Obesity is associated with a spectrum of metabolic diseases, such as hypertension, diabetes, dyslipidemia, and many types of cancer, which together contribute to the leading causes of morbidity and mortality. 1 in 3 adults in this country are obese, accumulating health care cost upwards of 100 billion dollars a year. While there appears to be a clear overlap between obesity and the development of metabolic diseases, there also exists an interesting subset of population where obese individuals are metabolically healthy. This begs the question, how does adipose tissue contribute to the development of co-morbidities, and what underlying differences exist to explain why some obese individuals seem to be protected from these effects?
The location where excess fat is stored is strongly correlated with the likelihood of developing metabolic disorders. Obese individuals with increased visceral fat are characterized by low-grade chronic inflammation and are much more likely to develop comorbid conditions, while obese individuals with increased subcutaneous fat are less likely to develop these sequelae. If we probe further, down to the cellular level, we find that there are a variety of types of fat cells which are present in differing compositions across fat depots. White adipocytes store energy in lipid droplets and can contribute to inflammation in the setting of obesity. Brown adipocytes are rich in mitochondria and can dissipate energy through adaptive thermogenesis, with anti-obesity and anti-diabetes effects. There is a third type of fat cell called a beige adipocyte. These cells are embedded within adult white adipose depots and can be activated by cold, sympathetic input, or other stimuli to dissipate energy like brown adipocytes. Recent work has shown that the phenotype of fat cells is regulated by a transcriptional coregulatory protein PRDM16, which when deleted results in an ablation of beige fat and more unhealthy visceral-like fat. We are now focused on further dissecting the key molecular controls governing fat cell phenotype with the ultimate goal of engineering healthier fat.