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This study will investigate free fatty acid and VLDL-TG metabolism before and during exercise with and without pharmacological antilipolysis by the niacin antagonist Acipimox. Main focuses will be VLDL-TG and free fatty acid metabolism as well as expression of membrane proteins in fat- and muscle biopsies.
Insulin resistance in liver and skeletal muscle is of central pathogenic significance in the development of type 2 diabetes. The molecular connections are unresolved but high levels of free fatty acids and triglyceride is probably involved. Diabetic subjects and to a lesser extent obese subjects have increased triglyceride levels, this could be due to an abnormal turnover of VLDL-TG. It is not yet investigated whether VLDL-TG kinetics changes during pharmacological antilipolysis. Using the aseptic ex-vivo labeling technique (developed in our laboratories) we will investigate this issue in sedentary healthy men. After a 3 hour basal period subjects will exercise on a bike for 60 minutes at 60% of VO2max. In both basal and exercise period one muscle and one fat biopsy will be obtained, further blood samples will be drawn to examine FFA and VLDL-TG metabolism etc..
This new knowledge will contribute to the understanding of metabolic disorders like type 2 diabetes and obesity.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Acipimox | Experimental | Tablet Acipimox 250 mg administered 4 times previous to and during the investigation day |
|
| Placebo | No Intervention | Placebo tablets will be administered 4 times previous to and during the investigation day |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Acipimox | Drug | Tablet Acipimox 250 mg administered 4 times previous to and during the investigation day |
|
| Measure | Description | Time Frame |
|---|---|---|
| Effects of exercise and antilipolysis on FFA and VLDL-TG kinetics | Healthy untrained men, investigated with pharmacological antilipolysis by Acipimox (Olbetam) and placebo on 2 occasions. Each day consists of 3 hour basal period and 90 minutes exercise on a bicycle at 60% of VO2-maximum. During the day glucose and lipid metabolism is investigated by glucose and VLDL tracer, as well as indirect calorimetrics. Cellular signaling is investigated by 2 muscle- and 2 fat biopsies each day. | 6 hour investigation day |
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Inclusion Criteria:
- healthy, untrained males
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Soren Nielsen, Dr. med. | University Hospital of Aarhus | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital of Aarhus, Norrebrogade | Aarhus | Aarhus | 8000 | Denmark | ||
| University Hospital of Aarhus, Norrebrogade |
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| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D009765 | Obesity |
| D009043 | Motor Activity |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| C027696 | acipimox |
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| Aarhus |
| Aarhus |
| 8 |
| Denmark |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001519 | Behavior |