Endocrine Regulation of Lipolysis in Obesity and Diabetes

Study Overview
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Brief Summary
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Adipose tissue (AT) dysfunction is a commonly observed feature of metabolic dysfunction in obesity and diabetes. An important characteristic when examining AT function is the capacity to break down stored lipids (i.e. lipolysis) and its regulation. In the present study, the aim was to investigate whether atrial natriuretic peptide-mediated lipolysis is altered in different adipose tissue depots (subcutaneous and visceral adipose tissue) of obese subjects with or without type 2 diabetes, compared to age-matched lean men. Eventually, the knowledge gained from this research will contribute to a better understanding of the present adipose tissue dysfunction and to the optimization of exercise programs for people with obesity and diabetes.

Official Title
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Atrial Natriuretic Peptide (ANP)-Induced Lipid Mobilization Regulation in Different Adipose Tissue Depots of Obese Subjects

Conditions
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Obesity, Diabetes

Intervention / Treatment
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* Other: adipose tissue sampling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Lean group: BMI < 25 kg/m², insulin sensitive (HOMA-Insuline Resistance (IR) < 2.3), age 40-65 Obese groups: BMI > 30 kg/m², presence or absence of type 2 diabetes based on use of glucose lowering medication or HbA1c > 6.5%, age 40-65 Exclusion Criteria: presence of a history of heart, lung or kidney disease and/or presence of endocrine anomalies. Use of beta-blockade medication.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 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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Design Details

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: lean men<br> | Other: adipose tissue sampling<br>* adipose tissue (subcutaneous and visceral adipose tissue) sampling during abdominal surgery and phenotype determination<br>|
| Other: Obese men without type 2 diabetes<br> | Other: adipose tissue sampling<br>* adipose tissue (subcutaneous and visceral adipose tissue) sampling during abdominal surgery and phenotype determination<br>|
| Other: Obese men with type 2 diabetes<br> | Other: adipose tissue sampling<br>* adipose tissue (subcutaneous and visceral adipose tissue) sampling during abdominal surgery and phenotype determination<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycerol release by mature adipocytes, isolated from subcutaneous and visceral adipose tissue, upon stimulation with isoprenalin or ANP (ex vivo) | Investigation of concentration effect of ISO/ANP on lipolysis (glycerol release) by mature adipocytes isolated from adipose tissue biopsies, glycerol release is measured in the incubation medium following a 3 hour incubation period. Measured for adipose tissue (subcutaneous and visceral adipose tissue) of both lean and obese subjects | day 1 | 
| ANP receptor expression profiles on mRNA and protein level in both adipose tissue depots for both lean and obese subjects. | Receptor expression determination in order to clarify the underlying mechanism responsible for possible differences in lipolytic responses. | day 1 | 
| Adipose tissue inflammation | Adipose tissue inflammation (by means of FACS analysis) and its relation to insulin sensitivity and adipose tissue function in lean, obese and obese diabetics subjects. | day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body composition | Body composition (body fath percentage), measured by BIA | day 1 | 
| BMI (kg/m²) |  | day 1 | 
| body height (m) |  | day 1 | 
| weight (kg) |  | day 1 | 
| hip circumference (cm) |  | Day 1 | 
| waist (cm) |  | Day 1 | 
| blood glucose |  | day 1 | 
| blood insuline |  | day 1 | 
| blood FFA |  | day 1 | 
| blood triglycerides |  | day 1 | 
| blood glycated hemoglobin |  | day 1 | 
| blood ANP | fasting blood sample to determine blood glucose, insulin, FFA, , glycated hemoglobin and ANP | day 1 | 
| blood pressure (mmHg) |  | Day 1 | 
| Concomitant medication |  | Day 1 |