Matthew Rodeheffer

Obesity, which is defined as an increase in white adipose tissue (WAT) mass, results when energy intake exceeds energy expenditure, resulting in the storage of excess energy in the form of lipid. Obesity in the United States and other industrialized nations has increased rapidly over the last thirty years and today 65% of the adult population in the U.S. is overweight with more than 30% of the population meeting the criteria for obesity. As the weight of the nation has increased, so have the incidences of many obesity-linked disorders, such as diabetes, atherosclerosis and certain types of cancer. Despite an increase in white adipose tissue (WAT) mass being the defining characteristic of obesity, we understand little of the cellular and molecular mechanisms that regulate WAT mass in vivo.

WAT is complex tissue that is composed of several subcutaneous and visceral depots pertinent to the study of obesity. The differential accumulation of excessive WAT in specific depots is associated with different risks of developing diabetes and other obesity-associated pathologies. However, the cellular and molecular mechanisms that control WAT mass in distinct depots is not well understood. Therefore, establishing the differences in cellular and molecular events that regulate WAT mass in separate WAT depots will lead to a better understanding of obesity and how excessive WAT leads to the development of secondary pathologies.

The excessive accumulation of WAT in obesity results from an increase of both adipocyte size (hypertrophy) and number (hyperplasia). Since mature adipocytes are post-mitotic, they are generated from the proliferation and differentiation of adipoctye precursor cells. We have recently identified adipocyte progenitors and preadipocytes in vivo, allowing us to directly study the cellular and molecular mechanisms that control adipocyte progenitor contribution to WAT mass in vivo. We hypothesize that by identifying the initiating signals that regulate the tissue-intrinsic control of WAT mass in specific depots we will be able to determine the mechanisms that integrate WAT with other tissues in the body to regulate metabolism and energy balance.

We are currently studying the WAT-intrinsic mechanisms of WAT mass increase at the onset of obesity and during the establishment of normal WAT mass during development in mice. We are also working towards identifying adipocyte progenitor cells in human WAT and other tissues. We are also interested in studying how WAT dynamics differ between genders and how they change during ageing. Identifying molecular mechanisms that regulate WAT mass in these different contexts will lead to the development of directed therapeutics for the treatment of obesity and obesity-associated pathologies, such as diabetes and heart disease.