The Cholesterol Transporter ABCA1 and Cholesterol Accumulation are Key Regulators of Adipose Function in Obesity

Abstract

Obesity now affects over 1/3 of the U.S. adult population, and this number is predicted to grow in the next decades. In addition, obesity, and it’s related comorbidities, cost the U.S. healthcare system roughly $150 billion per year. Central to the development of obesity is adipose tissue mass expansion. During nutritional excess, adipose stores excess energy as triglycerides (TG), which results in adipocyte hypertrophy and fat pad expansion. In addition, adipose is a dynamic endocrine organ that releases a variety of adipokines that affect whole body metabolism. While much research has focused on adipose storage of TG in the past, this dissertation focuses on cholesterol. Adipocytes can account for up to 50% of the body’s free cholesterol storage, but the effect of cholesterol on adipose tissue, and the role of adipose tissue in whole body cholesterol metabolism are relatively understudied. This thesis presents two models to study adipose cholesterol. The first used a non-human primate model to determine the effect of additional dietary cholesterol on adipose tissue depots, and the second uses an adipose specific knock out of ATP Binding Cassette Transporter A1 (ABCA1) to study adipose cholesterol metabolism in mice.