Decrease of plasma lipid levels by polyphenols was linked to impairment of hepatic lipoprotein secretion. However, the intestine is the first epithelium that faces dietary compounds, and it contributes to lipid homeostasis by secreting triglyceride-rich lipoproteins during the postprandial state. The purpose of this study was to examine the effect of apple and wine polyphenol extracts on lipoprotein synthesis and secretion in human Caco-2/TC7 enterocytes apically supplied with complex lipid micelles. Our results clearly demonstrate that apple, but not wine, polyphenol extract dose-dependently decreases the esterification of cholesterol and the enterocyte secretion of lipoproteins. Apple polyphenols decrease apolipoprotein B (apoB) secretion by inhibiting apoB synthesis without increasing the degradation of the newly synthesized protein. Under our conditions, cholesterol uptake, apoB mRNA, and microsomal triglyceride protein activity were not modified by apple polyphenols. The main monomers present in our mixture did not interfere with the intestinal lipid metabolism. By contrast, apple procyanidins reproduced the inhibition of both cholesteryl ester synthesis and lipoprotein secretion. Overall, our results are compatible with a mechanism of action of polyphenols resulting in impaired lipid availability that could induce the inhibition of intestinal lipoprotein secretion and contribute to the hypolipidemic effect of these compounds in vivo. Fruit and vegetable consumption is consistently associated with a decrease in lipemia along with a decrease in the risk for cardiovascular diseases and stroke, diabetes, and obesity (1-3). Such effects are attributed to dietary fibers and phenolic compounds. Polyphenols, which are abundant in fruits, vegetables, and beverages such as tea and red wine, are very heterogenous, and their main classes are defined from the nature of their carbon skeletons (4). Flavonoids, the most abundant polyphenols in our diet, can be divided into several classes: flavones, flavonols, isoflavones, anthocyanins, flavanols, procyanidins, and flavanones. The protective effect of flavonoids against cardiovascular diseases has been attributed to several mechanisms, including inhibition of LDL oxidation (5) and of platelet aggregation (6) and improved endothelial function (7). More recently, it has been shown that flavonoids could interfere with the synthesis and secretion of triglyceride-rich lipoproteins (TRLs) in hepatocytes (8-10).In addition to hepatocytes, enterocytes are able to synthesize intestine-specific TRLs, namely chylomicrons, the secretion of which ensures the delivery of dietary lipids to the body. TRLs are composed of a core of neutral lipids, mostly triglyceride (TG) but also cholesteryl esters, surrounded by a monolayer of amphipathic lipids such as phospholipids and cholesterol. Apolipoprotein B (apoB) plays a major structural role in the assembly of TRLs and is required for their secretion. In humans, hepatic TRLs (i.e., VLDLs) contain an apoB-100 isoform, whereas intesti...
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