Postprandial Lipoprotein Levels Research Articles

A modified clot-based assay to measure negatively charged procoagulant phospholipids

Growing evidence supports a role for extracellular vesicles (EVs) in haemostasis and thrombosis due to exposure of negatively charged procoagulant phospholipids (PPL). Current commercial PPL-dependent clotting assays use chemically phospholipid depleted plasma to measure PPL activity. The purpose of our study was to modify the PPL assay by substituting the chemically phospholipid depleted plasma with PPL depleted plasma obtained by ultracentrifugation This in order to get readily access to a sensitive and reliable assay to measure PPL activity in human plasma and cell supernatants. The performance of the assay was tested, including the influence of individual coagulation factors and postprandial lipoproteins and compared to a commercial PPL assay (STA-Procoag-PPL). The two PPL assays displayed similar sensitivity to exogenously added standardized phospholipids. The PPL activity measured by the modified assay strongly correlates with the results from the commercial assay. The intraday- and between-days coefficients of variation ranged from 2–4% depending on the PPL activity in the sample. The modified PPL assay was insensitive to postprandial lipoprotein levels in plasma, as well as to tissue factor (TF) positive EVs from stimulated whole blood. Our findings showed that the modified assay performed equal to the comparator, and was insensitive to postprandial lipoproteins and TF+ EVs.

Effects of gemigliptin, a dipeptidyl peptidase-4 inhibitor, on lipid metabolism and endotoxemia after a high-fat meal in patients with type 2 diabetes.

We aimed to investigate the effects of gemigliptin, a dipeptidyl peptidase-4 inhibitor, on postprandial lipoprotein levels and endotoxemia in a randomized, double-blind, placebo-controlled, crossover study. Ten people with type 2 diabetes mellitus (T2DM), inadequately controlled with oral antidiabetic medications and/or lifestyle modification, were randomized to gemigliptin or placebo for 4 weeks. At the end of each treatment phase, the study participants underwent a high-fat meal tolerance test and needle aspiration of abdominal subcutaneous adipose tissue. The median (range) fasting and total area under the curve of apolipoprotein B48 (ApoB48) were significantly lower with gemigliptin than with placebo (2.9 [1.5-15.8] µg/mL vs 4.2 [1.3-23.4] µg/mL; P = .020; 35.3 [14.4-87.4] µg/mL × hour vs 42.2 [17.5-109.0] µg/mL × hour; P = .020, respectively), whereas apolipoprotein B100 showed no significant difference. Serum endotoxin levels were undetectable in 70% of the samples, so we were not able to evaluate the effect of gemigliptin on endotoxemia. The gene expression of inflammatory cytokines in subcutaneous adipose tissue was not affected by gemigliptin. Gemigliptin reduced ApoB48 levels after a high-fat meal in participants with T2DM. Whether systemic endotoxin levels can be reduced by gemigliptin requires further investigation.

Lipoprotein effects of incretin analogs and dipeptidyl peptidase 4 inhibitors.

Elevated post-prandial lipoprotein levels are common in patients with type 2 diabetes. Post-prandial lipoprotein alterations in type 2 diabetics are widely believed to drive inflammation and are considered a major risk factor for cardiovascular disease in diabetic patients. The incretins glucagon like peptide-1 (GLP-1) and glucose insulinotropic peptide (GIP) modulate post-prandial lipoproteins through a multitude of pathways that are independent of insulin and weight loss. Evidence from both animal models and humans seems to suggest an important effect on triglyceride rich lipoproteins (Apo48 containing) with little to no effects on other lipoproteins at least in humans. Dipeptidyl peptidase-4 (DPP4) inhibitors also appear to share these effects suggesting an important role for incretins in these effects. In this review, we will summarize lipid modulating effects of incretin analogs and DPP-4 inhibitors in both animal models and human studies and provide an overview of mechanisms responsible for these effects.

