Effect of Pharmacological Anti-lipolysis on FFA and VLDL-TG Metabolism Before and During Exercise

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Effect of Pharmacological Anti-lipolysis on FFA and VLDL-TG Metabolism Before and During Exercise

Conditions
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Diabetes, Obesity

Intervention / Treatment
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* Drug: Acipimox


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - healthy, untrained males Exclusion Criteria: medication history of malignancy, alcohol abuse or drug abuse participation in isotope trials in the last 6 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acipimox<br>Tablet Acipimox 250 mg administered 4 times previous to and during the investigation day | Drug: Acipimox<br>* Tablet Acipimox 250 mg administered 4 times previous to and during the investigation day<br>|
| No Intervention: Placebo<br>Placebo tablets will be administered 4 times previous to and during the investigation day | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VLDL-TG, Metabolism, Exercise, Free Fatty Acids