Thesis (Ph.D.)--Boston University / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / The mechanisms by which diets high in saturated fat (HFD) contribute to intestinal adaptation and obesity are unknown. The hypothesis that functional changes in distal portions of small intestine are induced by HFD was tested in C57B1/6 mice. Specifically, it was examined whether the putative fatty acid translocase CD36 was phosphorylated in mouse intestinal epithelial cells and whether dephosphorylation of CD36 increased long chain fatty acid (LCFA) absorption. Co-immunoprecipitation was used to investigate specific intestinal alkaline phosphatases that might interact with CD36. It was also examined whether chronic ingestion of an HFD would lead to upregulation of the CD36 and/or one or more intestinal alkaline phosphatases that may activate CD36. CD36 was found to be phosphorylated on the surface of mouse enterocytes, indicating that there may be a phosphatase-sensitive pool of phospho-CD36 (pCD36) in mouse small intestinal tissue. CD36 was dephosphorylated by alkaline phosphatase and this treatment increased long chain but not short chain fatty acid uptake. Long chain fatty acid uptake was blocked with a specific CD36 inhibitor. CD36 from mouse small intestines physically interacted specifically with global intestinal alkaline phosphatase (gIAP) but not duodenal alkaline phosphatase (dIAP). As expected, HFD increased body weight, adiposity, and plasma triglycerides compared to control mice. CD36 and gIAP but not dIAP protein levels were significantly increased in distal but not proximal regions of intestines of HFD mice. Finally, HFD increased the absorptive capacity of the distal small intestine for LCFA in a CD36-dependent manner. It is concluded that HFD specifically upregulates gIAP protein in epithelial cells of the distal regions of the small intestine of mice, and that one of its substrates is pCD36, which has been implicated in transcellular fat transport. This diet also increases the absorptive capacity of the distal small intestine for LCFAs. Taken together, these results suggest that HFD causes intestinal adaptation that results in an increased capacity to absorb dietary fat. This effect is mediated in part by increasing the expression and activity of the fatty acid transporter CD36 and its regulatory enzyme gIAP. / 2031-01-02
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/32031 |
| Date | January 2012 |
| Creators | Lynes, Matthew D. |
| Publisher | Boston University |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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