Engineering Biomaterial Properties to Modulate Adipocyte Phenotype

Purdue University, West Lafayette IN

Investigators

Abstract

The number of people in the US that are classified as obese is almost 50% of the population, and that number is expected to rise. Obesity contributes to a state of continuous inflammation in fat tissue, and this inflammation increases the risk factor for conditions such as heart disease, type 2 diabetes, and stroke. Although there is a growing epidemic of obesity, there is limited understanding of how the support material outside of the cell affects the disease state of fat cells. This project investigates the effect of the tissue components and stiffness on the contributing response of fat cells toward inflammation. This knowledge will allow the team of investigators to make tissue mimics that can be used to develop therapies to treat obesity and the inflammation that occurs. This research will be used to recruit students from underrepresented groups and will provide multidisciplinary training in biology, biochemistry, and materials engineering. Outreach activities include developing new laboratory modules for female high school students who attend programs hosted by the Women in Engineering Program at Purdue University. During obesity, hypertrophic adipocytes secrete pro-inflammatory cytokines that can cause changes in the extracellular matrix (ECM) and contribute to a host of disease conditions. Recent studies show that the composition of the ECM can be used to cause normal adipocytes to transition into a diseased phenotype. Conversely, the ECM can be used to rescue adipocyte dysfunction and revert them to a healthy phenotype. Experiments described herein will examine the interactions between the biochemical composition and the biophysical properties of the ECM and their effect on adipocyte dysfunction. The research begins by defining the effect that hyaluronic acid avidity has on obesity-related adipocyte dysfunction (Objective #1). Next, the effect that stress relaxation and stiffness have on adipocyte dysfunction will be determined (Objective #2). Finally, the interplay between ligand-induced avidity, stress relaxation, and stiffness have on adipocyte dysfunction will be evaluated in order to understand the weighted contribution that each factor plays (Objective #3). Taken together, this work will show how changes in the microenvironment provide cues that guide adipocyte function and will establish a defined model to better understand drivers of obesity. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.