REGULATORY EFFECTS OF N-3 POLYUNSATURATED FATTY-ACIDS ON HEPATIC LDL UPTAKE IN THE HAMSTER AND RAT

These studies were undertaken to investigate the mechanisms involved i n the regulation of hepatic low density lipoprotein (LDL) transport by n-3 fatty acids in the hamster and rat. Animals were fed n-3 or n-6 f atty acids with a cholesterol-free, very-low-fat semisynthetic diet, o r with a diet enriched with cholesterol and saturated fat. Although th e enrichment of liver lipids with dietary n-3 fatty acids was similar in hamsters and rats, the effect of n-3 fatty acids on hepatic LDL tra nsport differed in the two species. In the hamster, n-3 fatty acids ha d no effect on hepatic receptor-dependent LDL uptake in animals fed a cholesterol-free, very-low-fat diet and suppressed receptor-dependent transport in animals fed a diet enriched with cholesterol and saturate d triglyceride. In hamsters fed n-3 fatty acids, changes in receptor-d ependent LDL transport were accompanied by parallel changes in LDL rec eptor mRNA, indicating regulation of the receptor at the pretranslatio nal level. In the rat, on the other hand, dietary n-3 fatty acids enha nced hepatic receptor-dependent LDL uptake by nearly twofold regardles s of the background diet; however, hepatic LDL receptor protein and mR NA were unchanged. Dietary n-3 fatty acids did not enhance hepatic chy lomicron remnant clearance in the rat. These studies confirm marked sp ecies differences in response to n-3 fatty acids and suggest that n-3 fatty acids accelerate hepatic receptor-dependent LDL transport in the rat by altering the distribution or recycling of LDL receptors or via effects on a different receptor pathway.