Project Number: 1950-51000-071-02
Project Type: Specific Cooperative Agreement

Start Date: Apr 17, 2009
End Date: Apr 16, 2014

Objective:
1. Define the role and mechanisms of adipocyte death in obesity-associated inflammation and metabolic disorders using genetic and nutritional models of adipocyte growth and death. 2. Determine the role of the macrophage in modulating adipocyte death and associated adipose tissue inflammation using genetically altered animal models. 3. Determine the mechanisms by which alterations in Lipid Droplet (LD) proteins modulate lipolysis and risk of developing metabolic disorders. 4. To determine the role of acyl CoA-synthetase 5 in systemic metabolism.

Approach:
The role of adipocyte death in obesity will be investigated using a combination of transgenic and knockout mouse models and bone-marrow transplantation in mice fed different diets to understand the influence of obesity. In vivo and in vitro studies will investigate glucose and insulin homeostasis complemented by histological, immunohistological, electron microscopic, gene expression, FACS analysis, adipocyte lipolysis and Akt signaling studies. For studies investigating lipid droplet proteins, we will use both adenovirus expression vectors and possibly transgenic animals to determine how alterations in expression and intracellular signaling regulate protein expression, metabolic pathways, and lipolysis in cultured cells and animals. Depending upon which tissue is studied, we will examine lipolysis and protein expression, alterations in cytokine, lipid accumulation, signal transduction pathways, and oxidative gene expression.