Current Research Projects

Developmental signals that regulate body fat distribution

White adipose tissue is an endocrine organ that dynamically expands and contracts to meet the metabolic demands of the organism. It is found in the subcutaneous layer and distinct intra-abdominal depots. Excess abdominal fat is associated with insulin resistance, type 2 diabetes, and cardiovascular disease. In contrast, expansion of subcutaneous white adipose tissue depots is associated with normal insulin sensitivity and reduced incidence of obesity-linked conditions including ectopic fat deposition, hepatic steatosis (fatty liver), and type 2 diabetes. We are interested in transcriptional pathways that specify the patterning of white adipose tissue depots in normal development and obesity. These projects will ultimately explore pathways and signals that dictate the selective expansion of depot-specific fat cells.

Immunology of adipose tissue expandability

Chronic, low grade inflammation in white adipose tissue contributes to the metabolic dysfunction and insulin resistance that precedes T2DM. However, recent work challenges the idea that all immune responses are deleterious to adipose tissue. For instance, a unique population of Foxp3+CD4+ regulatory T cells (Tregs) that function to counteract excess immune response is markedly reduced in adipose tissue of diabetic mice and humans. We discovered Treg infiltration within subcutaneous white adipose tissues generates anti-diabetic effects in mouse models of insulin resistance and obesity. Our current work tests the hypothesis that Tregs in subcutaneous white adipose tissue allow ‘healthy’ fat mass to expand in the face of chronic dietary stress. If our hypothesis is true, we believe it’s possible to leverage the immune system as a tool to maintain insulin sensitivity and manage the co-morbidities of obesity. Ongoing projects align immunology and energy balance studies to understand how the metabolic symbiosis between Tregs and fat cells control subcutaneous adipose tissue expandability during chronic environmental (i.e. dietary) challenge.