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.