Obesity and Fatty Acid Flux Comparison Trials

Thirty percent of Americans are obese. Women are more severely affected than men.
African-Americans are more severely affected than Caucasians.

To understand the metabolic consequences of obesity, it is essential to know the rate at
which free fatty acids (FFA) are released from adipose tissue. Circulating FFA contribute to
the complications of obesity particularly diabetes and heart disease. As there are sex and
race differences in the prevalence of all these conditions there may be sex and race
differences in FFA flux. FFA flux represents the rate at which FFA circulate. FFA flux is the
result of three processes going on at the same time, (1) the rate FFA are released from
adipose tissue, (2) the rate circulating FFA are used for energy, and (3) the rate FFA leaves
the circulation to re-enter adipose tissue. No data is available on whether sex and race
differences in FFA flux exist. Further, when comparing subjects of different size, sex and
race, it is unknown whether FFA flux should be corrected for lean body mass or resting energy
expenditure.

To determine if there are sex and race differences in FFA flux and to ensure adequate
enrollment of both African American and Caucasians, this investigation is a collaborative
effort between the National Institutes of Health (NIH) in Bethesda, Maryland and the Mayo
Clinic in Olmsted County, Minnesota. The greater Washington, DC, metropolitan area, where NIH
is located, has a large African-American community whereas over 90 percent of residents of
Olmsted County are Caucasians. Therefore, sex differences in FFA flux in African Americans
will be mainly studied at the National Institutes of Health. Sex differences in FFA flux in
Caucasians will be mainly studied at the Mayo Clinic. But, to confirm the ability to combine
data from two different sites, some Caucasians will be enrolled at NIH and some African
Americans will be enrolled at the Mayo Clinic. The results of the two studies will be
combined to determine if there are race differences in FFA flux.

At NIH, 50 African-Americans (25M, 25W, age range 18-49 years) and 14 Caucasians (7M, 7W age
range 18-49 years) will be enrolled. Equal numbers of normal weight, overweight and obese
subjects will be recruited. As outpatients, participants will be placed on weight maintaining
diets for two weeks and then admitted for a two-day hospital stay. On each in-hospital
morning, resting energy expenditure will be measured and stable isotopes infused to measure
FFA flux. Stable isotopes are naturally occurring forms of elements, which are safe and
non-radioactive.

From the study of African-Americans at NIH it will be possible to determine if (a) the rate
of FFA release in African-Americans is more highly related to lean body mass or to resting
energy expenditure, and (b) if there is a sex difference in this relationship. Then as
described above, the results from the Mayo Clinic and NIH will be combined to determine if
there are race differences in the FFA flux.

- INCLUSION CRITERIA - Population:

A total of 134 subjects, age range 18 to 49 will be recruited.

- 64 African-Americans (32 men, 32 women)

- 56 Caucasians (35 men, 35 women)

Within each racial group equal numbers of normal weight, overweight and obese subjects will
be recruited.

African-Americans: Individuals will be considered to be African-American if they
self-identify as African-American and were born in the United States. Further they must
describe both parents as being African-American and born in the United States.

Age: We will recruit subjects between the ages of 18 and 49 years.

Weight: Enrollees must weigh less than 136 kg (300 lbs) and have a BMI less than 36
kg/m(2).

Screening Blood Work: To enroll subjects must have normal hemoglobin levels, electrolyte
panel and normal kidney, thyroid and liver function tests.

Hysterectomy: Women who have had hysterectomies may participate as long as they are less
than or equal to 49 years of age and have normal gonadotropin levels.

Weight and Exercise Regimens: Subjects must report that they have been weight stable for at
least 3 months and will not initiate a rigorous exercise regimen during participation in
the study.

EXCLUSION CRITERIA:

Age: As above, subjects less than 18 years or greater than 49 years will not be enrolled.

Weight: Subjects greater than 136 kg (300 lbs) or BMI greater than 36 kg/m(2) will not be
enrolled.

Medications: Subjects taking medications that are known to affect the parameters under
investigation will be excluded. Some examples of such medications are: oral contraceptives,
depoprovera, antihyperglycemic medications, antihypertensives, hypolipidemics, steroids or
antiobesity agents.

Medical conditions, specifically: Diabetes, Hypertension and Hyperlipidemia.

Breastfeeding: Women who are breastfeeding or have an infant less than four months of age
will be excluded.

Pregnancy: Pregnant women will be excluded from participating.

Minority Status other than African-American: After the sample size necessary to achieve
clinically relevant data is calculated, the plan is to seek permission from the IRB to
expand this study by the enrollment of other minorities.