Alteration in lipoprotein lipase activity bound to triglyceride-rich lipoproteins in the postprandial state in type 2 diabetes

Abstract

Postprandial lipid metabolism is largely dependent upon lipoprotein lipase (LPL), which hydrolyses triglycerides (TGs). The time course of LPL activity in the postprandial state following a single meal has never been studied, because its determination required heparin injection. Recently, we have shown that LPL activity could be accurately measured in nonheparinized VLDL using a new assay aiming to determine the LPL-dependent VLDL-TG hydrolysis. Based on the same principle, we used in this study TG-rich lipoprotein (TRL)-bound LPL-dependent TRL-TG hydrolysis (LTTH) to compare the time course of LPL activity of 10 type 2 diabetics to that of 10 controls, following the ingestion of a lipid-rich meal. The peak TG concentration, reached after 4 h, was 67% higher in diabetics than in controls ( P Ͻ 0.005). Fasting LTTHs were 91.3 ؎ 15.6 in controls versus 70.1 ؎ 4.8 nmol NEFA/ml/h in diabetics ( P Ͻ 0.001). LTTH was increased 2 h postprandially by 190% in controls and by only 89% in diabetics, resulting in a 35% lowering of the LTTH area under the curve in diabetics. Postprandial LTTH was inversely correlated with TG or remnant concentrations in controls but not in diabetics, and with insulin resistance in both groups.These data show that TRL-bound LPL activity increases in the postprandial state and is strongly reduced in type 2 diabetes, contributing to postprandial hypertriglyceridemia. Postprandial hypertriglyceridemia is a prominent feature of dyslipidemia in type 2 diabetes and is considered to be proatherogenic (1-3). Accumulation of remnants in the postprandial state is thought to constitute a cardiovascular risk factor in insulin-resistant subjects (4, 5). Postprandial plasma triglyceride (TG) concentration depends upon the balance between intestinal and hepatic production of TG-rich lipoproteins (TRLs) and plasma clearance of remnants and VLDL. However, the precise mechanisms in TG clearance are difficult to explore, because little is known concerning the time course of the changes in the postprandial activity of lipoprotein lipase (LPL), the main enzyme involved in plasma TG hydrolysis. Because the bulk of LPL is bound to the endothelium, the release of the enzyme through heparin injection must be achieved to permit the ex vivo measurement of total LPL activity (6). In addition to being cumbersome, this process causes a prolonged release of LPL stores, which precludes any relevant time course study of LPL activity. However, several reports have described the presence of LPL protein in nonheparinized plasma (7-10). The mass concentration of the preheparinic LPL appeared to be negatively related to plasma TG concentration and positively related to HDL-cholesterol (HDL-C) (11,12). In addition, preheparinic LPL concentration was found to be increased after treatment with an insulin sensitizer, troglitazone (13), and decreased in situations in which TG catabolism was defective (14,15). Previous studies have shown that this plasma circulating LPL was bound to TRLs and exhibited some lipolytic activity (...

Hereditary Postprandial Hypertriglyceridemic Rabbit Exhibits Insulin Resistance and Central Obesity

“…28,29 In preliminary data, lipoprotein lipase activity of PHT rabbit was lower than that of JW rabbit (data not shown), marked increase of postprandial CM and VLDL TG in PHT rabbits may be strongly caused by decreasing lipoprotein lipase activity. Plasma NEFA levels were significantly higher in PHT rabbits than in JW rabbits, and preprandial plasma TG levels were also significantly higher in PHT rabbits (Figures 2, 3).…”

Postprandial dysmetabolism: Too early or too late?

“…34 It is likely that reduced LPL activity contributes to postprandial increase of TG in diabetic patients. 35 Regarding LPL, there is evidence that several modifiers may, through their interference, alter its activity, thus leading to TG accumulation. Specifically, ApoC-III, which is produced by the liver and intestine, is an exchangeable apolipoprotein located in the ApoA-I/C-III/A-IV gene cluster on chromosome 11q23.…”

Impact of bariatric surgery on apolipoprotein C-III levels and lipoprotein distribution in obese human subjects

“…5 Moreover, reduced activity of LPL has been shown in insulin-resistant subjects compared with control subjects in fasting and postprandial states. 47,48 This reduction in lipolytic activity seems also to be related to insulin resistance, insulin being a potent activator of LPL. 49 In the present study, the marked improvement in insulin sensitivity after bariatric surgery and its effects on TRL production and LPL activity could explain the decrease in plasma TG concentrations.…”