Determining the role of the macrophage GLUT1 transporter and glucose metabolism in obesity-associated inflammation

Obesity and diabetes are the most prevalent metabolic diseases in the United States, afflicting over 60% of the adult population. The immune system contributes to obesity and insulin resistance, which are likely linked to over-nutrition. The adipocyte is more than a static lipid storage unit, and plays a crucial role as an endocrine organ, inducing the recruitment of macrophages to adipose tissue in obesity. Macrophages, specifically pro-inflammatory or M1-polarized, are the immune cells most commonly associated with perpetuating inflammation in adipose tissue through the secretion of inflammatory cytokines. The number of macrophages is increased significantly in obese adipose tissue; the damaged tissue, potentially trigged by hypoxia, may attract macrophages to the site, as M1 macrophages have been observed to form “crown-like structures” (CLS) around dead or dying adipocytes. We reported that GLUT1 is the primary rate-limiting glucose transporter on type I macrophages, thus we hypothesize that GLUT1 is essential in the activation of the pro-inflammatory response of macrophages. To test this hypothesis, quantitative polymerase chain reaction (qPCR) was used to determine the expression of specific genes associated with the pro-inflammatory M1 response in both GLUT1M+ and GLUT1M- bone marrow-derived macrophages (BMDMs) and epididymal white adipose tissue (eWAT) of lean and obese mice. eWAT of GLUT1M+ and GLUT1M- mice fed either a high-fat diet (HFD) or low-fat diet (LFD) was collected to examine the effects of the GLUT1 deletion on diet-induced obesity (DIO). Preliminary data, qPCR results and histologic analysis of CLS in adipose tissue suggest that although macrophage infiltration is occurring, polarization to the pro-inflammatory M1 phenotype is inhibited, resulting in an attenuated inflammatory response. Ultimately, findings from this study yield insight into the contribution of glucose metabolism to macrophage polarization and obesity.Bachelor of Science in Public Healt