2 production was similar in both groups. The oxygen uptake increment and the mitochondrial NADH/NAD+ redox ratio were also decreased in tumour-bearing rats. The extent of these differences was dependent on the chain length and structure of the fatty acid, the following decreasing sequence of differences between control and tumour-bearing animals being valid: palmitate > oleate > stearate. The CAT I activity of the enzyme isolated from livers of tumour-bearing rats was half that from normal rats when palmitoyl-CoA and oleoyl-CoA were the substrates. Conclusions: Ketogenesis from exogenous fatty acids is decreased in the livers of Walker-256 tumour-bearing rats in consequence of the diminished activity of the mitochondrial CAT I. The lower rates of oxygen uptake indicate a decreased ATP synthesis, which is consistent with the in vivo lower phosphorylation potential.