Abstract
BackgroundThe intestine is responsible for absorbing dietary lipids and delivering them to the organism as triglyceride-rich lipoproteins (TRL). It is important to determine how this process is regulated in enterocytes, the absorptive cells of the intestine, as prolonged postprandial hypertriglyceridemia is a known risk factor for atherosclerosis. During the postprandial period, dietary lipids, mostly triglycerides (TG) hydrolyzed by pancreatic enzymes, are combined with bile products and reach the apical membrane of enterocytes as postprandial micelles (PPM). Our aim was to determine whether these micelles induce, in enterocytes, specific early cell signaling events that could control the processes leading to TRL secretion.Methodology/Principal FindingsThe effects of supplying PPM to the apex of Caco-2/TC7 enterocytes were analyzed. Micelles devoid of TG hydrolysis products, like those present in the intestinal lumen in the interprandial period, were used as controls. The apical delivery of PPM specifically induced a number of cellular events that are not induced by interprandial micelles. These early events included the trafficking of apolipoprotein B, a structural component of TRL, from apical towards secretory domains, and the rapid, dose-dependent activation of ERK and p38MAPK. PPM supply induced the scavenger receptor SR-BI/CLA-1 to cluster at the apical brush border membrane and to move from non-raft to raft domains. Competition, inhibition or knockdown of SR-BI/CLA-1 impaired the PPM-dependent apoB trafficking and ERK activation.Conclusions/SignificanceThese results are the first evidence that enterocytes specifically sense postprandial dietary lipid-containing micelles. SR-BI/CLA-1 is involved in this process and could be a target for further study with a view to modifying intestinal TRL secretion early in the control pathway.
Highlights
The increased incidence of metabolic disorders and the ensuing atherosclerosis and cardiovascular diseases are linked to the significant changes in dietary habits that have occurred in recent decades, among which is an increase in fat intake [1]
This delocalization, which was not observed after Inter-prandial lipid micelles (IPM) supply (Figure 1), indicates that the mobilization of apical apoB depends on the supply of micellar alimentary lipids leading us to hypothesize that postprandial micelles (PPM) can induce specific signaling pathways in enterocytes
Our previous studies led us to hypothesize that dietary lipids are sensed in their physiological form of postprandial micelles (PPM) by enterocytes [14,15,16,38], a process that would trigger specific events leading enterocytes to secrete TG as triglyceriderich lipoproteins (TRL)
Summary
The increased incidence of metabolic disorders (obesity, metabolic syndromes and diabetes) and the ensuing atherosclerosis and cardiovascular diseases are linked to the significant changes in dietary habits that have occurred in recent decades, among which is an increase in fat intake [1]. It is important to characterize the mechanisms involved in the control of lipid absorption in these cells, especially those modulating the synthesis and secretion of TRL, as this could lead to the development of drugs acting on the early control steps in the intestinal transfer of dietary lipids, which could be used to reduce postprandial hypertriglyceridemia. Dietary lipids, mostly triglycerides (TG), after being hydrolyzed by pancreatic enzymes into fatty acids (FA) and monoglycerides (MG) and solubilized by bile salts and lipids in the intestinal lumen, are supplied to enterocytes as postprandial micelles (PPM). It is important to determine how this process is regulated in enterocytes, the absorptive cells of the intestine, as prolonged postprandial hypertriglyceridemia is a known risk factor for atherosclerosis. Our aim was to determine whether these micelles induce, in enterocytes, specific early cell signaling events that could control the processes leading to TRL secretion
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