2009 Math Biology Seminar - 07

Speaker: Vipul Periwal

"Dynamics of Adipose Tissue Growth"

Abstract:

Adipose tissue grows by two mechanisms: hyperplasia (cell number increase) and hypertrophy (cell size increase). Genetics and diet affect the relative contributions of these two mechanisms to the growth of adipose tissue in obesity. To address adipose tissue growth precisely, we developed a mathematical model describing the evolution of the adipose cell-size distributions as a function of the increasing fat pad mass, instead of the increasing chronological time. Our model describes the recruitment of new adipose cells and their subsequent development in different strains, and with different diet regimens, with common mechanisms, but with diet- and genetics-dependent model parameters. Hyperplasia is enhanced by high-fat diet in a strain-dependent way, suggesting a synergistic interaction between genetics and diet. Moreover, high-fat feeding increases the rate of adipose cell size growth, independent of strain, reßecting the increase in calories requiring storage. Additionally, high-fat diet leads to a dramatic spreading of the size distribution of adipose cells in both strains; this implies an increase in size ßuctuations of adipose cells through lipid turnover.

Speaker: Will Heuett

"Modeling Metabolism in Pancreatic Beta-Cell Mitochondria"

Abstract:

Pancreatic beta-cells sense the ambient blood-glucose concentration and secrete insulin to signal other tissues to take up glucose. Mitochondria play a key role in this response as they metabolize nutrients to produce ATP and reactive oxygen species (ROS), both of which are involved in insulin secretion signaling. I will present a model of beta-cell mitochondrial respiration, ATP synthesis, and ROS production in response to glucose and fatty acid stimulation, based on available data in the literature and mathematical models derived from first principles. The model explains experimental observations of the non-ohmic rise in the passive proton-leak rate at high membrane potential and its dependence on increased ROS production. It also predicts that glucose-stimulated insulin secretion is inhibited by long-term fatty acid exposure, but can be enhanced by inhibiting uncoupling protein activation and promoting mitochondrial biogenesis. Using glucose and fatty acid profiles from individuals, I will show that there is a negative correlation between the amount of ROS produced per ATP, as predicted by the model, and the individual insulin sensitivities. Finally, I will discuss how the model can be used to predict the c-peptide and insulin secretion rate and provide a quantitative description of beta-cell function for a single individual. Return to seminar page