Effect of sitagliptin therapy on postprandial lipoprotein levels in patients with type 2 diabetes

Recent studies indicate that type 2 diabetes is associated with an increased secretion of both hepatic and intestinal lipoproteins, leading to the accumulation of atherogenic triglyceride (TG)-rich lipoproteins. Sitagliptin is a selective inhibitor of dipeptidyl peptidase-4 that has been shown to reduce fasting and postprandial glucose levels in patients with type 2 diabetes presumably through incretin hormone-mediated improvements in islet function. The objective of the present study is to examine the effects of treatment with sitagliptin on postprandial lipid and incretin hormone levels as well as glucose homeostasis in patients with type 2 diabetes. Thirty-six subjects with type 2 diabetes (30 men/6 postmenopausal women with a mean age of 58.1 ± 6.4 years and a body mass index of 30.7 ± 4.9 kg/m(2) ) were recruited in this double-blind cross-over study using sitagliptin 100 mg/day or placebo for a 6-week period each, with a 4-week washout period between the two phases. At the end of each phase of treatment, patients underwent an oral lipid tolerance test providing 35 g of fat per m(2) of body surface area and blood samples were taken over an 8-h period. Sitagliptin therapy significantly decreased the postprandial area under the curves (AUCs) for plasma apolipoprotein (apo)B (-5.1%, p = 0.002), apoB-48 (-7.8%, p = 0.03), TG (-9.4%, p = 0.006), very low-density lipoprotein (VLDL)-cholesterol (-9.3%, p = 0.001), free fatty acids (FFAs) (-7.6%, p = 0.005) and glucose (-9.7%, p < 0.0001). Furthermore, the postprandial AUCs for plasma intact glucagon-like peptide-1 (+67.8%, p < 0.0001) and glucose-dependent insulinotropic polypeptide (+67.3%, p < 0.0001) were significantly increased following treatment with sitagliptin, whereas the AUC for plasma glucagon was reduced by -9.7% (p = 0.001) with no significant changes in the AUCs for plasma insulin and C-peptide. Sitagliptin therapy also improved homeostasis model assessment (HOMA) index for insulin resistance (-14.6%, p = 0.01) and β-cell function (+32.3%, p = 0.007). Treatment with sitagliptin for 6 weeks reduced postprandial plasma levels of TG-rich lipoproteins of both intestinal and hepatic origin, most likely by increasing incretin hormone levels, reducing circulating plasma FFA concentrations and improving insulin sensitivity and β-cell function.

Th-W56:2 Clinical studies on biomarkers

The effect of a single oral fat meal (60 g fat/m2 body surface area) enriched in either saturated (SFA) or polyunsaturated ([PUFA] ω-6 or ω-3) fatty acids on postprandial lipoprotein levels was studied in four men with primary hypoalphalipoproteinemia (HP) and in four-age- and sex-matched controls. Vitamin A was included in the meal to label intestinally derived triglyceride-rich particles (TRP) with retinyl palmitate (RP). The HP subjects were either mildly hypertriglyceridemic (group A) or normotriglyceridemic (group B) and were phenotyped for post-heparin lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activities and apolipoprotein (apo) E isoforms. Postprandial total plasma triglyceride (TG), high-density lipoprotein (HDL) cholesterol, and RP and TG concentrations in the chylomicron (Sf > 1,000) and nonchylomicron (Sf > 1,000) fractions were evaluated for 24 hours after the meal. At each time point, HDL composition and size and apolipoprotein distributions were also measured. Following the SFA meal, HP subjects had maximal plasma TG levels at 8 hours (4 hours in controls) with a slow return to baseline levels at 12 to 24 hours (8 to 12 hours for controls). In contrast, after the ω-6 meal plasma TG levels decreased in group A subjects, while group B subjects and controls showed only a small increase. The results after the ω-7 meal were intermediate between the SFA and the ω-3 meal. When compared with group B, subjects in group A showed higher levels of RP-associated TRP, slower clearance rates, 30% to 50% lower fasting LPL activity, and 1.5-fold to twofold higher fasting plasma apo C-III levels. The major preprandial HDL subclass in HP subjects was HDL3, which showed a relative decrease in cholesterol esters (CE) and an increase in TG levels following the SFA meal. After the ω-3 meal, HDL of group A subjects showed a decrease in TG, a reciprocal increase in CE, and either no changes or minor changes in phospholipid (PL) and free-cholesterol (FC) levels. The results show that HP subjects with mild preprandial hypertriglyceridemia respond to a single fat meal differently than subjects with normotriglyceridemia, and that this difference is the result of HP in addition to other factors such as low LPL and HTGL activities, high plasma apo C-III levels, and apo E2 phenotype.

