BIOMEDICAL ENGINEERING

Adipose tissue plays a critical role in Type II diabetes and obesity either directly by release of fatty acids or indirectly via secretion of adipokines and cytokines. Since adipose tissue does not have a unique artery (inflow) and vein (outflow), reliable in vivo data across this tissue are limited. Furthermore, the heterogeneity of adipose tissue depots (visceral vs. subcutaneous) makes it difficult to generalize from limited data. An essential complement to experimental studies is mathematical modeling for simulation of adipose tissue metabolism in vivo. Our mechanistic model describes adipose tissue and cellular transport processes and metabolic reactions of many key metabolites within distinct metabolic subdomains. This model is based on a wide range of experimental studies, especially responses to intravenous epinephrine and insulin infusions. Consequently, our modeling studies yield quantitative analysis of control mechanisms and prediction of physiological responses that cannot be measured in vivo. Preliminary data confirm model predictions of differential regulation of triglyceride breakdown. Since our model can predict alterations in metabolism, it can be used to determine critical experiments for specific therapeutic interventions. This model of adipose tissue metabolism will be integrated it into a whole body framework to quantitatively analyze the patho-physiology of insulin resistance and non-alcoholic fatty liver disease.

Host: Professor Gerald Saidel