Hepatic and Cardiac Metabolic Flexibility in Obese With NAFLD.

Study Overview
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Brief Summary
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Non-alcoholic fatty liver disease (NAFLD) covers a spectrum from reversible hepatic steatosis to inflammation and fibrosis termed steatohepatitis (NASH) and cirrhosis. New evidence indicates that NAFLD is associated with development of heart failure, abnormal ventricular glucose and fatty acid (FA) utilisation and cardiosteatosis. The mechanisms behind cardiac involvement and the progression from NAFLD to NASH are poorly understood but must include altered cardiac and intrahepatic lipid handling. In collaboration with renowned research groups from Oxford, Mayo Clinic and Copenhagen investigators plan comprehensive kinetic studies of heart and liver FA uptake and oxidation, ventricular function and substrate utilisation, and hepatic triglyceride (TG) secretion in order to assess mechanisms governing cardiac and hepatic lipid and glucose trafficking in subjects with NAFLD and NASH and the relationship with heart function. In addition, the investigators will assess skeletal muscle and adipose tissue enzyme activities, gene expression and protein concentrations in these subjects to define mechanisms involved in the cross-talk between heart, liver, muscle and adipose tissues. Investigators will address these questions using innovative tracer techniques (11Cpalmitate, 11C acetate, 18FDG glucose PET tracers and TG tracers) in combination with hepatic vein catherisation to study cardiac and liver substrate trafficking, as well as NMR spectroscopy, echocardiography, muscle and fat biopsies in combination with state-of-the art muscle and adipose tissue enzyme kinetics, gene- and protein expression. Effects of acute exercise will be assessed. The overarching goals are to define abnormalities and differences between NAFLD and NASH in hepatic lipid (FA and TG) metabolism and to assess the effect of exercise on both hepatic, cardiac and adipose and skeletal muscle lipid and substrate utilisation.

Official Title
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The Effect of Physical Activity on the Liver and the Heart's Metabolism of Fatty Acids in Obese With and Without NAFLD

Conditions
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NAFLD - Nonalcoholic Fatty Liver Disease

Intervention / Treatment
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* Behavioral: Exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 10 obese subject men/women with NAFLD (MR spectroskopi, fibro scanner) (BMI > 30). 10 obese subject men/women without NAFLD (MR spectroskopi, fibro scanner) (BMI > 30). age between 40-70 years Written consent before the start of the study Exclusion Criteria: known current disease Fixed Medical drug consumption, statins and antihypertensive drugs (non-beta blocker). However, pause 3 weeks before the examination date Blood donation within the last 3 months prior to the study Participation in experiments involving radioactive isotopes within the last 6 months Alcohol abuse (over 21 items per week for men and 14 for women) Smoking Weight over 130 kg Cancer patients Large intake of medication

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

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

Primary Purpose: Health Services Research
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Experimental: 1 Healthy male volunteers Behavioral: Exercise Moderate Intensity Exercise (50 % af VO2max) for 90 minutes before and after PET scanning, Experimental: 2 Healthy female volunteers Moderate Intensity Exercise (50 % af VO2max) for 90 minutes before and after a PET scanning.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy male volunteers<br>Behavioral: Exercise Moderate Intensity Exercise (50 % af VO2max) for 90 minutes before and after PET scanning. | Behavioral: Exercise<br>* Moderate Intensity Exercise (50 % af VO2max) for 90 minutes<br>|
| Experimental: Healthy female volunteers<br>Behavioral: Exercise Moderate Intensity Exercise (50 % af VO2max) for 90 minutes before and after PET scanning. | Behavioral: Exercise<br>* Moderate Intensity Exercise (50 % af VO2max) for 90 minutes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect of physical activity on the heart's metabolism of fatty acids in obese with and without NAFLD | Primary outcome: - Fatty acid uptake (mg/kg/min) in the Heart in obese with and without NAFLD | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the effect of an acute exercise bout on the improvement of cardiac FA utilization in obese with and without NAFLD. | Fatty acid oxidation (µmol/min) in the Heart in obese with and without NAFLD. | 2 years |