A mathematical model of the immune system's role in obesity-related chronic inflammation

Toby Shearman

Obesity is quickly becoming a pandemic. The low-grade chronic in ammation associated with obesity leads to health risks such as cancer, heart disease, and type 2 diabetes mellitus. To better understand the progression of obesity- related chronic in ammation, mice were fed either a high fat or low fat diet over 140 days. At days 0, 35, 70, and 140, the percentages of macrophage subsets, CD4+ T cells, and regulatory-T cells in ltrating the intra-abdominal white adipose tissue (WAT) were examined. Monocyte chemoattractant protein-1 (MCP-1) mRNA expression in WAT was also quanti ed. Additionally, glucose- normalizing ability was examined by administering peritoneal glucose tolerance tests. This research was conducted during a ten-week research experience for undergraduates. A group of eight undergraduate students participated: Pablo Daz, Michael Gillespie, Justin Krueger, Jos Prez, Alex Radebaugh, Toby Shearman, Garret Vo, and Christine Wheatley. I continued this research independently during the Fall 2008 semester. The REU site was sponsored by NSF and hosted at the Interdisciplinary Center for Applied Mathematics and Virginia Bioinformatics Institute at Virginia Tech.

A system of ordinary differential equations models this system. The model consists of 8 differential equations, has 25 parameters, and has 1 forcing function. While I played an integral role in the development of the model as a whole, my major individual contribution was characterizing the model. Tools I used to characterize the model include parameter estimation and sensitivity analysis. Based on the data provided, the system describes the growth of adipocyte size and chronic in ammation over 105 days beginning at day 35, which is approximately when the adipose cells become hypertrophic. The model shows that without intervention, chronic in ammation escalates and the related health problems persist.