Abstract
Recent data suggest that dietary fat promotes intestinal absorption of lipopolysaccharides (LPS) from the gut microflora, which might contribute to various inflammatory disorders. The mechanism of fat-induced LPS absorption is unclear, however. Intestinal-epithelial cells can internalize LPS from the apical surface and transport LPS to the Golgi. The Golgi complex also contains newly formed chylomicrons, the lipoproteins that transport dietary long-chain fat through mesenteric lymph and blood. Because LPS has affinity for chylomicrons, we hypothesized that chylomicron formation promotes LPS absorption. In agreement with our hypothesis, we found that CaCo-2 cells released more cell-associated LPS after incubation with oleic-acid (OA), a long-chain fatty acid that induces chylomicron formation, than with butyric acid (BA), a short-chain fatty acid that does not induce chylomicron formation. Moreover, the effect of OA was blocked by the inhibitor of chylomicron formation, Pluronic L-81. We also observed that intragastric triolein (TO) gavage was followed by increased plasma LPS, whereas gavage with tributyrin (TB), or TO plus Pluronic L-81, was not. Most intestinally absorbed LPS was present on chylomicron remnants (CM-R) in the blood. Chylomicron formation also promoted transport of LPS through mesenteric lymph nodes (MLN) and the production of TNFalpha mRNA in the MLN. Together, our data suggest that intestinal epithelial cells may release LPS on chylomicrons from cell-associated pools. Chylomicron-associated LPS may contribute to postprandial inflammatory responses or chronic diet-induced inflammation in chylomicron target tissues.
Highlights
Recent data suggest that dietary fat promotes intestinal absorption of lipopolysaccharides (LPS) from the gut microflora, which might contribute to various inflammatory disorders
This could occur through so called intestinal-epithelial microfold cells (M-cells), which are permeable to bacteria and macromolecules and facilitate sampling of gut antigens by the underlying lymphoid tissue [21]
Uptake of bacteria and LPS may not be limited to Mcells, and has been demonstrated to occur in absorptive enterocytes [22] where it may relate to the known induction of LPS tolerance in these cells [23, 24]
Summary
Recent data suggest that dietary fat promotes intestinal absorption of lipopolysaccharides (LPS) from the gut microflora, which might contribute to various inflammatory disorders. Excess dietary fat increases systemic exposure to potentially proinflammatory free fatty acids and their derivatives, but its intestinal absorption was recently found to facilitate the absorption of highly proinflammatory bacterial lipopolysaccharides (LPS) from the gut [11, 12]. This is highly interesting, because the absorbed LPS might affect whole body inflammation and interfere with metabolism and the function of the immune system. Dietary long-chain fat is transported from the absorptive enterocyte to extra-intestinal tissue after its incorporation as triglycerides into chylomicrons and its release into mesenteric lymph. We hypothesized that chylomicron secretion would result in concomitant basolateral secretion of LPS from cell-associated pools
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