Pranav Balasubramanian
Pronouns: He/Him
Research Mentor(s): Robert O’Rourke
Research Mentor School/College/Department: Surgery / Medicine
Program:
Authors:
Session: Session 7: 4:40 pm – 5:30 pm
Poster: 44
Abstract
This study aimed to delineate the metabolic phenotype of adipocytes associated with human diabetes (DM) and investigate the regulatory influence of the ECM on adipocyte metabolism. Adipose tissue samples were obtained from obese patients undergoing bariatric surgery and subjected to various culture methods, including 2D cultures, hydrogel cultures, and an innovative in vitro model utilizing decellularized adipose tissue ECM repopulated with human adipocytes. Visceral and subcutaneous adipose tissues collected during bariatric surgery were utilized for metabolic assays such as glucose uptake and lipolysis. The initial investigation focused on elucidating the adipocyte-ECM interplay by pairing ECM from both diabetic (DM) and non-diabetic (NDM) patients with adipocytes from corresponding groups. The findings were that NDM ECM demonstrates potential in rescuing metabolic dysfunction in DM-associated adipocytes, whereas DM ECM imparts features of metabolic dysfunction to non-diabetic adipocytes. Subsequently, the study sought to uncover the mechanisms underlying ECM-mediated regulation of adipocyte glucose uptake, revealing that advanced glycation end products (AGEs) of ECM proteins, particularly collagen, impede adipocyte glucose uptake through Rho GTPase pathways. The findings portrayed an increase in AGE in DM patients as well as reduced glucose uptake Finally, a mechanical perspective was employed to test two different densities of the ECM that affect adipocyte metabolism. The findings demonstrated that increased ECM density correlates with decreased lipid accumulation within adipocytes and therefore contributes to decreased glucose uptake. These findings propose the ECM as a viable target for manipulating adipose tissue metabolism in a disease-specific manner.
