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• W49278400 abstract "Human obesity is increasing globally at an impressive rate. The rise in obesity has led to an increase in diseases associated with obesity, such as type 2 diabetes. A major prerequisite for this disease is the development of insulin resistance in the muscle and adipose tissues. Interestingly, experiments in rodent models suggest that adipocytes and macrophages can profoundly influence the development of insulin resistance. Accordingly, the number of adipose tissue macrophages increases substantially during the development of obesity. Numerous research models have demonstrated that macrophages promote insulin resistance by secreting cytokines, like TNFα, which impair whole body insulin sensitivity and adipose tissue function. Additionally, enhancements of murine adipose function, particularly glucose disposal, prevent the development of insulin resistance in mice on a high fat diet. Thus, mechanisms which enhance adipose function or attenuate macrophage inflammation are of interest. Our lab previously identified mitogen activated protein kinase kinase kinase kinase 4 (MAP4K4) as a potent negative regulator of adipocyte function. In these studies, TNFα treatment increased the expression of adipocyte MAP4K4. Furthermore, the use of small interfering RNAs (siRNA) to block the increase in MAP4K4 expression protected adipocytes from some of the adverse effects of TNFα. Because MAP4K4 is a potent negative regulator of adipocyte function, an understanding of the mechanisms by which TNFα regulates MAP4K4 expression is of interest. Thus, for the first part of this thesis, I characterized the signaling pathways utilized by TNFα to regulate MAP4K4 expression in cultured adipocytes. Here I show that TNFα increases MAP4K4 expression through a pathway requiring the transcription factors activating transcription factor 2 (ATF2) and the JUN oncogene (cJUN). Through TNFα receptor 1 (TNFR1), but not TNFR2, TNFα increases MAP4K4 expression. This increase is highly specific to TNFα, as the inflammatory agents IL-1β, IL-6 and LPS did not affect MAP4K4 expression. In agreement, the activation of cJUN and ATF2 by TNFα is sustained over a longer period of time than by IL-1β in adipocytes. Finally, MAP4K4 is unique as the expression of other MAP kinases tested fails to change substantially with TNFα treatment. For the second part of this thesis, I assessed the role of MAP4K4 in macrophage inflammation in vitro and in vivo . To accomplish this task, pure β1,3-D-glucan shells were used to encapsulate siRNA. Glucan shells were utilized because they are effectively taken up by macrophages which express the dectin-1 receptor and they survive oral delivery. I demonstrate that these β1,3-D-glucan encapsulated RNAi particles (GeRPs) are efficiently phagocytosed and capable of mediating the silencing of multiple macrophage genes in vitro and in vivo . Importantly, oral treatment of mice with GeRPs fails to increase plasma IFNγ and TNFα or alter serum AST and ALT levels. Orally administered GeRPs are…" @default.
• W49278400 created "2016-06-24" @default.
• W49278400 creator A5066765846 @default.
• W49278400 date "2008-01-01" @default.
• W49278400 modified "2023-09-23" @default.
• W49278400 title "Role of MAP4K4 Signaling in Adipocyte and Macrophage Derived Inflammation: A Dissertation" @default.
• W49278400 cites W137414433 @default.
• W49278400 cites W145128978 @default.
• W49278400 cites W1497305679 @default.
• W49278400 cites W1501881225 @default.
• W49278400 cites W1524321743 @default.
• W49278400 cites W152689106 @default.
• W49278400 cites W1532242553 @default.
• W49278400 cites W1534360145 @default.
• W49278400 cites W1538276446 @default.
• W49278400 cites W1580646470 @default.
• W49278400 cites W1582691127 @default.
• W49278400 cites W1585651039 @default.
• W49278400 cites W1595083713 @default.
• W49278400 cites W1604941563 @default.
• W49278400 cites W1605681980 @default.
• W49278400 cites W1611419331 @default.
• W49278400 cites W1647075334 @default.
• W49278400 cites W1648037819 @default.
• W49278400 cites W1649341603 @default.
• W49278400 cites W1657715719 @default.
• W49278400 cites W1697523131 @default.
• W49278400 cites W1712871378 @default.
• W49278400 cites W1764140709 @default.
• W49278400 cites W1773423156 @default.
• W49278400 cites W180238663 @default.
• W49278400 cites W1837570225 @default.
• W49278400 cites W1841050729 @default.
• W49278400 cites W1916491745 @default.
• W49278400 cites W1964093831 @default.
• W49278400 cites W1964241768 @default.
• W49278400 cites W1965371391 @default.
• W49278400 cites W1965680797 @default.
• W49278400 cites W1965853004 @default.
• W49278400 cites W1966543080 @default.
• W49278400 cites W1968336033 @default.
• W49278400 cites W1969597931 @default.
• W49278400 cites W1971762417 @default.
• W49278400 cites W1972499532 @default.
• W49278400 cites W1974033843 @default.
• W49278400 cites W1974500456 @default.
• W49278400 cites W1974599416 @default.
• W49278400 cites W1974651199 @default.
• W49278400 cites W1978568726 @default.
• W49278400 cites W1978625554 @default.
• W49278400 cites W1979428788 @default.
• W49278400 cites W1979598489 @default.
• W49278400 cites W1981261500 @default.
• W49278400 cites W1981614332 @default.
• W49278400 cites W1982944995 @default.
• W49278400 cites W1983046008 @default.
• W49278400 cites W1983072380 @default.
• W49278400 cites W1984665850 @default.
• W49278400 cites W1984903682 @default.
• W49278400 cites W1985982057 @default.
• W49278400 cites W1986168751 @default.
• W49278400 cites W1987120082 @default.
• W49278400 cites W1987617539 @default.
• W49278400 cites W1988330102 @default.
• W49278400 cites W1988870963 @default.
• W49278400 cites W1989024278 @default.
• W49278400 cites W1989829058 @default.
• W49278400 cites W1989973870 @default.
• W49278400 cites W1991401793 @default.
• W49278400 cites W1991795789 @default.
• W49278400 cites W1992308584 @default.
• W49278400 cites W1992496199 @default.
• W49278400 cites W1994376108 @default.
• W49278400 cites W1994603967 @default.
• W49278400 cites W1995448901 @default.
• W49278400 cites W1995744610 @default.
• W49278400 cites W1996120614 @default.
• W49278400 cites W1996163490 @default.
• W49278400 cites W1996609303 @default.
• W49278400 cites W1996713062 @default.
• W49278400 cites W1996866382 @default.
• W49278400 cites W1998493448 @default.
• W49278400 cites W1999971397 @default.
• W49278400 cites W2000054651 @default.
• W49278400 cites W2000082154 @default.
• W49278400 cites W2002393861 @default.
• W49278400 cites W2003013566 @default.
• W49278400 cites W2003230730 @default.
• W49278400 cites W2004290834 @default.
• W49278400 cites W2004767178 @default.
• W49278400 cites W2004894972 @default.
• W49278400 cites W2005901295 @default.
• W49278400 cites W2007405015 @default.
• W49278400 cites W2008100923 @default.
• W49278400 cites W2008869160 @default.
• W49278400 cites W2009010832 @default.
• W49278400 cites W2009476361 @default.
• W49278400 cites W2009525986 @default.
• W49278400 cites W2009550948 @default.
• W49278400 cites W2010188590 @default.

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