title: Regulatory effects of n-3 polyunsaturated fatty acids on hepatic LDL uptake in the hamster and rat.
abstract: 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 rat by altering the distribution or recycling of LDL receptors or via effects on a different receptor pathway.
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas 75235-8887, USA.
authors.forename: D K
authors.initials: DK
authors.lastname: Spady
authors.forename: J D
authors.initials: JD
authors.lastname: Horton
authors.forename: J A
authors.initials: JA
authors.lastname: Cuthbert
mesh_terms: D000818:Animals; D001483:Base Sequence; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008647:Mesocricetus / Q000378:metabolism*; D008969:Molecular Sequence Data; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000378:metabolism*; D013045:Species Specificity
chemical_list: D015525:Fatty Acids, Omega-3; D008077:Lipoproteins, LDL