Intestinal apolipoprotein B secretion is inhibited by the flavonoid quercetin: Potential role of microsomal triglyceride transfer protein and diacylglycerol acyltransferase

Abstract

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.

The liver antioxidant status of fattening lambs is improved by naringin dietary supplementation at 0.15% rates but not meat quality

“…The naringin-lowering effect on serum TAG levels might be related to an inhibitory effect of flavonoids on DGAT1 activity, one of the main enzymes involved in TAG synthesis in the liver (Casaschi et al, 2002;Jeon et al, 2004). In fact, these compounds were suggested for used in the clinical treatment of hypertriglyceridaemia (Casaschi et al, 2002).…”

“…On the other hand, the enzymatic activity of some of the proteins related to lipid metabolism (e.g. acyl-CoA : diacylglycerol acyltransferase 1 (DGAT1), acyl-CoA : cholesterol acyltransferase (ACAT), hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase) seems to be reduced by flavonoids (Casaschi et al, 2002;Jeon et al, 2002 and. However, little effort has been made to determine the effectiveness of flavonoids on the quality of ruminant products.…”

The impact of cranberry (Vaccinium macrocarpon) and cranberry products on each component of the metabolic syndrome: a review

“…The flavonoid quercetin has been shown to inhibit de novo TAG synthesis [78]. Casaschi et al [78] analyzed the activity of diacylglycerol acyltransferase (DGAT), an enzyme in the final reaction of the glycerol phosphate pathway for TAG synthesis, and found reduced DGAT activity after treatment with quercetin.…”

“…Casaschi et al [78] analyzed the activity of diacylglycerol acyltransferase (DGAT), an enzyme in the final reaction of the glycerol phosphate pathway for TAG synthesis, and found reduced DGAT activity after treatment with quercetin. The investigators also found that quercetin inhibits microsomal TAG transfer protein (MTP) activity, an enzyme that catalyzes the transfer of lipids, such as TAG and cholesterol esters, which would inhibit intestinal apolipoprotein B secretion and total cholesterol, TG and LDL levels [78].…”

“…Casaschi et al [78] analyzed the activity of diacylglycerol acyltransferase (DGAT), an enzyme in the final reaction of the glycerol phosphate pathway for TAG synthesis, and found reduced DGAT activity after treatment with quercetin. The investigators also found that quercetin inhibits microsomal TAG transfer protein (MTP) activity, an enzyme that catalyzes the transfer of lipids, such as TAG and cholesterol esters, which would inhibit intestinal apolipoprotein B secretion and total cholesterol, TG and LDL levels [78]. Ruel et al [13] Intervention study to determine the effect of the daily consumption of low-calorie cranberry juice cocktail on plasma oxidized LDL, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin concentrations in men.…”