Endotoxemia, Fasting, Immobilization, Tonic, Metabolism
Conditions
Keywords
immobilization, fasting, endotoxemia, LPS, metabolism, model of disease
Brief summary
The investigators want to establish a new model of acute febrile disease by mimicking the conditions seen in hospitalized patients in regards to inflammation, immobilisation and fasting. In this new model of disease, healthy young adults will be given lipopolysaccharide (LPS) to induce endotoxemia and inflammation/fever and then fast and bedrest for 36 hours. Glucose, fat and protein metabolism will be investigated using clamp technique and tracer methodology together with intracellular signalling pathway activation in muscle and fat biopsies. This new model of disease will later be used in another study to investigate different protein supplement´s effect on muscle waste during acute febrile disease.
Detailed description
The investigators want to establish a new model of acute febrile disease by mimicking the conditions seen in hospitalized patients in regards to inflammation, immobilisation and fasting. In this new model of disease, healthy young adults will be given lipopolysaccharide (LPS) to induce endotoxemia and inflammation on study day 1 and then fast and bedrest for 36 hours (Study day 2). Glucose, fat and protein metabolism will be investigated using clamp technique and tracer methodology together with intracellular signalling pathway activation in muscle and fat biopsies. This new model of disease will later be used in another study to investigate different protein supplement´s effect on muscle waste during acute febrile disease.
Interventions
OTHERLPS, 36 hour immobilization and fast
LPS endotoxin is administered on study day 1 and immobilization and fast continue throughout study day 1 and 2.
Sponsors
Arla
University of Aarhus
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Healthy young adults will be randomized to either intervention Endotoxemia, 36 hour immobilization and fasting or overnight fast being the control day.
Eligibility
Sex/Gender
MALE
Age
20 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Male sex * 20 \< BMI \< 30 * 20 \< Age \< 40 years * Written consent prior to trial
Exclusion criteria
* Participation in trials using ionized radiation a year prior to this trial. * Comprehensive x-ray examinations in the study period. * In case of immobilization of an extremity, the extremity should be fully re- habilitated and this should be stated by a physician or physiotherapist. The test subject's word for this will be sufficient. * Allergies to eggs or soy oil. * Diseases: Diabetes, epilepsy, ongoing infectious disease, immunodeficiency, heart disease, dysregulated hypertension.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| insulin sensitivity | After a 3 hour clamp | Measured by hyperinsulinemic euglycemic clamp technique |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ketone body metabolic changes | measured at baseline and after 3 hours of clamp | measurement of ketone bodies |
| inflammation | measurements over 36 hours | Quantified by C-reactive peptide (CRP), white blood cell count, cytokines |
| Intracellular signalling pathway activation | measured at baseline and after 3 hours of clamp | Intracellular signalling pathway activation in muscle and fat |
| Energy expenditure | measured at baseline and after 3 hours of clamp for 15 minutes | measured by indirect calorimetry |
| Glucose metabolism | measured at baseline and after 3 hours of clamp | measured by glucose tracer, calculations of rate of appearance, disappearance and endogenous glucose production |
| Protein metabolism | measured at baseline and after 3 hours of clamp | Quantified by phenylalanine and tyrosine tracer methodology (whole body and the forearm model) |
| CD163 | 0, 24 and 48 hours after LPS exposure | measures of CD163 and soluble CD163 (sCD163) after LPS exposure |
| Fat metabolism | measured at baseline and after 3 hours of clamp | measured by palmitate tracer, calculating whole body palmitate flux. Measures of free fatty acids. |
| Urea balance | measured at baseline and after 3 hours of clamp | measured by urea tracer and urine nitrogen excretion. |
| Glucose uptake by the forearm | measured at baseline and after 3 hours of clamp | Arterio-venous balance x blodflow |
| Hormonal changes | measured at baseline and after 3 hours of clamp | measures of insulin, glucagon, c-peptide and growth hormone |
Countries
Denmark
Outcome results
None listed