Date of Award

Fall 2019

Document Type

Open Access Dissertation

Department

Biomedical Engineering

First Advisor

Robert M. Gower

Abstract

Despite available treatment options, the number of people afflicted by type 2 diabetes has steadily risen for decades. Nearly 90% of the diabetic population also suffers from obesity and the link between the two diseases is undeniable. Characterized by rapid expansion of the adipose tissue and improper lipid storage, the mishandling of lipids by adipose tissue promotes the diabetic state. Excess lipids, unable to be properly stored, build up in peripheral tissues promoting insulin resistance and type 2 diabetes. Therapeutic strategies designed to address adipose tissue lipid handling could represent a promising treatment strategy for obesity associated type 2 diabetes. Here we investigate the use of polymer scaffolds made of poly(lactide-co-glycolide) as a way to engineer adipose tissue lipid metabolism. Implant of scaffolds into the epididymal adipose tissue of mice leads to glucose and lipid utilization and is attributed to the host response to the material. This lipid oxidizing effect is enhanced by incorporating resveratrol into the polymer scaffolds. Importantly, implant of scaffolds protects mice against fat gain and insulin resistance in a mouse model of obesity associated type 2 diabetes. Finally, we demonstrate the ability of scaffolds combined with healthy dietary changes to reverse insulin resistance in a mouse model of obesity associated type 2 diabetes. Taken together, this work demonstrates promise for tissue engineering strategies designed to address adipose tissue lipid handling as a platform to treat obesity associated type 2 diabetes.

Rights

© 2019, Michael A. Hendley

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