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

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.

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