Effects of acute elevation of circulating fatty acids on skeletal muscle lipid accumulation in healthy lean young men

There is increasing evidence that skeletal muscle lipid content
(IntraMyoCellular Lipid, IMCL) markedly increases the risk of metabolic
complications, including insulin resistance and cardiovascular events. We
hypothesize that skeletal muscle is passively taking up FFAs when the
availability is high, thereby leading to an increased storage. To test this
hypothesis, we want to manipulate FFA levels, by means of exercise, and monitor
intramuscular lipid content.
Objective: To examine the effect of an exercise-induced elevation of FFA on
skeletal muscle lipid content. To this end, we compare skeletal muscle lipid
content at baseline and after an exercise protocol and again after a four-hour
recovery period from exercise, once in a condition with high FFA concentration,
once with low FFA concentration. To achieve high- versus low FFA
concentrations, we chose a protocol with cycling exercise either with- or
without glucose supplementation.
Study design: Skeletal muscle lipid content will be determined in a condition
with high plasma FFA (cycling and recovery in fasted state) and in a low FFA
condition (cycling and recovery with glucose supplementation). Remaining fasted
during cycling and recovery has been shown to result in strongly increased FFA
levels, while glucose supplementation completely blunts the increase in FFA. To
determine the effect of acute exercise, skeletal muscle lipid content will be
measured before and after cycling.
Study population: In this study 20 healthy lean young men (18-30 years, BMI
18-25 kg/m2) will be recruited.
Intervention (if applicable): Subjects will perform a two-hour cycling test,
once fasted (high FFA condition) and once with glucose supplementation (low FFA
condition). To determine the effect of high versus low FFA concentration,
skeletal muscle lipid content will be determined in both conditions at baseline
and 4 hours after recovery from exercise. To determine the effect of acute
exercise, skeletal muscle lipid content will be compared before and after the
cycling exercise.
Main study parameters/endpoints: Skeletal muscle lipid content before, directly
after exercise and 4 h post exercise (determined from muscle biopsies) with or
without glucose supplementation.
Nature and extent of the burden and risks associated with participation,
benefit and group relatedness: Subjects will come to the university three
times. First the subjects will be screened to access eligibility, which will
include filling in a medical history questionnaire, and a measurement of height
and body weight. Body composition will also be accurately determined by
hydrostatic weighing and the subjects* maximal aerobic capacity will be
determined by an exercise test. In total this will take approximately 2 hours.
The second and the third visit are test days (ca. 8 h), for which subjects have
to report to the university in the morning in the fasted state. During these
test days subjects will undergo three muscle biopsies (before, directly after
exercise and again 4 h post exercise) and exercise for a total duration of 2
hours.
No direct health benefit for the participants is expected. The experimental
procedures are without risks, except for blood sampling and sampling of muscle
biopsies, which can occasionally cause a local haematoma or bruise and the
maximal test and cycling protocol can cause muscle soreness. Measurements
performed during the time course of the study can potentially lead to
coincidental medical findings. Subjects will be informed about such a finding
and possible advised to contact a doctor about this.

To examine the effect of an exercise-induced elevation of FFA on skeletal
muscle lipid content. To this end, we compare skeletal muscle lipid content at
baseline and after an exercise protocol and again after a four-hour recovery
period from exercise, once in a condition with high FFA concentration, once
with low FFA concentration. To achieve high- versus low FFA concentrations, we
chose a protocol with cycling exercise either with- or without glucose
supplementation.

Skeletal muscle lipid content will be determined in a condition with high
plasma FFA (cycling and recovery in fasted state) and in a low FFA condition
(cycling and recovery with glucose supplementation). Remaining fasted during
cycling and recovery has been shown to result in strongly increased FFA levels,
while glucose supplementation completely blunts the increase in FFA. To
determine the effect of acute exercise, skeletal muscle lipid content will be
measured before and after cycling.

Subjects will perform a two-hour cycling test, once fasted (high FFA condition)
and once with glucose supplementation (low FFA condition). To determine the
effect of high versus low FFA concentration, skeletal muscle lipid content will
be determined in both conditions at baseline and 4 hours after recovery from
exercise. To determine the effect of acute exercise, skeletal muscle lipid
content will be compared before and after the cycling exercise.

Subjects will come to the university three times. During the first visit
subjects height and body weight will be measured. Body composition will also be
accurately determined by hydrostatic weighing and the subjects* maximal aerobic
capacity will be determined by an exercise test. In total this will take
approximately 2 hours.
The second and the third visit are test days (ca. 8 h), for which subjects have
to report to the university in the morning in the fasted state. During these
test days subjects will undergo three muscle biopsies (before, directly after
exercise and again 4 h post exercise) and exercise for a total duration of 2
hours.
No direct health benefit for the participants is expected. The experimental
procedures are without risks, except for blood sampling and sampling of muscle
biopsies, which can occasionally cause a local haematoma or bruise and the
maximal test and cycling protocol can cause muscle soreness. Measurements
performed during the time course of the study can potentially lead to
coincidental medical findings. Subjects will be informed about such a finding
and possible advised to contact a doctor about this.