Atherosclerosis is the principal contributing factor of heart disease, the main cause of death in the US. Together with obesity, the development of these two diseases occurs because of an excessive accumulation of lipids, which also alters the immune system by causing inflammation. Beta-carotene (?-carotene) is a natural pigment synthesized by plants and the main precursor of vitamin A in animals. Vitamin A is crucial for the immune system function and for the development of adipocytes and therefore obesity, but the relevance of ?-carotene and vitamin A on atherosclerosis and obesity is scarce. In humans, even though the levels of ?-carotene in plasma and tissues are high, ?-carotene is hardly detectable in wild-type mouse even after supplementing their diet with large amounts of ?-carotene. Additionally, normal mice do not develop atherosclerosis; therefore, to study the effect of ?-carotene in atherosclerosis and obesity demands special animal models. To overcome these experimental limitations, we have generated, together with our collaborators, a mouse model that mimics the accumulation of ?- carotene and develops atherosclerosis, as occurs with humans. This novel model is essential to understand the role that ?-carotene plays on vitamin A production, and will help us to study these two common human diseases in a ?humanized? animal model. First, we will investigate why the ingestion of ?-carotene is beneficial against the development of atherosclerosis in mice, and how this effect relates to people. Second, we will use our mouse model to study the function that plasma ?-carotene has on immune cells during atherosclerosis and obesity development. Lastly, we will develop a technique to take advantage of the ?- carotene stored in adipose tissue to stimulate the production of vitamin A in adipocytes, which will have beneficial effects on obesity and atherosclerosis. The overall goal of this study is to understand the role of ?-carotene on vitamin A formation in humans by utilizing a specific mouse model. We hope that this approach will help our society to consider ingested and stored ?-carotene as a potential therapeutic strategy to treat atherosclerosis and obesity.
The focus of this project is to study ?-carotene, the precursor of vitamin A, as a therapy to fight heart disease and obesity. Using a specific animal model to mimic ?-carotene metabolism, we will investigate the role this compound has in blood and adipose tissue, where it is present in large amounts.