Texas A&M University LibrariesTexas A&M University LibrariesTexas A&M University Libraries
    • Help
    • Login
    OAKTrust
    View Item 
    •   OAKTrust Home
    • Colleges and Schools
    • Office of Graduate and Professional Studies
    • Electronic Theses, Dissertations, and Records of Study (2002– )
    • View Item
    •   OAKTrust Home
    • Colleges and Schools
    • Office of Graduate and Professional Studies
    • Electronic Theses, Dissertations, and Records of Study (2002– )
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    The Microbially Derived Metabolite Indole Attenuates Obesity Associated Inflammatory Processes in Adipocytes and Macrophages

    Thumbnail
    View/Open
    KLEMASHEVICH-DISSERTATION-2016.pdf (2.952Mb)
    Date
    2016-12-07
    Author
    Klemashevich, Cory Lee
    Metadata
    Show full item record
    Abstract
    The human gastrointestinal (GI) tract is colonized by ~10^14 bacteria belonging to ~1,000 species that are collectively termed the intestinal microbiota. Recent studies show that the intestinal microbiota impacts a wide range of functions in the GI tract including development of the immune system, defense against pathogens, and inflammation. Indole is derived from dietary tryptophan from microbial enzymatic activity. Previous work from our laboratory identified indole attenuates indicators of inflammation, increases tight junction resistance and increases colonization resistance in intestinal epithelial cells. This work identifies the effects of indole extend to both adipocytes and macrophages beyond intestinal epithelial cells. Indole attenuates LPS-mediated induction of TNF-α production in RAW264.7 murine macrophages. Additionally, indole also attenuates LPS-mediated MCP-1 expression in 3T3-L1 adipocytes. The inhibition of MCP-1 expression in adipocytes was mirrored by a significant attenuation of bone marrow derived macrophage migration toward MCP-1 and adipocyte conditioned media. Indole correspondingly inhibits macrophage stimulated media induction of MCP-1 in adipocytes. Therefore indole interferes with paracrine signaling between macrophages and adipocytes. Indole is also exhibits agonist and antagonist activity for the AhR. However, the indole-mediated decreases in macrophage chemotaxis towards MCP-1 and in LPS induction of TNF-α production in BMDMs are independent of the AhR. Further, utilizing a novel indole-protein conjugate, we show the effects of indole do not require uptake of indole into the cytoplasm. In addition, this work also demonstrates that indole may signal through the mTOR pathway in macrophages. These studies suggest indole exerts effects on inflammatory processes by altering the mTOR signaling pathway and suggest an alternative mechanism of action to the recently identified effects of indole on the AhR pathway.
    URI
    http://hdl.handle.net/1969.1/159093
    Subject
    indole
    inflammation
    obesity
    microbiota
    mTOR
    AhR
    Collections
    • Electronic Theses, Dissertations, and Records of Study (2002– )
    Citation
    Klemashevich, Cory Lee (2016). The Microbially Derived Metabolite Indole Attenuates Obesity Associated Inflammatory Processes in Adipocytes and Macrophages. Doctoral dissertation, Texas A & M University. Available electronically from http : / /hdl .handle .net /1969 .1 /159093.

    DSpace software copyright © 2002-2016  DuraSpace
    Contact Us | Send Feedback
    Theme by 
    Atmire NV
     

     

    Advanced Search

    Browse

    All of OAKTrustCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsDepartmentThis CollectionBy Issue DateAuthorsTitlesSubjectsDepartment

    My Account

    LoginRegister

    Statistics

    View Usage Statistics
    Help and Documentation

    DSpace software copyright © 2002-2016  DuraSpace
    Contact Us | Send Feedback
    Theme by 
    Atmire NV