EXPLORING THE ROLE OF BRAIN ANGIOGENESIS INHIBITOR 3 (BAI3) IN REGULATING BODY WEIGHT

Abstract

Obesity is a significant public health issue, strongly associated with various metabolic disorders, including type 2 diabetes and cardiovascular disease. Understanding the mechanisms that contribute to obesity is essential for developing effective interventions. One critical area of interest involves G-protein-coupled receptors (GPCRs), which are important in regulating metabolic health. These receptors are known to be involved in critical metabolic functions such as insulin secretion, lipid metabolism, and glucose uptake. The role of the GPCR, brain angiogenesis inhibitor-3 (BAI3), in metabolic regulation has not been fully explored. This dissertation focuses on the known functions of the BAI isoforms (BAI1-3) and presents a novel perspective on how BAI3 may influence whole-body glucose homeostasis. Specifically, I investigate the role of BAI3 in regulating body weight. I hypothesize that BAI3 controls body weight by regulating energy expenditure. To test this, I utilized a whole-body BAI3 knockout model and discovered that BAI3 influences energy expenditure through adaptive thermogenesis in young mice, independent of sex. Building on these findings, I expanded our study to examine how the loss of BAI3 affects diet-induced obesity (DIO) in the context of a high-fat diet (HFD) and its associated metabolic consequences. Genetic studies have linked BAI3 to alterations in body mass index (BMI) and various metabolic traits, and it is known to mediate cAMP inhibition. Based on this, I hypothesize that BAI3 negatively regulates energy balance, potentially worsening overall metabolic health. A series of experiments were conducted to test this hypothesis, and the results highlight BAI3 as a promising target for further investigation into energy homeostasis and metabolic regulation. Future studies should aim to delineate the specific signaling pathways involved in BAI3's metabolic effects and explore the potential for clinical applications of BAI3 modulation in improving metabolic health.