INTRODUCTION
The blood lipid imbalance common in individuals with the Met Synd (i.e.,
high TG, LDL-c, VLDL-c and low HDL-c) is strongly correlated with the
risk of atherogenesis and endothelial disfunction by stimulation of
thrombogenic and inflammatory pathways
[1]. LDL-C has been
regarded as the main lipoprotein inducing the accumulation of sterols in
macrophages while chylomicrons are not considered to be directly
involved in atherogenesis, because of their larger size and inability to
efficiently penetrate arterial tissue. However, once chylomicrons are
hydrolyzed their remnant penetrates arterial tissue and becomes
preferentially trapped within the subendothelial space
[2]. Thus, the risk for atherogenic
plaque formation and endothelial dysfunction increases after ingestion
of meals with high fat content [3] due
to the rise in lipoproteins remnant (i.e., chylomicrons and VLDL with
high cholesterol content).
At rest, hypercholesteremic Met Synd individuals have an exaggerated
postprandrial triglyceride (PPTG) response compared to lean counterparts
for the same meal ingestion [4]. This
seems to be due to increased blood TG influx from the ingested fat
(chylomicrons) [4] although increases
in hepatic secreted triglycerides (VLDL-TG) could also be involved. A
bout of exercise could activate endothelial LPL and therefore lipolysis
to reduce PPTG. However, it is unclear if exercise lowering PPTG,
reflects only an increased clearance of TG (i.e., by muscles, adipocytes
or liver) or also reduced intestinal lipoprotein formation
[5]. Each lipoprotein is surrounded by
a single copy of apolipoprotein, being the B type the most
representative of LDL particle concentration. A subtype of this, Apo
B48, is the major apolipoprotein involved in the formation of
chylomicrons. Enzyme-linked immunosorbent assay (ELISA) permits to
measure blood concentration of apolipoprotein B48 and B100 to
investigate the intestinal vs the hepatic origin of postprandial
lipoproteins. This could be used to unveil what is the mechanism behind
the reductions in PPTG with exercise or statin treatment.
Statins (3-hydroxy-methyl-glutaryl coenzyme A reductase inhibitors) are
the main pharmacological treatment for hypercholesterolemia. Statins
effectively inhibit liver cholesterol synthesis inducing the expression
of hepatic LDL-receptors in hepatocyte cell surface
[6] which in turn catabolizes Apo B
containing lipoproteins (i.e., chylomicrons, VLDL-c, LDL-c and IDL-c).
Statin effects on reducing blood fasting TG extends to the PPTG
[7, 8].
The effects of statin on reducing PPTG may not just involve enhancing
liver TG clearance, but also clearance by other tissues. In
normolipidemic subjects statins lowers VDLD-c pool which triggers a
reduction of Apo C-III, a protein that inhibits LPL
[8, 9].
The coordinated actions of exercise (non-pharmacological) and statin
(pharmacological) therapies to reduce PPTG are starting to be explored
[7].
This study investigates the effects of 3HMGCoA reductase inhibitor
(statins) on postprandial intestinally and hepatically derived
lipoproteins (Apo B48 and 100, respectively) in Met Synd
hypercholesteraemic individuals. Since Met Synd individuals are more
susceptible to developing cardiovascular disease, correcting PPTG with
bouts of exercise prior to the ingestion of a high-fat meal could became
a therapeutic measure of clinical importance in this population. The
present study investigates the effect of a bout of exercise before a
high-fat meal on lowering PPTG, blood lipoproteins and its possible
interactions with statin medication. Finally, all data is compared to a
sample of metabolically healthy individuals to assess treatment capacity
to revert blood lipids to normal values. Our hypothesis was that the
combination of exercise and statin could normalize PPTG in Met Synd
hypercholesteremic individuals.