Ghoshal Sarbani, Witta Jassir, Zhong Jian, de Villiers Willem, Eckhardt Erik
Department of Internal Medicine, Division of Digestive Diseases and Nutrition, University of Kentucky, Lexington, KY, USA.
J Lipid Res. 2009 Jan;50(1):90-7. doi: 10.1194/jlr.M800156-JLR200. Epub 2008 Sep 24.
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.
近期数据表明，膳食脂肪可促进肠道微生物群中脂多糖（LPS）的肠道吸收，这可能与多种炎症性疾病有关。然而，脂肪诱导LPS吸收的机制尚不清楚。肠上皮细胞可从顶端表面内化LPS并将其转运至高尔基体。高尔基体复合物还含有新形成的乳糜微粒，即通过肠系膜淋巴和血液转运膳食长链脂肪的脂蛋白。由于LPS对乳糜微粒具有亲和力，我们推测乳糜微粒的形成促进了LPS的吸收。与我们的假设一致，我们发现与丁酸（BA，一种不诱导乳糜微粒形成的短链脂肪酸）相比，用油酸（OA，一种诱导乳糜微粒形成的长链脂肪酸）孵育后，CaCo-2细胞释放出更多与细胞相关的LPS。此外，乳糜微粒形成抑制剂普朗尼克L-81可阻断OA的作用。我们还观察到，胃内灌胃三油酸甘油酯（TO）后血浆LPS升高，而灌胃三丁酸甘油酯（TB）或TO加普朗尼克L-81则不会。肠道吸收的大多数LPS存在于血液中的乳糜微粒残粒（CM-R）上。乳糜微粒的形成还促进了LPS通过肠系膜淋巴结（MLN）的转运以及MLN中肿瘤坏死因子α mRNA的产生。总之，我们的数据表明肠上皮细胞可能从细胞相关池中释放与乳糜微粒结合的LPS。与乳糜微粒相关的LPS可能导致餐后炎症反应或乳糜微粒靶组织中慢性饮食诱导的炎症。