SMALL EFFECTS OF LINSEED OIL OR FISH OIL SUPPLEMENTATION ON POSTPRANDIAL CHANGES IN HEMOSTATIC FACTORS

Fish oils decrease alimentary lipemia [ 1 HARRIS W.S CONNOR W.E ALAM N ILLINGWORTH D.R Reduction of postprandial triglyceridemia in humans by dietary n-3 fatty acids. J Lipid Res. 1988; 29: 1451-1460 PubMed Google Scholar , 2 WEINTRAUB M.S ZECHNER R BROWN A EISENBERG S BREWSLOW J.L Dietary polyunsaturated fats of the w-6 and w-3 series reduce postprandial lipoprotein levels. J Clin Invest. 1988; 82: 1884-1893 Crossref PubMed Scopus (287) Google Scholar ]. This effect may be one of the protective mechanisms of fish or fish oils against coronary heart disease because postprandial lipid metabolism is involved in atherogenesis [ 3 ZILVERSMITH D.B Atherogenesis: a postprandial phenomenon. Circulation. 1979; 60: 473-485 Crossref PubMed Scopus (1423) Google Scholar ]. The modulation of lipemia has been attributed to the long-chain n-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3). To our knowledge, the effects of α-linolenic acid (ALA, 18:3 n-3), the precursor of EPA, have not been studied.

Bezafibrate therapy in patients with isolated low high-density lipoprotein cholesterol levels may have a beneficial effect in prevention of atherosclerosis

Although a low plasma high-density lipoprotein cholesterol (HDL-C) level is a well-accepted risk factor for coronary artery disease (CAD), it is unclear whether pharmacologic agents can effectively increase HDL-C levels and/or reduce the incidence of CAD in patients with isolated low HDL-C levels. An important determinant of HDL levels is the efficiency of postprandial lipoprotein catabolism. The purpose of the present study was to evaluate the efficacy of bezafibrate therapy in increasing HDL-C levels in these patients and to examine its effect on postprandial lipoprotein levels. Fasting and postprandial lipid and lipoprotein levels were studied in 23 patients with isolated low HDL-C levels before and during 3 and 6 months of bezafibrate treatment. Postprandial lipoprotein levels were evaluated using the vitamin A—fat loading test, in which these intestinally derived lipoproteins are specifically labeled with retinyl palmitate (RP). Patients with isolated low HDL had significantly higher levels of chylomicron RP than a control group of 19 normolipidemic subjects. The area below the chylomicron RP curve was 17,773 ± 6,821 versus 13,936 ± 6,217 μg/L · h, respectively ( P < .005). No differences were found in chylomicron remnant levels between the groups. Bezafibrate therapy reduced the chylomicron RP area by 27%, from 17,773 ± 6,821 to 12,895 ± 2,576, and the nonchylomicron RP area by 25%, from 6,059 ± 3,310 to 4,430 ± 1,963 ( P < .0001). It increased fasting HDL-C levels from 35 ± 3 to 38 ± 1.4 mg/dL after 3 months ( P < .001) and to 40 ± 2.2 mg/dL after 6 months ( P < .001). A highly significant inverse correlation ( r = .8885, P < .001) was found between fasting HDL-C and postprandial chylomicron RP levels. The patients did not respond to therapy as a homogenous group. That is, eight patients did not respond to bezafibrate either by reducing postprandial lipoprotein levels or by increasing HDL-C levels, bezafibrate in these patients did significantly reduce low-density lipoprotein cholesterol (LDL-C) levels from 138 ± 4.8 to 125 ± 5.9 mg/dL ( P < .0001) while the patients were on a strict low-fat, low-cholesterol diet. In conclusion, most patients with isolated low HDL-C levels also have a defect in postprandial lipoprotein metabolism. Bezafibrate therapy has a dual effect: it reduces the level of these possibly atherogenic lipoproteins and increases HDL-C levels. These findings support the use of bezafibrate therapy in high-risk patients with isolated low HDL-C levels.

