Leucine, mTOR and Athero

Study Overview
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Brief Summary
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High protein low carbohydrate diets have become popular in recent years to help facilitate weight loss. It is controversial if these diets are associated with an increased risk of cardiovascular disease. Recent work in mice has implicated monocytes/macrophages and mTOR signaling as the culprit cell type driving the increased cardiovascular risk with high protein diets. We aim to build on this preclinical research by evaluating the effects of liquid meals with different protein and leucine (a potent mTOR activator) contents on circulating human monocytes and platelets. Study participants will be given either a low protein liquid meal, a high protein liquid meal, or a low protein liquid meal with additional leucine. Blood will be collected from study participants just just prior to and for several hours after ingestion of the meals. Activation of amino acid-dependent signaling pathways (particularly mTOR) and downstream sequelae will be evaluated in the isolated monocytes and platelets.

Official Title
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Protein, Platelet, and Monocyte

Conditions
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Atherosclerosis

Intervention / Treatment
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* Other: Meal


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years or older able to drink milk-based liquid mixed meal Exclusion Criteria: Current Pregnancy Allergies to meal ingredients History of Diabetes History of Heart Disease History of High blood pressure History of Stroke History of Cancer History of Organ transplant Taking Rapamycin/Sirolimus Taking Torisel/Temsirolimus Taking Afinitor/Everolimus Taking any statin medication

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 95 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
Interventional Model Description: Single-group crossover
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard protein meal<br>Participants will receive a standard protein meal, containing about 10% of energy as protein | Other: Meal<br>* Liquid mixed meal with different amounts of protein and leucine<br>|
| Active Comparator: High protein meal<br>Participants will receive a high protein meal, containing about 50% of energy as protein | Other: Meal<br>* Liquid mixed meal with different amounts of protein and leucine<br>|
| Active Comparator: Low protein meal + leucine<br>Participants will receive a standard protein meal, containing about 10% of energy as protein to which leucine has been added to match the total leucine content of the high protein meal | Other: Meal<br>* Liquid mixed meal with different amounts of protein and leucine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| p-mTOR in monocytes |  | change from before meal at 1 hour and 3 hours, compared to before |