Synergic hypocholesterolaemic effect ofn-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 (E 2 ) or maize oil for the last 3 weeks. Supplementation with n-3 PUFA and E 2 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, E 2 injection decreased CYP7A1 and CYP8B1 but not CYP27A1. Additionally, E 2 injection increased hepatic expression of oestrogen receptor-α and β. In conclusion, n-3 PUFA supplementation and E 2 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.

Perinatal maternal high‐fat diet promotes alterations in hepatic lipid metabolism and resistance to the hypolipidemic effect of fish oil in adolescent rat offspring

“…In rodents, n ‐3 PUFA supplementation promotes decreased serum cholesterol and hepatic cholesterol content that has been associated or not with reduced HMG CoA reductase and SREBP‐2 expression . In our study, we observed that FO reduced serum cholesterol in the adolescent standard diet offspring (Fig.…”

“…F) observed in STD offspring that received FO. N ‐3 PUFAs are also able to increase cholesterol output into the bile and its conversion to bile acids . In adolescent FO‐treated STD offspring, we observed reduced free cholesterol content (Fig.…”

Effects of diets containing linseed oil or lard and supplemented with pumpkin seeds on oxidative status, blood serum metabolites, growth performance, and meat quality of naked neck chickens

“…The decrease in cholesterol concentration may be explained by suppression of hepatic cholesterol synthesis and to enhance hepatic cholesterol breakdown. Dietary n-3 PUFAs has been reported to increase the hepatic bile acid synthesis by up-regulation and to decrease blood levels of cholesterol by down-regulation of specific enzymes in rats (Oh et al 2015). Probably, the lowering effect of higher n-3 PUFA content on serum cholesterol found in chickens fed LO diets could reflect this inhibition.…”

Associations of lifestyle and dietary habits with hyperlipidemia in Lebanon

“…Indeed, such a protective role for estrogen has been previously reported, but remains controversial. [30][31][32][33] Interestingly, in the female population included in this study, the levels of cholesterol and TG increased with age, even beyond menopause. On the other hand, it is possible that estrogen contributes to the increased levels of TG.…”