Modeling effects of sustained bodyweight forces on adipose tissue microstructures and adipocytes in diabesity

Obesity is an epidemic associated with several serious chronic diseases including type 2 diabetes and is characterized by increased fibrosis as a result of excessive deposition of extracellular matrix (ECM) proteins. Specifically, the interlobular septa thickens, and the ECM fibers become denser. In order to study these pathophysiological processes, we developed finite element models of the adipose tissue, simulating lean and obese states, to better understand the effect that forces applying on the tissue have, on the cells. We revealed that the ECM and the interlobular septa has a protective effect on the cells in healthy state. However, an unhealthy, fibrous tissue provides a stiffer microenvironment for the cells (538Pa in obese vs. 323Pa in lean) which may affect cell fate and phenotype through the vicious cycle mechanism in which static cell deformations promote more adipogenesis. This potentially causes altered functionality of the adipose tissue, inflammation, impaired metabolism, and altered responsiveness to signals.