Chylomicrons promote intestinal absorption of lipopolysaccharides

Sarbani Ghoshal^*, Jassir Witta^*, Jian Zhong^*, Willem de Villiers^*^,^, and Erik Eckhardt¹^,*^,^,

^* Department of Internal Medicine, Division of Digestive Diseases and Nutrition, University of Kentucky, Lexington, KY
Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY
Cardiovascular Research Center, University of Kentucky, Lexington, KY

Published, JLR Papers in Press, September 24, 2008.

^¹ To whom correspondence should be addressed. e-mail: eeckh2{at}uky.edu

Recent data suggest that dietary fat promotes intestinal absorptionof lipopolysaccharides (LPS) from the gut microflora, whichmight contribute to various inflammatory disorders. The mechanismof fat-induced LPS absorption is unclear, however. Intestinal-epithelialcells can internalize LPS from the apical surface and transportLPS to the Golgi. The Golgi complex also contains newly formedchylomicrons, the lipoproteins that transport dietary long-chainfat through mesenteric lymph and blood. Because LPS has affinityfor chylomicrons, we hypothesized that chylomicron formationpromotes LPS absorption. In agreement with our hypothesis, wefound that CaCo-2 cells released more cell-associated LPS afterincubation with oleic-acid (OA), a long-chain fatty acid thatinduces 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 chylomicronformation, Pluronic L-81. We also observed that intragastrictriolein (TO) gavage was followed by increased plasma LPS, whereasgavage 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 transportof LPS through mesenteric lymph nodes (MLN) and the productionof TNF ${alpha}$ mRNA in the MLN. Together, our data suggest that intestinalepithelial cells may release LPS on chylomicrons from cell-associatedpools. Chylomicron-associated LPS may contribute to postprandialinflammatory responses or chronic diet-induced inflammationin chylomicron target tissues.

Supplementary key words dietary fat • inflammation • mesenteric lymph

Abbreviations: apoB, apolipoprotein B; BA, butyric acid; CM-R, chylomicron remnants; LCT, long-chain triglycerides; LPS, lipopolysaccharides; MCT, medium chain triglycerides; MLN, mesenteric lymph nodes; OA, oleic acid; TB, tributyrin; TO, triolein

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