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

Study Overview
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Brief Summary
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The study is designed to determine the effect of high physical activity level vs. low physical activity level on the adaptation to a high fat diet.

Detailed Description
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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: 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. A high fat diet will increase hepatic and skeletal muscle lipid; increased physical activity will prevent these deleterious effects. These effects are more pronounced in individuals with a low mitochondrial content

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

Conditions
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Healthy

Intervention / Treatment
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* Other: Physical Activity Level


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>High intensity exercise and high fat diet | Other: Physical Activity Level<br>* High vs. low physical activity during a high fat diet consumption.<br>|
| Experimental: 2<br>Low intensity exercise and high fat diet | Other: Physical Activity Level<br>* High vs. low physical activity during a high fat diet consumption.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the effects of a high fat diet [at both low and high physical activity] on • Sk muscle PGC1α and PDK4 mRNA and protein • Glucose oxidation • Fatty acid oxidation • Hepatic and skeletal muscle lipid • VO2 max • Mitochondr |  | One Year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adaptation to high fat diet, activity, exercise