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.