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 in 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 fatty acids with a cholesterol-free, very-low-fat semisynthetic diet, or with a diet enriched with cholesterol and saturated fat. Although the 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 transport differed in the two species. In the hamster, n-3 fatty acids had 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 saturated triglyceride. In hamsters fed n-3 fatty acids, changes in receptor-dependent LDL transport were accompanied by parallel changes in LDL receptor mRNA, indicating regulation of the receptor at the pretranslational level. In the rat, on the other hand, dietary n-3 fatty acids enhanced hepatic receptor-dependent LDL uptake by nearly twofold regardless of the background diet; however, hepatic LDL receptor protein and mRNA were unchanged. Dietary n-3 fatty acids did not enhance hepatic chylomicron remnant clearance in the rat. These studies confirm marked species differences in response to n-3 fatty acids and suggest that n-3 fatty acids accelerate hepatic receptor-dependent LDL transport in the ray by altering the distribution or recycling of LDL receptors or via effects on a different receptor pathway.