Effects of Free Fatty Acids and 3-hydroxybutyrate on Protein, Glucose, Lipid Metabolism and Intracellular Signals.

Study Overview
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Brief Summary
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The investigators hypothesize that the investigators can detect protein-sparing effects of administration of the ketone 3-hydroxybutyrate and free fatty acids during simulation of an acute inflammatory disease. The investigators use the infusion of endotoxin, US standard reference E.coli in healthy subjects as a model for inflammation / infection and to evaluate the effect on protein metabolism using different tracers and the investigators can measure the various intracellular signaling pathways of selected muscle and adipose tissue.

Official Title
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Effects of Free Fatty Acids and 3-hydroxybutyrate on Protein, Glucose, Lipid Metabolism and Intracellular Signals; a Study on Muscle Wasting and Metabolism During Acute Inflammation and Potential Anabolic Mechanisms.

Conditions
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Systemic Inflammatory Response Syndrome

Intervention / Treatment
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* Other: Endotoxin, US standard reference E.coli


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 20 < body mass index < 30 kg/m2. written and orally informed consent before enrollment. Exclusion Criteria: participation in other studies using radioactive tracers or other exposure to radiation (X-rays, scintigraphy etc). allergy to soy products or eggs diabetes, any type epilepsy ongoing infection immune deficiency cardiovascular disease dysregulated hypertension primary muscles disease, congenital or acquired

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo (isotonic saline)<br>Endotoxin + isotonic saline. Reference for model of acute inflammatory illness | Other: Endotoxin, US standard reference E.coli<br> <br> |
| Experimental: Acipimox + Placebo (isotonic saline)<br>Endotoxin + Acipimox + Placebo (isotonic saline). Intervention: blockage of endogenous lipolysis. | Other: Endotoxin, US standard reference E.coli<br> <br> |
| Experimental: Acipimox + free fatty acids<br>Endotoxin + Acipimox + free fatty acids. Intervention: free fatty acids | Other: Endotoxin, US standard reference E.coli<br> <br> |
| Experimental: Acipimox + 3-hydroxybutyrate<br>Endotoxin + Acipimox + 3-hydroxybutyrate. Intervention: 3-hydroxybutyrate | Other: Endotoxin, US standard reference E.coli<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Protein metabolism | Measurements of protein oxidation during intervention using radioactive tracer techniques. | 6 hours intervention period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Activated intracellular signalling pathways | Measurements on biopsies from muscle and fatty tissue taken on day of study | study day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sepsis, cytokine release, fever