Sensing of dietary lipids by enterocytes: a new role for SR-BI/CLA-1.
BACKGROUND
The 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.


RESULTS
The 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
These 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.
Béaslas
Olivier
O
Université Pierre et Marie Curie-Paris 6, UMR S 872, Les Cordeliers, Paris, France.
Cueille
Carine
C
Delers
François
F
Chateau
Danielle
D
Chambaz
Jean
J
Rousset
Monique
M
Carrière
Véronique
V
D001055:Apolipoproteins B / Q000378:metabolism; D001646:Bile / Q000378:metabolism; D018938:Caco-2 Cells; D004041:Dietary Fats / Q000378:metabolism; D020895:Enterocytes / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry*; D008823:Micelles; D008954:Models, Biological; D012307:Risk Factors; D051122:Scavenger Receptors, Class B / Q000378:metabolism*; D015398:Signal Transduction; D014280:Triglycerides / Q000378:metabolism
D001055:Apolipoproteins B; D004041:Dietary Fats; D008055:Lipids; D008823:Micelles; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D014280:Triglycerides