Steen, Kaylee2017-10-092017-10-092017-06https://hdl.handle.net/11299/190491University of Minnesota Ph.D. dissertation. June 2017. Major: Biochemistry, Molecular Bio, and Biophysics. Advisor: David Bernlohr. 1 computer file (PDF); vii, 171 pages.Obesity has become a growing epidemic that has greatly increased the prevalence of a variety of metabolic syndromes, such as type II diabetes, cardio vascular diseases, and non-alcoholic fatty liver disease. A major factor that links adiposity to systemic metabolic dysfunction is the resident immune cells in the adipose tissue that exhibit enhanced inflammatory and oxidative stress characteristics. In order to uncouple obesity from these diseases, it is paramount to understand the molecular events that control the inflammation associated with the adipose tissue. The expression of the fatty acid-binding protein 4 (FABP4) in macrophages has demonstrated to be a key determinant of inflammation and oxidative stress where ablation of macrophage FABP4 is protective against obesity related disorders. Furthermore, this decrease in macrophage inflammation was shown to be dependent on the upregulation of uncoupling protein-2 (UCP2) and sirtuin-3 (Sirt3). Collectively these proteins maintained mitochondrial and endoplasmic reticulum homeostasis through redox balance and increased levels of intracellular monounsaturated fatty acids. This further lowered the level of reactive oxygen species, cysteine oxidation and inflammatory cytokine production, all of which have been linked to metabolic dysfunction. The work herein provides greater mechanistic insight into the induction of low-grade, chronic inflammation observed with obesity, which ultimately provides exciting potential for new therapeutic targets.enThesis or Dissertation