Spontaneous development of fatty liver in ferrets in a toxicology study.

Ferrets were maintained for 12 months on different diets (A, meat and biscuit; B, all meat; C, meat and fish; D, high fibre) to ascertain the cause of spontaneous development of fatty liver. High hepatic triglyceride contents resulted on diets B = C > D; whereas ferrets on diet A (control) showed no accumulation of lipid in liver. Serum triglyceride and total cholesterol were unchanged by diet. These ferrets (F0 generation) were mated with ferrets on the same diet and the offspring (F1 generation), maintained on the same diets as the parents, were killed at 12 months and the livers studied similarly. Histology showed that hepatic lipid accumulation in the F1 generation was identical with that in the same dietary groups of the F0 generation; liver glutathione (GSH) reductase and thiobarbituric acid-reacting substances (an index of lipid peroxidation) were increased in ferrets maintained on diets B, C and D, liver GSH concentration and GSH peroxidase activities were unchanged. Other ferrets fed a high-fat diet (diet A plus 20% w/w beef suet) for 18 days exhibited hepatic lipid accumulation and decreased hepatic cyanide-insensitive palmitoyl CoA oxidation (-30%), but hepatic lauric acid hydroxylation and carnitine acyl transferase activities were unchanged. These data indicate that ferrets on high-fat diets show no increased rates of liver fatty acid oxidation, as seen in rats, but instead accumulate triglyceride in the liver with some degree of lipid peroxidation.