A model mimicking catabolic inflammatory disease; a controlled randomized study in humans

Area of Science:

• Metabolic physiology
• Human experimental models

Background:

• Inflammatory diseases are catabolic, causing insulin resistance, increased energy expenditure, lipolysis, and muscle protein loss.
• Key contributors to these metabolic changes include inflammation, malnutrition, and immobilization, common during hospitalization.
• A lack of controlled experimental models incorporating these factors hinders research into anti-catabolic interventions.

Purpose of the Study:

• To validate a human experimental model that combines systemic inflammation, fasting, and bed rest.
• To investigate the metabolic adaptations induced by this model, mimicking clinical hospitalization conditions.
• To establish a suitable platform for testing anti-catabolic interventions.

Main Methods:

• A randomized crossover design was used with six healthy young men.
• Participants underwent either overnight fasting (CTR) or a combination of systemic lipopolysaccharide exposure, 36-hour fast, and bed rest (CAT).
• Insulin sensitivity was measured using a hyperinsulinemic euglycemic glucose clamp, with tracer infusions and indirect calorimetry assessing metabolic shifts and energy expenditure.

Main Results:

• Systemic inflammation, fasting, and bed rest (CAT) significantly reduced insulin sensitivity by 41% compared to control (CTR).
• CAT increased energy expenditure by 6%, with higher lipid oxidation and lower glucose oxidation rates.
• Lipolysis markers (palmitate flux) were elevated in CAT, while C-reactive peptide levels significantly increased, confirming an inflammatory response.

Conclusions:

• The validated human experimental model effectively simulates the metabolic consequences of hospitalization, including marked insulin resistance, increased energy expenditure, and lipolysis.
• This model provides a controlled environment for studying anti-catabolic interventions in conditions mimicking clinical scenarios.
• The findings highlight the complex metabolic interplay of inflammation, fasting, and immobilization.