title: Synergic hypocholesterolaemic effect of n-3 PUFA and oestrogen by modulation of hepatic cholesterol metabolism in female rats.
abstract: n-3 PUFA such as EPA and DHA as well as oestrogen have been reported to decrease blood levels of cholesterol, but their underlying mechanism is unclear. The purpose of this study was to determine the effects of the combination of n-3 PUFA supplementation and oestrogen injection on hepatic cholesterol metabolism. Rats were fed a modified AIN-93G diet with 0, 1 or 2 % n-3 PUFA (EPA+DHA) relative to the total energy intake for 12 weeks. Rats were surgically ovariectomised at week 8, and, after 1-week recovery, rats were injected with 17β-oestradiol-3-benzoate (E2) or maize oil for the last 3 weeks. Supplementation with n-3 PUFA and E2 injection significantly increased the ratio of the hepatic expression of phosphorylated AMP activated protein kinase (p-AMPK):AMP activated protein kinase (AMPK) and decreased sterol regulatory element-binding protein-2, 3-hydroxy-3-methylglutaryl coenzyme A reductase and proprotein convertase subtilisin/kexin type 9. Supplementation with n-3 PUFA increased hepatic expression of cholesterol 7α-hydroxylase (CYP7A1), sterol 12α-hydroxylase (CYP8B1) and sterol 27-hydroxylase (CYP27A1); however, E2 injection decreased CYP7A1 and CYP8B1 but not CYP27A1. Additionally, E2 injection increased hepatic expression of oestrogen receptor-α and β. In conclusion, n-3 PUFA supplementation and E2 injection had synergic hypocholesterolaemic effects by down-regulating hepatic cholesterol synthesis (n-3 PUFA and oestrogen) and up-regulating bile acid synthesis (n-3 PUFA) in ovariectomised rats.
authors.affiliation: Department of Food and Nutrition,Hanyang University,Seoul 133-791,South Korea.
authors.forename: Yuna
authors.initials: Y
authors.lastname: Oh
authors.affiliation: Department of Food and Nutrition,Hanyang University,Seoul 133-791,South Korea.
authors.forename: Youri
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Food and Nutrition,Hanyang University,Seoul 133-791,South Korea.
authors.forename: Yongsoon
authors.initials: Y
authors.lastname: Park
mesh_terms: D000375:Aging; D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D053493:Cholestanetriol 26-Monooxygenase / Q000737:chemistry / Q000378:metabolism; D002790:Cholesterol 7-alpha-Hydroxylase / Q000737:chemistry / Q000378:metabolism; D003131:Combined Modality Therapy; D018752:Diet, Fat-Restricted; D019587:Dietary Supplements; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D004967:Estrogens / Q000008:administration & dosage / Q000627:therapeutic use*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006903:Hydroxymethylglutaryl CoA Reductases / Q000737:chemistry / Q000378:metabolism; D006937:Hypercholesterolemia / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010052:Ovariectomy; D000071449:Proprotein Convertase 9; D011897:Random Allocation; D017208:Rats, Wistar; D012697:Serine Endopeptidases / Q000737:chemistry / Q000378:metabolism; D013253:Steroid 12-alpha-Hydroxylase / Q000737:chemistry / Q000378:metabolism; D051782:Sterol Regulatory Element Binding Protein 2 / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000924:Anticholesteremic Agents; D004967:Estrogens; D015525:Fatty Acids, Omega-3; D051782:Sterol Regulatory Element Binding Protein 2; C074283:estradiol 3-benzoate; D004958:Estradiol; D006903:Hydroxymethylglutaryl CoA Reductases; C532838:CYP7A1 protein, rat; D002790:Cholesterol 7-alpha-Hydroxylase; D053493:Cholestanetriol 26-Monooxygenase; C000604971:Cyp27a1 protein, rat; D013253:Steroid 12-alpha-Hydroxylase; C510804:PCSK9 protein, rat; D000071449:Proprotein Convertase 9; D012697:Serine Endopeptidases
keywords:     n-3 PUFA; AMPK AMP activated protein kinase; CYP27A1 sterol 27-hydroxylase; CYP7A1 cholesterol 7α-hydroxylase; CYP8B1 sterol 12α-hydroxylase; Cholesterol metabolism; E2 17β-oestradiol-3-benzoate; ER-α oestrogen receptor-α; ER-β oestrogen receptor-β; HMG-CoA reductase 3-hydroxy-3-methylglutaryl coenzyme A reductase; Oestrogen; Ovariectomised rats; Proprotein convertase subtilisin/kexin type 9; SREBP-2 sterol regulatory element-binding protein-2; TC total cholesterol; p-AMPK phosphorylated AMP activated protein kinase