Chylomicrons: A Key Biomarker and Risk Factor for Cardiovascular Disease and for the Understanding of Obesity

Abstract

Cardiovascular disease can be considered a condition of chronic low-grade inflammation. Postprandial hyperlipidemia and obesity can both exacerbate inflammatory processes. Postprandial lipemia stimulates the activation of leukocytes, the production of chemokines, and activation of the complement system. Obesity is also associated with postprandial hyperlipidemia by hepatic overproduction of very low-density lipoprotein (VLDL) and consequently delayed clearance of intestinally derived chylomicrons due to competition for the same metabolic pathways. Insulin resistance is one of the key elements leading to hepatic VLDL overproduction and is also a key factor in the generation of inflammation. These metabolic derangements cause accumulation of atherogenic remnant lipoproteins, which is also a proatherogenic mechanism. Change in lifestyle is the most important therapeutic strategy to stop this vicious circle of postprandial hyperlipidemia, obesity, inflammation, insulin resistance, and cardiovascular disease.

Dyslipidemia in Obesity: Mechanisms and Potential Targets

“…Small dense LDL have an increased affinity for arterial proteoglycans resulting in enhanced subendothelial lipoprotein retention [58]. However, subendothelial remnants of chylomicrons and VLDL do not need to become modified to allow uptake by scavenger receptors of macrophages in contrast to native LDL [59]. It has been described that small dense LDL are more susceptible for oxidation, in part due to less free cholesterol and anti-oxidative content [60].…”

“…Several investigators have demonstrated an association between TG-rich lipoproteins and remnant cholesterol levels with the presence of coronary [34,35,36,38,39,40,41,42,68], cerebral [37], and peripheral atherosclerosis [69]. In addition to a direct detrimental effect by chylomicron remnants on vessels [59], impaired endothelial function after an oral fat load [70] and after infusion of artificial TG-rich lipoproteins have been described [71]. This phenomenon may take place by elevated levels of FFA [72], which are generated by the action of LPL mediated lipolysis.…”

“…Lifestyle changes synergistically improve insulin resistance and dyslipidemia [59]. The amount of ingested fat and total calories are the most important dietary factors to induce obesity and its related postprandial lipemia [109].…”

Alcohol and plasma triglycerides

“…Obesity will eventually develop upon a high fat, hypercaloric diet, which contributes to the development of hypertriglyceridemia [31]. The relationship between obesity, alcohol and plasma triglycerides was confirmed in an experimental study, where participants consumed 250 ml red wine during 14 days [34 & ].…”

“…Lifestyle factors, like dietary fat consumption, body weight, smoking and physical exercise, influence plasma triglycerides as well [31,32]. Alcohol consumption can exaggerate the hypertriglyceridemia associated with an unhealthy lifestyle [7], but alcohol consumption is also related to an unhealthy diet [5].…”