Effects of purified docosahexaenoic acid on fasting and postprandial lipoprotein levels in normolipidemic volunteers

Effects of purified docosahexaenoic acid on fasting and postprandial lipoprotein levels in normolipidemic volunteers

Comparison of the effects of interesterified butter oil, natural butter oil, rapeseed oil and sunflower oil on postprandial lipoprotein levels in healthy women

Comparison of the effects of interesterified butter oil, natural butter oil, rapeseed oil and sunflower oil on postprandial lipoprotein levels in healthy women

Hypoalphalipoproteinemia: Postprandial response of subjects with preprandial normotriglyceridemia and hypertriglyceridemia to various diets

The effect of a single oral fat meal (60 g fat/m 2 body surface area) enriched in either saturated (SFA) or polyunsaturated ([PUFA] ω-6 or ω-3) fatty acids on postprandial lipoprotein levels was studied in four men with primary hypoalphalipoproteinemia (HP) and in four-age- and sex-matched controls. Vitamin A was included in the meal to label intestinally derived triglyceride-rich particles (TRP) with retinyl palmitate (RP). The HP subjects were either mildly hypertriglyceridemic (group A) or normotriglyceridemic (group B) and were phenotyped for post-heparin lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activities and apolipoprotein (apo) E isoforms. Postprandial total plasma triglyceride (TG), high-density lipoprotein (HDL) cholesterol, and RP and TG concentrations in the chylomicron (S f > 1,000) and nonchylomicron (S f > 1,000) fractions were evaluated for 24 hours after the meal. At each time point, HDL composition and size and apolipoprotein distributions were also measured. Following the SFA meal, HP subjects had maximal plasma TG levels at 8 hours (4 hours in controls) with a slow return to baseline levels at 12 to 24 hours (8 to 12 hours for controls). In contrast, after the ω-6 meal plasma TG levels decreased in group A subjects, while group B subjects and controls showed only a small increase. The results after the ω-7 meal were intermediate between the SFA and the ω-3 meal. When compared with group B, subjects in group A showed higher levels of RP-associated TRP, slower clearance rates, 30% to 50% lower fasting LPL activity, and 1.5-fold to twofold higher fasting plasma apo C-III levels. The major preprandial HDL subclass in HP subjects was HDL 3, which showed a relative decrease in cholesterol esters (CE) and an increase in TG levels following the SFA meal. After the ω-3 meal, HDL of group A subjects showed a decrease in TG, a reciprocal increase in CE, and either no changes or minor changes in phospholipid (PL) and free-cholesterol (FC) levels. The results show that HP subjects with mild preprandial hypertriglyceridemia respond to a single fat meal differently than subjects with normotriglyceridemia, and that this difference is the result of HP in addition to other factors such as low LPL and HTGL activities, high plasma apo C-III levels, and apo E2 phenotype.

Triglyceride-rich lipoproteins and atherosclerosis, from fast to feast.

There is increasing evidence that fasting hypertriglyceridaemia identifies individuals who are at increased risk for coronary artery disease. It is probable that this reflects the effects of the smaller triglyceride-bearing lipoproteins. It may also reflect increased levels of postprandial lipoproteins. There is considerable theoretical and experimental evidence to support an atherogenic role for the smaller, triglyceride-rich postprandial lipoproteins. Cross-sectional studies in humans also indicate that those with coronary disease have increased levels of postprandial lipids, probably in the remnants of chylomicrons. Recently we have completed a study examining the progression of coronary atherosclerosis angiographically. The study showed that the progression was linearly related to the numbers of chylomicron remnant particles, as reflected by the quantity of apoB48 in Sf20-60 lipoproteins, in the postprandial circulation. This paper reviews these studies, the physiology of postprandial lipoprotein metabolism and the therapeutic implications of this information.

