Mechanisms of the Effect of Physical Activity on the Adaptation to a High-Fat Diet

A high fat diet is linked to weight gain and obesity. An adjustment to the acute exposure to
high fat diet is not abrupt and takes time. In a previous study from our laboratory, it has
been shown that high level of physical activity can accelerate the adaptation to a high fat
diet by increasing fat oxidation. In this study we will determine the mechanism involved in
this adjustment. Our hypotheses are:

1. High fat diets decrease skeletal muscle glucose metabolism and decrease mitochondrial
biogenesis through the upregulation of PDK4 and downregulation of PGC1α; increased
physical activity will prevent these deleterious effects.

2. A high fat diet will increase hepatic and skeletal muscle lipid; increased physical
activity will prevent these deleterious effects.

3. These effects are more pronounced in individuals with a low mitochondrial content

Inclusion Criteria:

- Both genders and all races will be invited to participate

- BMI > 19 and < 35 kg/m2

- Age 18-35

- 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

- Willing and able to walk on a treadmill at a pace of 3 mph at 3%grade for 3-4
hours/day for 3 consecutive days

- Willing to eat only and all foods provided by Pennington for 9 days on 2 occasions
(18 days)

- Willing to stop alcohol consumption for the duration of the study

- Able come to Pennington for meals and tests for 20 days 12 of these inpatient.

Exclusion Criteria:

- Significant renal, hepatic, endocrine, pulmonary, cardiac or hematological disease
(for the consent form you will have to use kidney, liver, etc )

- You abuse alcohol or illegal drugs or are unable to avoid alcohol or caffeine prior
to testing

- Smokers

- Unable or unlikely to eat all and only food provided by the PBRC metabolic kitchen.

- Pregnant or planning to become pregnant

- 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

- Unable or unwilling to perform treadmill walking at the required speed and incline to
achieve 1.8*RMR

- History or family history of blood clots deep vein thrombosis or pulmonary embolism)

- Poor circulation, bypass operation on legs, blood coagulation disorders, diagnosed
peripheral arterial or vascular disease, cramping pain in your muscle during exercise
or nerve damage in your legs.

- You had major surgery on the abdomen, pelvis or legs within previous 3 months.

- You have cancer

- You have rheumatoid disease/ walking or joint problems

- You are claustrophobic

- You are depressed or have an eating disorder

- You demonstrate a style of interpersonal relationships that would inhibit successful
completion of the study

For the MRS / 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 with bridgework held in place by magnets