Acylcarnitines and Insulin Resistance

The Western lifestyle and prevalent obesity are the main causes of the strongly
increasing incidence of type 2 Diabetes Mellitus, a condition characterized
mainly by decreased insulin sensitivity of liver and skeletal muscle. It is
suggested that insulin sensitivity is caused by incomplete fatty acid oxidation
(FAO) due to high lipid burden in obese humans. The increased lipid level
enhances beta-oxidation, but is not accurately followed by tricarboxylic acid
(TCA) cycle and electron transport chain (ETC) velocity. In order to be
oxidized, fatty acids need carnitine to pass the mitochondrial membrane.
Together they form acylcarnitine, which is transported by the membrane
transporter CACT from cytosol into the mitochondrium.
Several relations between insulin resistance and acylcarnitines are studied and
described, as acylcarnitines correlate negatively with insulin sensitivity. In
obese insulin resistant subjects the activity of CPT1 and CACT are decreased,
resulting in decreased carnitine transport over the mitochondrial membrane.
Additionally, an accumulation of long chain ACs is found in obese insulin
resistant subjects. We hypothesize that long chain ACs might be a keyplayer in
the induction of insulin resistance.

Primary: To investigate plasma AC profiles of lean and obese subjects in
relation to body composition, BMI, insulin sensitivity and energy expenditure.
Secondary: To determine if plasma ACs reflect adipose (subcutaneous/visceral)
tissue, liver or muscle ACs.

Subjects who will undergo elective abdominal surgery will be recruited on the
surgical outpatient clinic. All subjects will undergo a short physical
examination and laboratory investigation.

Prior to surgery the patients will be characterized metabolically and insulin
sensitivity will be determined. These data will be correlated with
acylcarnitine profiles in plasma, muscle, liver and adipose tissue from
biopsies taken during surgery.
There is no study intervention: patients are studied once.

- Prior to surgery a full medical history, physical examination, blood
withdrawal, a 7 point Oral Glucose Tolerance Test and Resting Energy
Expenditure test will take place. There are no risks to these actions.
- During surgery biopsies will be taken from abdominal muscle, abdominal fat,
liver tissue and optionally femoral muscle tissue. These biopsies can
potentially cause haematomas, which will be managed by the surgeon during
surgery.
- Subjects will experience no benefits from this study.