Effects of acute elevation of circulating fatty acids on hepatic lipid accumulation and metabolism in overweight and obese men with non-alcoholic fatty liver disease

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 22

Inclusion Criteria

Male sex
- Age 40-65 years
- Overweight/obese, BMI 25-35 kg/m2
- Healthy
- Stable dietary habits
- Must be on sulphonylurea or metformin therapy for at least 6 months with constant dose for at least 2 months, or on a dietary treatment for at least 6 months
- Well-controlled diabetes: fasting plasma glucose concentration >= 7.0 mmol/l and < 10.0 mmol/l at the time of screening.

Exclusion Criteria

Persons that have any of the following will be excluded from the study:
- Female sex
- Haemoglobin <7.8 mmol/l
- Engagement in programmed exercise > 2 hours total per week
- Liver disease, other than NAFLD
- Hypertension: blood pressure > 160 mmHg systolic or 100 mmHg diastolic
- Cardiac problems, such as angina pectoris, cardiac infarction and arrhythmias
- First degree relatives with history of liver disease and diabetes mellitus
- Alcohol consumption of more than 20 g per day (± 2 units)
- Unstable body weight (weight gain or loss > 3 kg in the past three months)
- Participation in another biomedical study within 1 month prior to the screening visit
- Insulin use
- Contraindications for MRI scan:
• Central nervous system aneurysm clips
• Implanted neural stimulator
• Implanted cardiac pacemaker of defibrillator
• Cochlear implant
• Iron- containing corpora aliena in the eye or brain
• Hearing aids and artificial (heart) valves which is contraindicated for MRS
- Subjects, who do not want to be informed about unexpected medical findings, or do not wish that their treating physician is informed, cannot participate in the study
- Liver fat content lower than 5.56%

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>- hepatic lipid content (determined non-invasively by 1H-MRS, ratio of the<br /><br>signal intensity of the CH2-lipid peak to the signal intensity of the water<br /><br>peak) before and after the high FFA condition compared to the low FFA condition<br /><br>and hepatic ATP-and Pi concentrations associated with it.<br /><br>- hepatic lipid content before exercise compared to after exercise</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- Substrate oxidation<br /><br>- Blood plasma levels of FFA, triglycerides, glucose and catecholamine<br /><br>- maximal aerobic capacity (VO2max)<br /><br>- body composition (hydrostatic weighing)</p><br>