Increased Adiposity Risk after Prenatal Alcohol Exposure

Univ Of North Carolina Chapel Hill, Chapel Hill NC

Investigators

Linked publications & trials

Abstract

? DESCRIPTION (provided by applicant): Fetal Alcohol Spectrum Disorder (FASD) is no longer just the largest preventable cause of neurodevelopmental disability. Children with FASD have inappropriate feeding behaviors and overconsume calories and sugar. They also appear to have an increased obesity risk at adolescence. The long term metabolic consequences and underlying mechanisms of this obesity risk are understudied and unknown. Previous animal models of PAE also identify increased adiposity and focus on dysregulation of glucose metabolism, but alcohol affects many pathways and organ systems and there are likely multiple mechanisms by which PAE increases obesity risk. This application tests the hypothesis that dysregulation of lipid metabolism contributes to the increased adiposity of PAE. I will investigate this hypothesis using a mouse model of gestational binge alcohol exposure and study the mechanism underlying this increased adiposity risk after PAE. Aim 1a uses indirect calorimetry to quantify how PAE affects systemic energy balance, as well as the animal's ability to adapt its lipid and glucose metabolism in response to high dietary lipid and carbohydrate challenge. Aim 1b investigates how PAE alters the action of key proteins and signals that regulate lipid metabolism and fate. Taken together, these findings form the foundation for a future K-award application that will detail these mechanisms at the cellular and molecular level. This work will substantially expand our understanding of how PAE increases risk for obesity and later life metabolic disease, and will generate future hypotheses regarding its mechanism and treatment. Because elevated adiposity increases chronic disease risk and reduces quality of life, it is important to understand and address issues that preclude individuals with PAE from living a healthy lifestyle.