Molecular, Cellular, and Genetic Characterization of Human Adipose Tissue and Its Role in Metabolism

More than ever before, people are eating more calories from food than what they are burning
off through exercise and other activities, and this imbalance is causing the rising rates of
obesity and diabetes in the US and throughout the world. The different types of body fat are
central players in this process. The white fat stores excess calories coming from food, while
brown fat also known as brown adipose tissue, or BAT consumes the energy from food to
generate heat. This important process in BAT is achieved through the action of a special
protein found only in BAT, called uncoupling protein 1 (UCP1).

Scientists used to believe that BAT was important only in small animals and human infants,
but it was recently discovered by us and others that in response to mild cold exposure, adult
human BAT (hBAT) consumes more glucose by weight than any other tissue . In addition, human
BAT may also combat weight gain by becoming more active in the setting of increased food
consumption. This phenomenon has already been demonstrated in mice and rats, and its presence
suggests that activation of human BAT could be used as a safe treatment for obesity and
metabolic disease. Finally, emerging evidence indicates that human BAT may be an endocrine
organ, which means that it releases hormones into the blood and regulates other organs of the
body as well, including skeletal muscle, liver, and the insulin-releasing pancreatic
Beta-cell.

If we are going to understand how hBAT functions in the body physiology and use its
calorie-burning ability to treat illnesses of metabolism such as diabetes, we will need to
approach the challenge using several different methods. One key reason is that BAT is not
easy to find in the body, and the cells that make it up are different depending on where they
are and what the body needs. Brown fat is composed of at least two known types of distinct
cells, termed constitutive /brown and inducible /beige; and there are also white fat cells in
varying proportions. Given that there is currently no known way to estimate the amount of
brown fat in the body from a simple blood test, our lab group has successfully relied on
collecting small amounts of fat from the site of surgery in patients who are already
undergoing clinically indicated procedures. Information obtained from these fat tissues has
addressed questions related to (a) how brown fat cells develop from immature stem cells; (b)
what genes are active; and (c) how many calories the brown fat can burn. These earlier
studies have also provided the preliminary cells necessary for establishing long-lasting
human brown and white cells that can be grown indefinitely in the laboratory. Despite this
progress, much remains unknown about the functional differences between brown and beige fat
cells and how these could affect metabolism in humans of different age, sex, and genetic
backgrounds, as well as the changes seen in the brown fat cells in different illnesses. The
goal of this study is to address these and related questions.

- INCLUSION CRITERIA:

- Male or female

- Any ethnicity

- 18 years or older

- For supraclavicular or dorsocervical adipose biopsy: 18F-FDG PET/CT Scan images
available in the CRC PACS system (performed as part of separate protocol)

EXCLUSION CRITERIA:

- Currently taking blood thinning or anti-inflammatory medications including
anti-platelet or antithrombotic medications.

- Pregnancy

- History of pacemaker, metallic heart valves, aneurysm clip, pedicle screws, metallic
foreign body in eye, or other metallic implant only if using fusion technology for the
biopsy procedure.

- Psychological conditions including (but not limited to) clinical depression, bipolar
disorders, or forms of mental incapacity that would be incompatible with safe and
successful participation in this study.

- Addiction to alcohol or substances of abuse within the last 5 years; current use of
drugs or alcohol (CAGE greater than or equal to 2)