The Role of Atrial Natriuretic Peptide in the Lipolytic Process: Effect of Obesity and Exercise

Study Overview
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Brief Summary
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In the developing countries, obesity prevalence is on a dramatic rise. Obesity is related to co-morbidities and as a result, obesity significantly shortens life expectancy and lowers quality of life. To prevent this, participation in exercise or training programs is absolutely necessary, in order to generate adipose tissue mass loss. The amount of adipose tissue mass loss is, amongst others, dependent on lipolysis which is under endocrine regulation by, mainly, catecholamines, insulin and atrial natriuretic peptide. However, large variations in adipose tissue mass loss and gain are likely in obese subjects, possibly due to a decreased lipolytic effect of these hormones (as was shown for catecholamines in the subcutaneous adipose tissue of obese subjects). However, the relative contribution of atrial natriuretic peptide in the lipolytic process remains elusive, particularly in subjects with obesity, which show an increased plasma expression of atrial natriuretic peptide. The aim of the present study is to observe the contribution of atrial natriuretic peptide in the subcutaneous adipose tissue of obese subjects. This will be tested by measurements of extracellular glycerol levels (by microdialysis) in the subcutaneous adipose tissue in situ at rest and during endurance exercise under local beta- and alpha-blockade. Eventually, the knowledge gained from this research will contribute to the optimization of exercise programs for people with obesity.

Official Title
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The Contribution of Atrial Natriuretic Peptide in Lipid Mobilization of Subjects With Obesity, Both During Rest and Exercise

Conditions
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Obesity

Intervention / Treatment
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* Other: subcutaneous adipose tissue microdialysis under local beta/alpha blockade


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Obese group: BMI > 30 kg/m², sedentary (no regular physical activity last 6 months), insulin sensitive or insulin resistant Lean controls: BMI > 18.5 kg/m² and < 25 kg/m², regular physical activity, insulin sensitive Exclusion Criteria: Regular glucose lowering medication or beta blockade medication Presence of chronical diseases Orthopedic or neurological problems

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 60 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 |
| --- | --- |
| persons with obesity<br> | Other: subcutaneous adipose tissue microdialysis under local beta/alpha blockade<br>* adipose tissue lipolysis under local beta/alpha blockade in abdominal subcutaneous adipose tissue, using microdialysis<br>|
| lean persons<br> | Other: subcutaneous adipose tissue microdialysis under local beta/alpha blockade<br>* adipose tissue lipolysis under local beta/alpha blockade in abdominal subcutaneous adipose tissue, using microdialysis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subcutaneous adipose tissue microdialysis | abdominal subcutaneous adipose tissue microdialysis during rest and exercise; basal + under local alpha- and beta-blockade. | week 1 | 
| Atrial natriuretic peptide (ANP) Response | measurement systemic ANP response (venous blood sampling) | week 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Central insulin sensitivity | Fasting serum insulin, homeostasis model assessment insulin resistance and measures of central insulin sensitivity derived from an oral glucose tolerance test (75g) | screening | 
| Echocardiography | heart function by means of standard echocardiography | Day 1 | 
| Maximal oxygen uptake (ml/O2/kg/min) | measured using indirect calorimetry and an incremental bicycle protocol | Day 1 | 
| Anthropometry | body composition, measured using dual x-ray absorptiometry, height, weight, waist and hip circumference | screening | 
| Abdominal subcutaneous adipose tissue biopsy | biochemical, proteomics and morphological analyses | week 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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obesity, adipose tissue lipolysis, lipolysis, microdialysis, atrial natriuretic peptide