Browsing by Author "Johnson, Amy R."

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    Metabolic reprogramming through fatty acid transport protein 1 (FATP1) regulates macrophage inflammatory potential and adipose inflammation
    (Elsevier, 2016-07) Johnson, Amy R.; Qin, Yuanyuan; Cozzo, Alyssa J.; Freemerman, Alex J.; Huang, Megan J.; Zhao, Liyang; Sampey, Brante P.; Milner, J. Justin; Beck, Melinda A.; Damania, Blossom; Rashid, Naim; Galanko, Joseph A.; Lee, Douglas P.; Edin, Matthew L.; Zeldin, Darryl C.; Fueger, Patrick T.; Dietz, Brittney; Stahl, Andreas; Wu, Ying; Mohlke, Karen L.; Makowski, Liza; Department of Cellular & Integrative Physiology, IU School of Medicine
    OBJECTIVE: A novel approach to regulate obesity-associated adipose inflammation may be through metabolic reprogramming of macrophages (MΦs). Broadly speaking, MΦs dependent on glucose are pro-inflammatory, classically activated MΦs (CAM), which contribute to adipose inflammation and insulin resistance. In contrast, MΦs that primarily metabolize fatty acids are alternatively activated MΦs (AAM) and maintain tissue insulin sensitivity. In actuality, there is much flexibility and overlap in the CAM-AAM spectrum in vivo dependent upon various stimuli in the microenvironment. We hypothesized that specific lipid trafficking proteins, e.g. fatty acid transport protein 1 (FATP1), would direct MΦ fatty acid transport and metabolism to limit inflammation and contribute to the maintenance of adipose tissue homeostasis. METHODS: Bone marrow derived MΦs (BMDMs) from Fatp1 (-/-) and Fatp1 (+/+) mice were used to investigate FATP1-dependent substrate metabolism, bioenergetics, metabolomics, and inflammatory responses. We also generated C57BL/6J chimeric mice by bone marrow transplant specifically lacking hematopoetic FATP1 (Fatp1 (B-/-)) and controls Fatp1 (B+/+). Mice were challenged by high fat diet (HFD) or low fat diet (LFD) and analyses including MRI, glucose and insulin tolerance tests, flow cytometric, histologic, and protein quantification assays were conducted. Finally, an FATP1-overexpressing RAW 264.7 MΦ cell line (FATP1-OE) and empty vector control (FATP1-EV) were developed as a gain of function model to test effects on substrate metabolism, bioenergetics, metabolomics, and inflammatory responses. RESULTS: Fatp1 is downregulated with pro-inflammatory stimulation of MΦs. Fatp1 (-/-) BMDMs and FATP1-OE RAW 264.7 MΦs demonstrated that FATP1 reciprocally controled metabolic flexibility, i.e. lipid and glucose metabolism, which was associated with inflammatory response. Supporting our previous work demonstrating the positive relationship between glucose metabolism and inflammation, loss of FATP1 enhanced glucose metabolism and exaggerated the pro-inflammatory CAM phenotype. Fatp1 (B-/-) chimeras fed a HFD gained more epididymal white adipose mass, which was inflamed and oxidatively stressed, compared to HFD-fed Fatp1 (B+/+) controls. Adipose tissue macrophages displayed a CAM-like phenotype in the absence of Fatp1. Conversely, functional overexpression of FATP1 decreased many aspects of glucose metabolism and diminished CAM-stimulated inflammation in vitro. FATP1 displayed acyl-CoA synthetase activity for long chain fatty acids in MΦs and modulated lipid mediator metabolism in MΦs. CONCLUSION: Our findings provide evidence that FATP1 is a novel regulator of MΦ activation through control of substrate metabolism. Absence of FATP1 exacerbated pro-inflammatory activation in vitro and increased local and systemic components of the metabolic syndrome in HFD-fed Fatp1 (B-/-) mice. In contrast, gain of FATP1 activity in MΦs suggested that Fatp1-mediated activation of fatty acids, substrate switch to glucose, oxidative stress, and lipid mediator synthesis are potential mechanisms. We demonstrate for the first time that FATP1 provides a unique mechanism by which the inflammatory tone of adipose and systemic metabolism may be regulated.
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    Stranger in the Room: Illuminating Female Identity Through Irish Drama
    (2007-05-23T16:41:31Z) Johnson, Amy R.; Eller, Jonathan R., 1952-
    This thesis centers on a country that has produced some of the greatest and most important English language dramas of the past two centuries. Within this cultural context, this thesis is also about a feminine revival in Irish theatre and how this can be a powerful tool to incite change. Early in history, Irish writers, and specifically dramatists, recreated a type of theatre that captured the true essence of what it meant to be Irish by representing their struggles, frustrations and humor. The Irish talent for storytelling connects back to its Gaelic roots and has remained a constant in the life of a culture that has passed down this art form for centuries. The focus of this thesis is to examine three contemporary Irish plays by prominent playwrights who came to the world of theatre from very different backgrounds. Each play is written by a different hand, yet all share a vital common denominator: the interaction of female character groups – groups that are central to the action of each play. What incited my interest in these three plays – Brian Friel’s Dancing at Lughnasa, Anne Devlin’s Ourselves Alone and Marina Carr’s The Mai – was the playwright’s ability to expose what had been silenced in Irish history for so long. Each female character portrays one important aspect of Irish womanhood that has been tragically understated in the nation’s literature since the death of John Millington Synge: woman’s struggle between what she wants to be and who she is expected to be. These three plays will be scrutinized in terms of three elements of social control contributing to woman’s struggle in Irish society: myth, church and patriarchal tradition.