Dietary phytosterols and phytostanols alter the expression of sterol-regulatory genes in SHRSP and WKY inbred rats.
OBJECTIVE
We elucidated the molecular mechanism(s) underlying sterol trafficking by investigating alterations in gene expression in response to increased retention of dietary phytosterols and phytostanols in stroke-prone spontaneously hypertensive (SHRSP) and normotensive Wistar Kyoto (WKY) inbred rats.


METHODS
SHRSP and WKY inbred rats were fed a control diet or a diet supplemented with phytosterols or phytostanols (2 g/kg diet).


RESULTS
Intake of phytosterols and phytostanols increased their incorporation in plasma, red blood cells, liver, aorta and kidney, but decreased cholesterol levels in liver and aorta in both rat strains. Phytosterol intake up-regulated mRNA expression of intestinal Npc1l1 and Abcg8, and hepatic Abcg5, Abca1, Cyp27a1 and Hmgcr. Phytostanol intake up-regulated Npc1l1 and Srebp2, but down-regulated Abcg5 mRNA expression in small intestine. Phytostanols also up-regulated Abca1 expression in SHRSP rats, but down-regulated Abca1 expression in WKY inbred rats. Compared to phytosterols, dietary phytostanols reduced phytosterol levels in plasma, red blood cells, and kidney, as well as altered mRNA levels of hepatic Abca1,Cyp27a1, and Hmgcr and intestinal Abcg5/8, Hmgcr and Srebp2.


CONCLUSIONS
Altered expression of multiple sterol-regulatory genes may contribute to the incorporation and cholesterol-lowering actions of phytosterols and phytostanols. Phytosterols and phytostanols may act through different mechanism(s) on cholesterol and phytosterol/phytostanol trafficking.
Nutrition Research Division, Food Directorate, Health Products and Food Branch, Health Canada, Banting Research Centre, 251 Sir Frederick Banting Driveway, Ottawa, Ontario, Canada.
Qixuan
Q
Chen
Heidi
H
Gruber
Catherine
C
Pakenham
Walisundera M N
WM
Ratnayake
Kylie A
KA
Scoggan
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D002775:Cholestadienols / Q000494:pharmacology; D002784:Cholesterol / Q000031:analogs & derivatives / Q000032:analysis / Q000097:blood / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007583:Jejunum / Q000201:enzymology* / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D009928:Organ Specificity; D010840:Phytosterols / Q000008:administration & dosage / Q000032:analysis / Q000097:blood / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012855:Sitosterols / Q000032:analysis / Q000097:blood / Q000494:pharmacology; D013261:Sterols / Q000378:metabolism*
D000924:Anticholesteremic Agents; D002775:Cholestadienols; D000960:Hypolipidemic Agents; D010840:Phytosterols; D012333:RNA, Messenger; D012855:Sitosterols; D013261:Sterols; C003532:brassicasterol; C003535:campestanol; C021273:campesterol; C025473:gamma-sitosterol; D002784:Cholesterol; C021255:stigmastanol