Lovastatin reduces postprandial lipoprotein levels in hypercholesterolaemic patients with mild hypertriglyceridaemia

Drugs that inhibit cholesterol synthesis have recently been released for lowering LDL-cholesterol levels. The current study examines the effect of one of these drugs, lovastatin, alone and in combination with cholestyramine on postprandial fat metabolism in five patients with severely elevated LDL-cholesterol and normal triglyceride levels (less than 1.8 mmol l-1) and in five patients with similarly elevated LDL-cholesterol and mildly elevated triglyceride levels (1.8 to 2.7 mmol l-1). In the group of patients with normal triglyceride levels, neither lovastatin alone nor in combination with cholestyramine had any effect on postprandial lipoprotein levels, while profoundly decreasing LDL-cholesterol levels. This provides evidence that LDL and postprandial lipoproteins are cleared by different mechanisms. In the group of five patients with mildly elevated triglyceride levels, in addition to LDL-cholesterol lowering, lovastatin significantly lowered VLDL-cholesterol, fasting triglyceride and postprandial lipoprotein levels. Thus in patients with mild hypertriglyceridaemia, lovastatin may have another favourable effect on the lipoprotein system in addition to LDL-cholesterol lowering.

Physical exercise conditioning in the absence of weight loss reduces fasting and postprandial triglyceride-rich lipoprotein levels.

The effect of physical exercise conditioning on fasting and postprandial lipoprotein levels was studied in six normolipidemic subjects. The study consisted of two phases: a baseline stabilization phase in which subjects maintained their regular physical activity and an exercise conditioning phase in which subjects had 29 exercise sessions during a 7-week period. Each of these sessions consisted of jogging on a treadmill for 30 minutes. The subjects averaged 15.2 miles/wk. To control for possible confounding factors, such as changes in diet composition and weight loss, we placed the subjects on a metabolic diet and increased their daily caloric intake during the exercise phase. At the end of each phase of the study, a vitamin A-fat loading test was done to specifically label and follow postprandial lipoprotein levels, and a maximum oxygen consumption test was done to evaluate the subjects' physical fitness. The exercise conditioning phase significantly increased the subjects' aerobic capacity and postheparin lipoprotein lipase activity, and the phase decreased fasting triglyceride levels. Physical exercise also significantly decreased chylomicron (Sf greater than 1,000) levels by 37%. In summary, this study suggests that physical exercise conditioning reduces fasting and postprandial lipoprotein levels by increasing the catabolism of triglyceride-rich particles. Because these particles may have a role in atherogenesis, this could be a major mechanism by which exercise prevents coronary heart disease.

Dietary polyunsaturated fats of the W-6 and W-3 series reduce postprandial lipoprotein levels. Chronic and acute effects of fat saturation on postprandial lipoprotein metabolism.

The chronic and acute effects of different types of dietary fat on postprandial lipoprotein metabolism were studied in eight normolipidemic subjects. Each person was placed for 25 d on each of three isocaloric diets: a saturated fat (SFA), a w-6 polyunsaturated fat (w-6 PUFA) and a w-3 polyunsaturated fat (w-3 PUFA) diet. Two vitamin A-fat loading tests were done on each diet. The concentrations in total plasma and chylomicron (Sf greater than 1,000) and nonchylomicron (Sf less than 1,000) fractions of retinyl palmitate (RP) were measured for 12 h postprandially. Compared with the SFA diet, the w-6 PUFA diet reduced chylomicron and nonchylomicron RP levels 56 and 38%, respectively, and the w-3 PUFA diet reduced these levels 67 and 53%, respectively. On further analysis, the main determinant of postprandial lipoprotein levels was the type of fat that was chronically fed, which appeared to mediate its effect by changing the concentration of the endogenous competitor for the system that catabolizes triglyeride-rich lipoproteins. However, there was a significant effect of the acute dietary fat load, which appeared to be due to a differential susceptibility to lipolysis of chylomicrons produced by SFA as opposed to PUFA fat loads. The levels of postprandial lipoproteins are determined by the interaction of these chronic and acute effects.