Intestinal caveolin-1 is important for dietary fatty acid absorption |
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Authors: | Shahzad Siddiqi Atur Sheth Feenalie Patel Matthew Barnes Charles M. Mansbach II |
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Affiliation: | 1. Division of Gastroenterology, Department of Medicine, The University of Tennessee Health Science Center, 38163 USA;2. Veterans Affairs Medical Center, Memphis, TN 38104, USA |
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Abstract: | How dietary fatty acids are absorbed into the enterocyte and transported to the ER is not established. We tested the possibility that caveolin-1 containing lipid rafts and endocytic vesicles were involved. Apical brush border membranes took up 15% of albumin bound 3H-oleate whereas brush border membranes from caveolin-1 KO mice took up only 1%. In brush border membranes, the 3H-oleate was in the detergent resistant fraction of an OptiPrep gradient. On OptiPrep gradients of intestinal cytosol, we also found the 3H-oleate in the detergent resistant fraction, separate from OptiPrep gradients spiked with 3H-oleate or 3H-triacylglycerol. Caveolin-1 immuno-depletion of cytosol removed 91% of absorbed 3H-oleate whereas immuno-depletion using IgG, or anti-caveolin-2 or -3 or anti-clathrin antibodies removed 20%. Electron microscopy showed the presence of caveolin-1 containing vesicles in WT mouse cytosol that were 4 fold increased by feeding intestinal sacs 1 mM oleate. No vesicles were seen in caveolin-1 KO mouse cytosol. Caveolin-1 KO mice gained less weight on a 23% fat diet and had increased fat in their stool compared to WT mice. We conclude that dietary fatty acids are absorbed by caveolae in enterocyte brush border membranes, are endocytosed, and transported in cytosol in caveolin-1 containing endocytic vesicles. |
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Keywords: | TAG, triacylglycerol FA, fatty acid MAG, sn-2-monoacylglycerol FAT, fatty acid translocase CD36, cluster of differentiation 36 FABPpm, fatty acid binding protein plasma membrane FABP1, liver fatty acid binding protein FABP2, intestinal fatty acid binding protein WT, wild type KO, knockout GPI, glycosylphosphatidylinositol IAP, intestinal alkaline phosphatase ECL, enhanced chemiluminescence FATP4, fatty acid transport protein 4 PBS, phosphate buffered saline MBC, methyl ß cyclodextrin ACSL, acyl-Co-A synthetase long chain DRM, detergent resistant membranes DSF, detergent soluble fraction EM, electron microscopy BB, brush border CEV, caveolin-1 containing endocytic vesicles |
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