Conjugated and non-conjugated octadecaenoic acids affect differently intestinal acyl coenzyme A: cholesterol acyltransferase activity.
We investigated the relative hypocholesterolemic activity of linoleic acid (LA), conjugated linoleic acid (CLA), alpha-linolenic acid (LN) and conjugated linolenic acid (CLN) in hamsters. Five groups of hamsters (n=10 each) were fed either the control diet or one of the four fatty acids-supplemented diets for 6 weeks. Results demonstrated that the four octadecaenoic acids decreased plasma cholesterol differently, with CLA being the most effective. Western blotting and RT-PCR analysis demonstrated that the four octadecaenoic acids had no effect on sterol regulatory element binding protein-2 (SREBP-2), liver X receptor (LXR), 3-hydroxy-3-methylglutary-CoA reductase (HMGR), LDL receptor (LDLR), and cholesterol-7alpha-hydroxylase (CYP7A1). However, the four octadecaenoic acids increased the excretion of fecal neutral sterols with CLA being most effective followed by LN, LA and CLN, suggesting they all differentially affect cholesterol absorption. Dietary CLA was associated with the least intestinal acyl coenzyme A: cholesterol acyltransferase (ACAT) activity followed by LN, LA and CLN in a decreasing trend. Since esterification of cholesterol is catalyzed by intestinal ACAT, and is a rate-limiting step in cholesterol absorption, it was concluded that the varying effects of CLA, LN, LA and CLN on blood cholesterol were mediated, at least in part, by their inhibition on intestinal ACAT activity.
Lam
Cheuk Kai
CK
Food & Nutritional Sciences Programme of Department of Biochemistry, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
Chen
Jingnan
J
Cao
Ying
Y
Yang
Lin
L
Wong
Yin Mei
YM
Yeung
Sai Ying Venus
SY
Yao
Xiaoqiang
X
Huang
Yu
Y
Chen
Zhen-Yu
ZY
D000214:Acyl Coenzyme A / Q000378:metabolism*; D000818:Animals; D001835:Body Weight; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004435:Eating; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005243:Feces; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics / Q000378:metabolism; D007422:Intestines / Q000187:drug effects / Q000201:enzymology*; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D000071518:Liver X Receptors; D008297:Male; D008647:Mesocricetus; D009929:Organ Size; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D002785:Sterol O-Acyltransferase / Q000378:metabolism*; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D013261:Sterols / Q000378:metabolism
D000214:Acyl Coenzyme A; D008076:Cholesterol, HDL; D004268:DNA-Binding Proteins; D005231:Fatty Acids, Unsaturated; D044243:Linoleic Acids, Conjugated; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011973:Receptors, LDL; D051782:Sterol Regulatory Element Binding Protein 2; D013261:Sterols; C027369:octadecadienoic acid; D006903:Hydroxymethylglutaryl CoA Reductases; D002790:Cholesterol 7-alpha-Hydroxylase; D002785:Sterol O-Acyltransferase