Stephen R. Farmer

Obesity has now reached pandemic proportions, resulting in dramatic increases in the occurrence of its associated disorders including diabetes and cardiovascular disease. Understanding the processes and metabolic perturbations that contribute to the expansion of adipose depots accompanying obesity is critical for the development of appropriate therapeutics. Expansion of white adipose (WAT) tissue depots particularly the intra-abdominal depots contribute to insulin resistance and inflammation that lead to type 2 diabetes, whereas brown adipose (BAT) resists expansion because it oxidizes lipids and, consequently, it is associated with an healthier phenotype.  Our studies are focused on identifying the mechanisms regulating the formation and function of white and brown adipocytes (fat cells) using a variety of experimental approaches including overexpression and knock down of specific nuclear factors that we consider to be likely regulators of these processes in cells in culture as well as in mice. At present our focus is on nuclear factors that modulate the activity of the two principal regulators of adipogenesis (fat cell differentiation) peroxisome proliferator-activated receptor gamma (PPARg) and CCAAT/enhancer binding proteins alpha, beta and delta (C/EBPs). We are particularly interested in identifying the factors regulating commitment of mesenchymal progenitors to the adipogenic lineage and are adopting a variety of approaches to achieve this goal, which includes gene profiling to discover novel regulators as well as investigating the role of selected candidate genes.