Increasing evidence has shown that sub-acute inflammation plays important role in the pathogenesis of insulin resistance (IR), type 2 diabetes, and metabolic syndrome. The adipocyte was first thought to be central to this process, largely because the whole tissue was analyzed instead of individual cell types. Yet more recent studies have focused on macrophages in adipose tissue, whose numbers increase as fat mass expands. During my fellowship training, I plan to determine hierarchy and temporal in vivo relationship between adipocytes and macrophage activation in obesity and diet induced IR. I will use mouse models in which NF-kB activity is either activated or inhibited in either adipocytes or macrophages. In addition, I will also profile others cells, such as endothelial cells, dendritic cells, and T lymphocytes. They are present in stromal vascular fraction of AT, and they might also play major roles in obesity and diet induced IR. My hypothesis is that obesity and diet-induced inflammation resembles classical inflammation in which adipocytes are the initiators that lead to increased macrophage content and activation via active participation of endothelial cells and other immune cells. ? ? ?
