Intestinal apolipoprotein B secretion is inhibited by the flavonoid quercetin: potential role of microsomal triglyceride transfer protein and diacylglycerol acyltransferase.
Recent studies have yielded evidence that plant flavonoids reduce hepatic lipid and apolipoprotein B (apoB) secretion. However, the possible role of flavonoids in regulating lipid and apoB secretion by the intestine has not been studied. The purpose of our study was to examine the effects of quercetin, a common dietary flavonoid, on TAG and apoB secretion in a human intestinal cell-line, CaCo-2. Differentiated postconfluent CaCo-2 cells grown on filters and pretreated with quercetin for 8 h were shown by ELISA to inhibit basolateral apoB secretion in a dose-dependent manner. At 15 microM, the secretion of both apoB-100 and apoB-48 were inhibited similarly. This effect was shown to be specific, as quercetin did not affect the incorporation of [35S]methionine/cysteine into secreted TCA-precipitable proteins. To determine the mechanism underlying this inhibitory effect, we examined two regulatory points: TAG availability and lipid transfer to the lipoprotein particle. Quercetin inhibited TAG synthesis under both basal and lipid-rich conditions, indicating that lipid availability is a determining factor in the regulation of apoB secretion by quercetin. The reduction was due at least in part to a decrease in diacylglycerol acyltransferase activity. We next examined lipid transfer or lipidation of the lipoprotein particle by analyzing microsomal TAG transfer protein (MTP) activity. Quercetin decreased MTP activity moderately. In summary, the data demonstrated that pharmacological concentrations of quercetin are a potent inhibitor of intestinal apoB secretion and that reduced lipid availability and lipidation in the lipoprotein assembly step are the mechanism for the suppression of apoB-containing lipoprotein secretion by quercetin in CaCo-2 cells.
Casaschi
Adele
A
Division of Medical Technology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu 96822, USA.
Wang
Qi
Q
Dang
Ka'ohimanu
K
Richards
Alison
A
Theriault
Andre
A
D000217:Acyltransferases / Q000378:metabolism*; D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000378:metabolism*; D015153:Blotting, Western; D018938:Caco-2 Cells; D002352:Carrier Proteins / Q000378:metabolism*; D051048:Diacylglycerol O-Acyltransferase; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D015394:Molecular Structure; D011794:Quercetin / Q000737:chemistry / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism
D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D002352:Carrier Proteins; D014280:Triglycerides; C106092:microsomal triglyceride transfer protein; D011794:Quercetin; D000217:Acyltransferases; D051048:Diacylglycerol O-Acyltransferase