Study of the Effects of Overfeeding on Glucocorticoids in Lean and Obese Subjects

Study Overview
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Brief Summary
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Investigators suggest that in lean subjects cortisol increases in response to overfeeding and that this increase is blunted in obese subjects. A group of 18 male healthy lean subjects and another group of 18 male healthy obese subjects will undergo a high-calorie meal test. Prior to the meal intake, an indirect calorimetry, bioelectrical impedance, heart rate variability, a fasting blood sample and a perceived stress questionnaire will be assessed. After intake of the study meal, blood tests will be performed in order to measure the secretion of cortisol, glucose and lipid metabolism and inflammatory markers. Indirect calorimetry will be assessed again 60 and 180 minutes after the meal intake.

Detailed Description
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Obesity is one of the most serious health problems in the 21st century. High energy food and a sedentary lifestyle are driving the current obesity pandemic. These factors activate the hypothalamic-pituitary-adrenal (HPA) axis, the key regulatory pathway of energy homeostasis. Activation of the HPA-axis leads to secretion of glucocorticoids from the adrenal glands, which control energy homeostasis by mobilizing and redistributing energy substrates. Animal models of obesity have shown that glucocorticoids play a key role in the development of the metabolic syndrome. However, studies in humans yielded conflicting results. These studies have a major limitation in common. They do not consider glucocorticoid rhythmicity but rather investigate a snapshot of glucocorticoid secretion. Rhythmicity, however, is crucial because already minor glucocorticoid phase disturbances cause disease and could contribute to obesity. Interestingly, excessive food intake may increase cortisol levels in healthy subjects . The consequence of this food-induced cortisol peak is not understood, but it may be key to restoring energy homeostasis after a meal. Whether the food-induced cortisol peak in obese subjects is disturbed is not known With this study, investigators aim to better understand the role played by glucocorticoids in the origin of overweight and obesity. Researchers will investigate, in lean and obese subjects, whether the pulsatile release of cortisol increases after intake of a high-calorie meal. 36 subjects will take part in the study: a group of 18 male lean subjects and a second group of 18 male obese patients.

Official Title
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The Acute Response of Glucocorticoids Upon Food Intake

Conditions
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Overweight and Obesity

Intervention / Treatment
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* Other: High-calorie meal


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index (BMI) >18,5 and <25 kg/m2 BMI >30 kg/m2 Exclusion Criteria: Any clinically significant concomitant diseases in lean subjects Any clinically significant concomitant diseases in obese subjects apart from features of the metabolic syndrome (dyslipidemia, arterial hypertension and insulin resistance) Lactose intolerance Severe food allergy Regular alcohol consumption (>30 g/d) Regular fitness training (>4 hours/week) Previous enrolment in a clinical trial within the last 3 months Inability or contradictions to undergo the investigated intervention Inability to follow the procedures of the study

Ages Eligible for Study
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Minimum Age: 18 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Lean subjects<br>24 hours before the study visit, participants will be asked to refrain from alcohol and strenuous exercise. Patients will be asked to remain fasted 10 hours before the study visit takes place. On the day of the study visit, patients will be admitted to the hospital and, after intake of the study meal, blood samples will be taken. | Other: High-calorie meal<br>* Intake of a high-calorie meal (2500-3000 calories) within 15 minutes.<br>|
| Obese subjects<br>24 hours before the study visit, participants will be asked to refrain from alcohol and strenuous exercise. Patients will be asked to remain fasted 10 hours before the study visit takes place. On the day of the study visit, patients will be admitted to the hospital and, after intake of the study meal, blood samples will be taken. | Other: High-calorie meal<br>* Intake of a high-calorie meal (2500-3000 calories) within 15 minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pulsatile secretion of cortisol in response to a high-calorie meal (nmol/l) | Blood test | 195 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Thyroid hormones (nmol/l) | Blood test | 195 minutes | 
| Growth Hormone (mIU/l) | Blood test | 195 minutes | 
| Catecholamines (pg/ml) | Blood test | 195 minutes | 
| Adrenocorticotropic Hormone (ACTH) (pg/ml) | Blood test | 195 minutes | 
| Glucagon-like-peptide-1 (GLP-1) (pg/ml) | Blood test | 195 minutes | 
| Gastric inhibitory polypeptide (GIP) (pg/ml) | Blood test | 195 minutes | 
| Peptide YY (PYY) (pg/ml) | Blood test | 195 minutes | 
| Glucose (mmol/l) | Blood test | 195 minutes | 
| Insulin (mIU/l) | Blood test | 195 minutes | 
| C-Peptide (pmol/l) | Blood test | 195 minutes | 
| Total cholesterol (mmol/l) | Blood test | 195 minutes | 
| Low density lipoprotein (LDL)-cholesterol (mmol/l) | Blood test | 195 minutes | 
| High density lipoprotein (HDL)-cholesterol (mmol/l) | Blood test | 195 minutes | 
| Triglycerides (mmol/l) | Blood test | 195 minutes | 
| Growth differentiation factor 15 (GDF15) (ng/l) | Blood test | 195 minutes | 
| High-sensitive c-reactive Protein (hsCRP) (mg/l) | Blood test | 195 minutes | 
| Interleukin-6 (IL-6) (pg/ml) | Blood test | 195 minutes | 
| Interleukin-8 (IL-8) (pg/ml) | Blood test | 195 minutes | 
| Interleukin-1 receptor Antagonist (IL-1Ra) (pg/ml) | Blood test | 195 minutes | 
| Heart rate (bpm) | Heart rate variability analysis | 5 minutes | 
| Blood pressure: diastolic and systolic blood pressure (mmHg) | Standard blood pressure monitor | 1 minute | 
| Weight: kilogram body weight (kg) | Standard scale | 1 minute | 
| Energy expenditure: basal metabolic rate | Indirect calorimetry | 200 minutes | 
| Substrate utilisation: respiratory quotient | Indirect calorimetry | 200 minutes | 
| Fat and lean mass (kg) | Body impedance analysis | 20 minutes | 
| Total body water (l) | Body impedance analysis | 20 minutes | 
| Appetite: visual analogue scale rating | Visual analogue scale | 3 hours | 
| Stress: perceived stress Levels (0-56) | Perceived stress questionnaire | 5 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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obesity, overweight, cortisol, overfeeding, glucocorticoids