Accumulation of Triglyceride-Rich Lipoprotein in Subjects With Abdominal Obesity

Abstract

Abstract-The present study represents a new insight into the Biguanides and the Prevention of the Risk of Obesity (BIGPRO) 1 study population at inclusion. This population, selected basically on the basis of a high waist-to-hip ratio (Ն0.95 for men and Ն0.80 for women), is supposed to represent a group of patients with insulin resistance. The present study was undergone to establish whether apolipoprotein C-III (apoC-III) and apolipoprotein E (apoE) associated with apo B (apoC-III LpB and apoE LpB, respectively), considered to be markers of remnant accumulation, play a role in the hypertriglyceridemia associated with insulin resistance and whether they are related to other biological abnormalities frequently observed in this syndrome. In this population, the concentration of the markers of remnant accumulation increases with triglyceride levels. Therefore, correlation studies were realized to assess the relative effect of insulin and the markers of remnant accumulation on triglyceride plasma level. As a first attempt, a simple correlation analysis revealed that insulin is positively related to the markers of remnant accumulation only in hypertriglyceridemic patients (triglycerides Ն1.7 mmol/L). To assess the independent contribution of these markers, insulin, and other parameters related to the plasma triglyceride concentration, a stepwise multiple regression analysis was run. Results revealed that insulin and the markers of remnant accumulation (specifically, apoE LpB) are independent contributors to the plasma triglyceride concentration. Markers of the endothelial damage, plasminogen activator inhibitor-1, tissue plasminogen activator, and von Willebrand factor, which are often increased in the case of insulin resistance, were tested for their correlation with the markers of remnant accumulation. Plasminogen activator inhibitor-1 is positively correlated with these markers only in hypertriglyceridemic male subjects. It is concluded that increased insulin levels found in insulin resistance syndrome are associated with an increased production of triglyceride-rich lipoproteins enriched in apoC-III and apoE. The accumulation of these remnants and/or their abnormal composition in apoC-III and apoE could be an explanation for the development of hypertriglyceridemia in this syndrome. nsulin resistance syndrome includes a constellation of clinical and biological anomalies, clustering in subjects with upper body fat distribution who often exhibit insulin resistance at the cell level. 1-4 Among these anomalies are hyperinsulinemia, glucose intolerance, elevated blood pressure, impaired fibrinolytic activity, and a dyslipidemic profile characterized by a high plasma triglyceride concentration and a low HDL cholesterol level. 5,6 Triglyceride-rich lipoproteins (TGRLs) represent a mixture of particles in which apoC-III and apoE are present in multiple copies. 7 During the lipolytic process, most apoCs and apoEs are transferred to HDL. 8 -11 In addition, apoC-III inhibits lipolysis, 12-14 and apoE plays a role in the clear...

Associação entre obesidade central, triglicerídeos e hipertensão arterial em uma área rural do Brasil

“…High levels of serum TG have been observed in subjects presenting abdominal obesity 21 , and some authors have referred to the occurrence of these two factors as hypertriglyceridemic waist. There is a considerable body of evidence to indicate a strong association between hypertriglyceridemic waist and the risk of cardiovascular diseases 21,[22][23][24] .…”

Apolipoprotein C-III, metabolic syndrome, and risk of coronary artery disease

“…Increased apoB and cholesterol in circulating lipid particles is a well-known feature in CAD patients, but the notion of increased apoC-III and apoE levels in MS patients with CAD is not generally accepted. Sparse information concerning the different MS elements, such as obesity (7,8,27) or type II diabetes (28,29), exist, generally confirming the relation between hypertriglyceridemia and increase of apoC-III and apoE, but there are no specific studies reporting on MS as a unique complex. To the best of our knowledge, there are no studies evaluating the CAD risk of MS patients in relation to the extent of apoC-III increase.…”

“…In addition to the presence of hypertriglyceridemia and low serum HDL cholesterol, MS and/or insulin resistance are also characterized by an increase of small LDL particles and triglyceride (TG)-rich lipoproteins, features that also contribute to the cardiovascular disease risk (4)(5)(6)(7)(8). One of the most important and reliable markers of TGrich lipoproteins levels is apolipoprotein C-III (apoC-III).…”

“…(11)]. In spite of this important role of apoC-III in TG metabolism, relatively few data exist in the literature regarding the relationships between apoC-III and hypertriglyceridemia in MS patients (6)(7)(8). The atherogenetic role of apoC-III (12)(13)(14)(15)(16)(17), as well as that of hypertriglyceridemia in MS for coronary artery disease (CAD) risk (3)(4)(5)(6), is well recognized.…”

PPARα mediates the hypolipidemic action of fibrates by antagonizing FoxO1

“…Due to its proatherogenic profile, hypertriglyceridemia is a major contributing factor for the pathogenesis of atherosclerosis and coronary artery disease in obesity and type 2 diabetes. While the pathophysiology of hypertriglyceridemia is poorly understood, its close association with visceral adiposity and type 2 diabetes implicates insulin resistance as a causative factor in the development of hypertriglyceridemia (5,12,22,29,42). However, the molecular events that link insulin resistance to the pathogenesis of hypertriglyceridemia remain elusive.…”