According to the Center for Disease Control and Prevention, 35.1% of adults over the age of 20 are obese, and the number is on the rise. The obesity epidemic is, in fact, the leading public health concern of modern society as it leads to numerous diseases affecting both adults and children. Despite the importance of fat in human disease, our understanding of the regulation of fat mass is extremely limited. Dr. Matt Rodeheffer, Associate Professor for the Section of Comparative Medicine and Molecular, Cell, and Developmental Biology at Yale University, is elucidating the cellular and molecular mechanisms that regulate fat mass and contribute to the development of diseases associated with obesity, such as diabetes, cancer, and heart disease. Therefore, his research helps understand why the population is becoming so obese, and furthermore, how we can prevent obesity in the future.

Dr. Rodeheffer’s education-centric research lab is dominated by “dedicated graduate students and overachieving undergraduates.” Therefore, in a collaborative effort, he and his team are making strides in uncovering why obesity has become so prevalent in modern society. Because obesity and metabolic disease arise from complicated physiological interactions, his team is especially dedicated to understanding how fat mass is regulated within the body. Although this approach is time consuming and costly, it yields more relevant discoveries than solely studying isolated cells outside the body, which has been the dominant method over the last several decades. In fact, in the last few years, Dr. Rodeheffer and his team have developed a host of novel methods and materials for studying fat in the body that they are now applying to understand how diet, sex, and age affect the growth and maintenance of fat.

Current research includes:

• Fat Stem Cells: As fat cells are post-mitotic, new fat cells are produced by the proliferation and differentiation of fat stem cells. However, the identity of these stem cells remained elusive until recently, when Dr. Rodeheffer’s lab identified the fat stem cells. They have since characterized the cellular pathway of adipogenesis in vivo and have identified a molecular pathway that leads to increased fat cells only in obesity. These findings open the door for their current studies of how fat cells form during normal development and how the food we eat can lead to obesity.

• The Fat Cell Setpoint: Despite the dynamic nature of fat mass, the number of fat cells is tightly regulated. During normal development, a ‘setpoint’ of fat cell number is established. In obesity, both the size and the number of fat cells increase, establishing a new, higher setpoint. When weight is lost, the fat cells shrink, but the number of fat cells remains increased, potentially making it harder to maintain weight loss. Dr. Rodeheffer is trying to understand how to establish a lower setpoint, and furthermore, if it is possible to decrease a setpoint after it has already been established.

• Obesity Rates: Dr. Rodeheffer and his team are currently working to determine what factors in our diets contribute to the recent rise in obesity rates. If there are specific components of the diet that are leading to increased fat mass, diabetes and heart disease, his research may lead to new dietary recommendations to prevent obesity as well as novel drugs for treating obesity and other diseases associated with obesity.

• Novel Tools: Dr. Rodeheffer is developing an entire system of assays and novel tools to use to study the regulation of fat mass in vivo. This new approach is helping to understand what the signals of fat are and how our diet and activities affect those signals.