Effects of acute elevation of plasma free fatty acids on cardiac lipid accumulation in healthy lean young men

There is increasing evidence that Cardiac lipid content (IntraCardiomyoCellular
Lipid, ICCL), is involved in the etiology of dilated cardiomyopathy and heart
failure4,5. We hypothesize that the heart 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 and monitor cardiac lipid content
and cardiac function and energy status.
Recently, proton magnetic resonance spectroscopy has been adapted to enable
quantification of lipid content in cardiac muscle16,17.

The major research objective is:
- to examine whether elevation of plasma FFAs results in cardiac lipid
accumulation and whether this influences cardiac function negatively.
Additional research objective:
- to examine whether cardiac lipid content is decreased after cycling (as it is
the case in skeletal muscle).

Cardiac lipid content and cardiac function 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.

Subjects will perform a two-hour cycling test, once fasted (high FFA condition)
and once with glucose supplementation (low FFA condition). Before and after the
cycling test and again after a three-hour recovery period, cardiac lipid,
cardiac function and energy status will be performed by MRI/MRS.

First visit: determination of maximal aerobic capacity and body composition (ca
1.5 hours). Second and third visit (test days, ca. 8h): After a baseline
MRI/MRS-scan, subjects will cycle for two hours, immediately after cycling
another MRI/MRS-scan will be performed and after two more hours of recovery
another MRI/MRS-scan will be perfored. During cycling and recovery period,
indirect calorimetry will be performed and blood will be sampled repeatedly (10
ml) from a cathetherplaced in the anticubital vein. On one visit, subjects will
get a glucose drink, on the other occasion only water. The experimental
procedures are without risks, except for insertion of a cathether for blood
sampling, which can occasionally cause a local haematoma or bruise to occur.
MRS is a safe procedure (no ionizing radiation), with no known health risk as
long as none of the exclusion criteria is met.