The control of fatty acid metabolism in liver cells from fed and starved sheep.
Isolated liver cells prepared from starved sheep converted palmitate into ketone bodies at twice the rate seen with cells from fed animals. Carnitine stimulated palmitate oxidation only in liver cells from fed sheep, and completely abolished the difference between fed and starved animals in palmitate oxidation. The rates of palmitate oxidation to CO2 and of octanoate oxidation to ketone bodies and CO2 were not affected by starvation or carnitine. Neither starvation nor carnitine altered the ratio of 3-hydroxybutyrate to acetoacetate or the rate of esterification of [1-14C]palmitate. Propionate, lactate, pyruvate and fructose inhibited ketogenesis from palmitate in cells from fed sheep. Starvation or the addition of carnitine decreased the antiketogenic effectiveness of gluconeogenic precursors. Propionate was the most potent inhibitor of ketogenesis, 0.8 mM producing 50% inhibition. Propionate, lactate, fructose and glycerol increased palmitate esterification under all conditions examined. Lactate, pyruvate and fructose stimulated oxidation of palmitate and octanoate to CO2. Starvation and the addition of gluconeogenic precursors stimulated apparent palmitate utilization by cells. Propionate, lactate and pyruvate decreased cellular long-chain acylcarnitine concentrations. Propionate decreased cell contents of CoA and acyl-CoA. It is suggested that propionate may control hepatic ketogenesis by acting at some point in the beta-oxidation sequence. The results are discussed in relation to the differences in the regulation of hepatic fatty acid metabolism between sheep and rats.
D020155:3-Hydroxybutyric Acid; D000090:Acetoacetates / Q000378:metabolism; D000818:Animals; D002331:Carnitine / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism*; D005943:Gluconeogenesis; D006885:Hydroxybutyrates / Q000378:metabolism; D066298:In Vitro Techniques; D007657:Ketone Bodies / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism; D012756:Sheep; D013217:Starvation / Q000378:metabolism
D000090:Acetoacetates; D005227:Fatty Acids; D006885:Hydroxybutyrates; D007657:Ketone Bodies; D010169:Palmitic Acids; D019308:Palmitic Acid; C016635:acetoacetic acid; D002331:Carnitine; D020155:3-Hydroxybutyric Acid