CIRcadian Rhythms and CortisoL. Effects on Substrate Metabolism and Clock Gene Expression and Functioning

CIRcadian Rhythms and CortisoL. Effects on Substrate Metabolism and Clock Gene Expression and Functioning

The aim of this project is to study the effects of exogenous glucocorticoid exposure on substrate metabolism, energy expenditure and correlates of circadian rhythmicity in healthy adults. The hypotheses are:

Short-term high dose glucocorticoid exposure in healthy subjects disrupts:

• The inherent circadian pattern of the respiratory exchange ratio and REE
• Sleep quality, appetite and food intake
• Clock gene expression and function in adipose tissue, skeletal muscle and blood leukocytes

Inclusion Criteria:

• Male sex
• BMI 20-30 kg/m2
• Written informed consent

Exclusion Criteria:

• Any chronic disease requiring daily medication excluding atopic skin or hay fever
• Alcohol consumption >21 units per week
• Strong CYP3A4 inhibitors or inducers
• Use of glucocorticoid (GC) formulations: Inhaled corticosteroids, intra-articular or intramuscular injections, steroid creams European steroid group IV-V used in the genital area
• Permitted glucocorticoid formulations: eye-drops, nasal spray, GC creams European steroid group I-III, and European steroid group IV-V used in the non-genital area only
• Shift work
• Severe claustrophobia
• Use of melatonin
• Previous diagnosis of a sleep disorder
• Known severe sleep apnea (>30 respiration breaks/hour over 10 seconds)
• Deemed unable to complete the study safely by investigator