@article{Metabolically:2726,
      recid = {2726},
      author = {Hoffman, Alexandria Simone},
      title = {Metabolically Activated Adipose Tissue Macrophages and  Insulin Resistance},
      publisher = {University of Chicago},
      school = {Ph.D.},
      address = {2020-12},
      pages = {95},
      abstract = {Insulin resistance and type 2 diabetes have reached  epidemic levels in the United States. Mouse models have  demonstrated that the increase in inflammatory cytokines  during obesity is a mechanistically linked to insulin  resistance. Adipose tissue macrophages, which accumulate  and become activated during obesity, are a major source of  this inflammation. These macrophages were often thought to  be classically activated. However, studies of adipose  tissue macrophages in humans demonstrate that the human  obese adipose tissue macrophage phenotype is less  straightforward. Our lab demonstrated that these  macrophages exhibit a phenotype distinct from classical  activation and redefined them as metabolically activated.  Here we investigate the association of surface markers of  metabolic activation with insulin resistance in humans. We  use flow cytometry and a host of other parameters to show  that insulin resistance is associated with omental ABCA1  expression independent of changes in inflammation. We also  present an unexpected and strong relationship between ABCA1  expression and omental adipocyte size. These findings  reveal a novel marker associated with insulin resistance in  humans and raise further questions about role of adipose  tissue macrophages in this disease. In our second aim we  present a series of tyrosine kinases that promote metabolic  activation. We also demonstrate that metabolic activation  engages the transcription factor NFB using a mechanism  that is distinct from canonical NFB signaling. These  findings provide new therapeutic targets to treat insulin  resistance through attenuating macrophage activation.  Overall, this work provides insight into the metabolic  activation phenotype at multiple levels and establishes a  foundation to pursue the pathways that drive it. },
      url = {http://knowledge.uchicago.edu/record/2726},
      doi = {https://doi.org/10.6082/uchicago.2726},
}