The long-term objective of this study is to develop new treatments for obesity and obesity-associated disorders such as diabetes and dyslipidemia. The recent finding of active brown fat depots in adult humans provides an exciting new strategy for the treatment of these diseases. Brown fat is a specialized organ found primarily in small mammals. Brown fat has the unique capability to burn fuel at high rates in order to generate heat. The role of brown fat in mammals is to defend against cold exposure. Human infants have active brown fat deposits located in the intra-scapular region. This brown fat depot regresses with age and it was long thought that adult humans had no brown fat tissue. Recent studies have demonstrated the presence of brown fat activity in adult humans following exposure to cold. Brown fat in adult humans is concentrated in the cervical region and displays some sex-specific differences. Furthermore the size of the depot is inversely correlated with BMI and age of the subjects. This finding has generated intense interest as it opens up the possibility of harnessing brown fat as a means of combating obesity and obesity-related disorders in man. Indeed, maneuvers that activate brown fat in humans have been shown to cause reductions in fat mass.

Much of our understanding of brown fat biology comes from work in mice. Of particular relevance for the treatment of human disease are several findings. First, increasing brown fat activity in mice renders the animals resistant to the development of obesity on a high fat diet. Second, levels of insulin sensitivity are directly related to brown fat activity. Finally, the transcription factor factor PR-domain containing protein 16 (PRDM-16) is crucial for directing the biology of brown fat.

The overall goal of the study is to translate the findings from mouse studies of brown fat into human subjects. This is an important first step in the process of developing brown fat-targeted therapies to treat human metabolic diseases such as obesity and insulin resistance. In view of this the investigators are interested in answering several questions. First, do humans with mutations in PRDM-16 have defects in brown fat activity? Recently, humans with mutations in PRDM-16 were identified and found to have a cardiomyopathy phenotype. The brown fat function in these individuals has not been described. By employing a genetic screen of volunteers the investigators hope to identify subjects in Singapore with defects in PRDM-16. Prior studies in humans suggest that the size of the brown fat depot is inversely correlated with BMI and age of the subjects and that depot size varies between the sexes. In order to eliminate BMI, age and sex as confounding variables the investigators will include male subjects of Chinese race between the ages of 21 and 50 and with BMI greater than 18.5 but less than 30. The investigators will include only Chinese subjects to avoid confounding our initial study with variables that relate to race of the subjects. The identification of human subjects carrying mutations in PRDM-16 will set the stage for further studies that will attempt to several research questions. These include whether humans with PRDM-16 mutations have defects in brown fat and the metabolic consequences for humans with defective brown fat.