Diabetes, Obesity
Conditions
Keywords
VLDL-TG, Metabolism, Exercise, Free Fatty Acids
Brief summary
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
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.
Interventions
DRUGAcipimox
Tablet Acipimox 250 mg administered 4 times previous to and during the investigation day
Sponsors
University of Aarhus
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effects of exercise and antilipolysis on FFA and VLDL-TG kinetics | 6 hour investigation day | 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. |
Countries
Denmark
Outcome results
None listed