Training Effects on Skeletal Muscle Fatty Acid Metabolism

Study Overview
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Brief Summary
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We are interested in how skeletal muscle processes fat and how this may affect insulin resistance. This is an important question since insulin resistance predates and predicts type 2 diabetes. We know that if pharmaceutical grade fat is infused into people, they develop insulin resistance. Likewise, we would like to infuse pharmaceutical grade fat into trained subjects, believing that trained subjects will have less insulin resistance, less decline in muscle energy function, and less accumulation of fat metabolites than untrained subjects. For comparing the effects of the pharmaceutical grade fat infusion, we will also have a group of trained and untrained subjects given a control (glycerol) infusion. Glycerol is basically the same as pharmaceutical grade fat infusion without the fat component.

Detailed Description
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We are interested in how skeletal muscle processes fat and its effect on insulin resistance. This is an important question since insulin resistance predates and predicts type 2 diabetes. We know that if pharmaceutical grade lipid is infused into people, they develop insulin resistance. Thus, we would like to infuse pharmaceutical grade lipid into trained subjects, believing that trained subjects will develop less insulin resistance, less decline in muscle energy function, and less accumulation of fat metabolites than untrained subjects. For comparing the effects of the pharmaceutical grade fat infusion, we will also have a group of trained and untrained subjects given a control (glycerol) infusion. Glycerol is basically the same as pharmaceutical grade lipid infusion without the lipid component. Three visits will be required. The first visit will involve measurement of fitness. A second visit will involve measurement of insulin resistance. The third visit will involve an inpatient stay, with a six hour infusion either the lipid or glycerol. Three muscle biopsies (before, during and after) will be take in conjunction with the infusion.

Official Title
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Training Effects on Skeletal Muscle Fatty Acid Metabolism

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: 20% lipid infusion
* Drug: glycerol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Regardless of training status, age range will be from age 18 to 45. We will be limiting the upper age range because increased age is associated with sarcopenia and alteration of fiber type 29 and we would like to limit the confounding effects of age. We will define the lean group by a BMI of < 25 kg/m2. Weight must be stable [+/- 5 pounds] for at least the three months prior to the study for all participants. The untrained subjects must not be engaged in a regular exercise program (< 30 minutes regular exercise over 1 week). The trained subjects should be participating in regular running exercise (> 45 min/day, ≥ 5 days/week) and preferably be currently or recently participating in competitions (within 2 years). Exclusion Criteria: Regardless of training status, subjects must not be on medications that may affect lipid levels, specifically lipid lowering agents, birth control pills or diuretics. The subjects should not be on a high fat diet (> 45% fat) as measured by a screening questionnaire. We will also administer a PAR-Q questionnaire (attached) to establish whether the subject will be safe for exercise testing. - The female subjects must not be pregnant. A pregnancy test will be performed prior to all study visits. If screening TG are > 300 (based on 1st visit results) or fasting glucose > 100 (based on 1st visit results), the subjects will be excluded. If the subject is allergic to eggs (used in lipid emulsions), soybeans(used in lipid emulsions), or lipid emulsions the subject will be excluded from the study. Subjects taking anti-platelet agents (if anti-platelet agent cannot be held for seven days) and subjects taking anticoagulation therapy will be excluded. Subjects with clinically significant medical issues or a history of hematologic (platelets < 100), hepatic (LFTs > 2X nl), renal (Cr > 1.5), pulmonary, or cardiac abnormalities (including abnormal EKG) will also be excluded.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: lipid trained<br>20% lipid infusion in trained subjects | Drug: 20% lipid infusion<br>* 1.5 ml/min for 6 hours<br>* Other names: fat infusion;|
| Active Comparator: glycerol trained<br>glycerol infusion into trained subjects | Drug: glycerol<br>* glycerol infusion (2.25 g/100ml) will be administered at 1.5 ml/min,<br>* Other names: glycerol infusion;|
| Experimental: lipid untrained<br>lipid infusion into untrained subjects | Drug: 20% lipid infusion<br>* 1.5 ml/min for 6 hours<br>* Other names: fat infusion;|
| Active Comparator: glycerol untrained<br>glycerol infusion into untrained subjects | Drug: glycerol<br>* glycerol infusion (2.25 g/100ml) will be administered at 1.5 ml/min,<br>* Other names: glycerol infusion;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Sensitivity as Measured by Hyperinsulinemic Euglycemic Clamp at a Single Time Point (6 Hrs) After Intralipid or Glycerol Infusion | Insulin sensitivity (M value: Glucose infusion rate/kg FFM/min)measured at single time point 6 hours after initiating either intralipid or glycerol infusion) | at 6 hours after starting lipid/glycerol infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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insulin resistance, lipid metabolism, lipid infusion, glycerol infusion, skeletal muscle, diabetes