"ADAPT" The Adaptation to High Fat Diets Extention

In the past 3 years we have identified a "thrifty-phenotype" characterized in lean men by an
inability to adapt rapidly to a high fat diet and associated with a low maximal VO2 and high
fasting insulin. We hypothesize that the individuals with the "thrifty phenotype" are at
higher risk for becoming obese, and that exercise may be effective in overcoming this
problem.

Several questions remain to be answered regarding the "thrifty" phenotype. First, given the
large interindividual differences, how can we identify those at the highest risk? What are
the distinguishing biochemical, endocrine and environmental characteristics of individuals
that store fat when exposed to high fat diets? This is important because if these
individuals can be easily identified, then dietary interventions can be targeted to this
"at-risk" population.

Second, what is different about the individual with the "thrifty phenotype"? Are there
cellular pathways that are dysregulated in the skeletal muscle of these individuals when
compared to controls? Is the defect intrinsic, i.e. a diminished ability to conserve glucose
and oxidize fat in skeletal muscle or alternately, is the phenotype due to environmental,
and dietary factors such as inactivity and energy excess?

To answer these questions, we have planned a three-year project that aims to:

- Characterize the biochemical, endocrine, anthropometric and environmental
characteristics of individuals with the "thrifty" phenotype.

- Identify the signaling pathways in skeletal muscle that are dysregulated in individuals
with the "thrifty" phenotype through mRNA expression profiling in skeletal tissue.

- Determine the role of environmental factors such as inactivity and caloric intake vs.
intrinsic (genetic) factors in the "thrifty" phenotype.

Inclusion Criteria:

- Both genders and all races will be invited to participate

- Women will be asked to participate in the follicular phase of the menstrual cycle as
determined by menstrual history and a negative pregnancy test will be recorded prior
to participation

- BMI > 19 and < 35

- Age 18-30 Exclusion Criteria

- Smokers

- Unwilling or unable to abstain from alcohol consumption and caffeine consumption
prior to testing and laboratory

- Significant renal, hepatic, endocrine, pulmonary, cardiac or hematological disease

- Pregnancy

- Corticosteroid use in previous two months

- Chronic use of anti-diabetic, anti-hypertensive, or other medications known to affect
fat metabolism

- Use of Depo-Provera, hormone implants or estrogen replacement therapy

- Irregular menstrual cycles

- Post-menopausal women

- Weight gain or loss of > 3kg in the last 6 months

For the MRI, the following exclusion criteria apply:

- Individuals who have a heart pacemaker, defibrillator, or non-removable hearing aid

- Individuals with any clips or metal plates in their head

- Individuals who have any artificial limbs or prosthetic devices

- Individuals who were ever injured by a metallic foreign body which was not removed

- Individuals, who wear braces on their teeth, have non-removable false teeth, or
removable bridgework