Brown Fat and Cardiovascular Health: Genetic Determinants and Molecular Mechanisms

European Coordinator:
  • Sadaf FAROOQI, University of Cambridge (UK)
North American Coordinator:
  • Robert GERSZTEN, Beth Israel Deaconess Medical Center (USA)
Members:
  • Paul COHEN, Rockefeller University (USA)
  • Mariona GRAUPERA, Bellvitge Biomedical Research Institute (Fundació Institut d’Investigació Biomèdica de Bellvitge) (Spain)
  • Yuval ITAN, Icahn School of Medicine at Mount Sinai (USA)
  • Tayfun OZCELIK, Bilkent University (Turkey)
  • Thomas WANG, UT Southwestern Medical Center (USA)

Obesity is one of the most urgent health problems facing humanity. Over 650 million adults worldwide are obese, and in some countries obesity rates are approaching 50%. Excess body weight significantly increases the likelihood of developing type 2 diabetes, hypertension, and elevated cholesterol. These conditions are major risk factors for cardiovascular disease, the leading cause of death in the world, and these numbers highlight the critical and unmet need to develop therapies to break the link between obesity and disease. Obesity is defined by an excess of body fat, which is comprised of white and brown fat. While white fat stores energy, contributing to obesity and its complications, brown fat holds great potential as a therapeutic target, due to its ability to burn energy, resulting in metabolic benefits. By studying a large human cohort, we have discovered that the presence of brown fat is associated with significantly reduced odds of type 2 diabetes, hypertension, and coronary artery disease. These novel findings in humans serve as the foundation for studies in humans and mouse models to identify genetic determinants of brown fat and understand how it conveys its benefits. Here, we have formed a team of eight scientists and physicians from the United Kingdom, United States, Canada, Spain, and Turkey with distinct and complementary expertise. The goal of our highly interdisciplinary proposal is to determine the basis for the metabolic and cardiovascular benefits of brown fat. We will achieve this goal through three aims: (1) investigating genetic regulation of brown fat function, (2) studying the cardiovascular and metabolic benefits conferred by brown fat, and (3) identifying effectors and circulating biomarkers of brown fat function. This research has the potential to identify entirely new therapeutic targets to disrupt the connection between obesity and associated cardiovascular and metabolic diseases.