Postprandial Lipoprotein Responses Research Articles

A variant near the melanocortin-4 receptor gene regulates postprandial lipid metabolism in a healthy Caucasian population

The melanocortin-4 receptor (MC4R) is an essential regulator of food intake and energy homeostasis. Previous data suggest an influence of MC4R activity on TAG levels. Thus, the aim of the present study was to determine whether the presence of the rs12970134 polymorphism near the MC4R gene could influence postprandial lipoprotein metabolism in healthy subjects. A total of eighty-eight volunteers were selected, fifty-three homozygous for the common genotype (G/G) and thirty-five carriers for the minor A-allele (G/A and A/A). They were given a fat-rich meal containing 1 g fat and 7 mg cholesterol/kg body weight and vitamin A (60,000 IU/m(2) body surface). Fat accounted for 60 % of energy, and protein and carbohydrates accounted for 15 and 25 % of energy, respectively. Blood samples were taken at time 0, every 1 h until 6 h and every 2·5 h until 11 h. Total cholesterol and TAG in plasma, and cholesterol, TAG and retinyl palmitate in TAG-rich lipoproteins (TRL, large and small TRL) were separated by ultracentrifugation. Individuals carrying the G/G genotype displayed a higher postprandial response of plasma TAG (P = 0·033), total cholesterol (P = 0·019) and large TRL-TAG (P = 0·023) than did carriers of the minor A-allele. Furthermore, G/G subjects showed a greater postprandial response of small TRL-apoB48 than did carriers of the A-allele (P = 0·032). These results suggest that the rs12970134 polymorphism near the MC4R gene region may partly explain the inter-individual differences in postprandial lipoprotein response in healthy subjects.

Heterogeneous Postprandial Lipoprotein Responses in the Metabolic Syndrome, and Response to Fenofibrate Therapy

Hypertriglyceridemia subjects with metabolic syndrome exhibit variable postprandial triglyceride responses. We investigate the effects of fenofibrate therapy on postprandial triglyceride-containing lipoproteins in subjects with early (3.5h) versus late (8h) postprandial triglyceride responses. Fifty-five subjects with fasting hypertriglyceridemia (≥1.7mmol/L (150mg/ dL) and <5.8mmol/L (500mg/dL)) and ≥2 Adult Treatment Panel III criteria of the metabolic syndrome were randomized to daily fenofibrate (160mg/d) or placebo for 12weeks in a double-blind controlled clinical trial. A standardized fat load (50g/m(2)) was given orally after a 12h fast. Blood specimens were obtained at 0h (fasting), 3.5h, and 8h after the test meal. Analysis is confined to the 53 subjects with clearly identifiable early or late triglyceride peaks prior to therapy. Fenofibrate was more effective in late peakers (n = 8) when compared to early peakers (n = 15) with respect to reducing postprandial triglyceride concentrations (-67% vs. -34%, p = 0.0024) and large VLDL (-76% vs. -31%, p = 0.0016), and increasing total HDL particles (20% vs. 11%, p = 0.008) and large HDL particles (185% vs. 88%, p = 0.003). On fenofibrate therapy, 100% of those initially designated as late peakers were reclassified as early peakers; 47% of late peakers assigned to placebo were reclassified as early peakers. Late postprandial triglyceride responders have attenuated clearance of large VLDL particles, but they were more responsive to fenofibrate.

Body mass interacts with fat quality to determine the postprandial lipoprotein response in healthy young adults

Background and aimsPostprandial lipemia predicts the evolution of cardiovascular disease. Obesity is associated with an increase in the magnitude of postprandial lipemia. Our objective was to evaluate the influence of body mass index (BMI) on the effects of acute ingestion of different types of fat on the postprandial lipemic response. Methods and resultsTwenty-one healthy men followed a 4-week baseline diet and then consumed three fat-loaded meals that included 1g fat/kg body wt (65%fat) according to a randomized crossover design. The compositions of the three meals were olive oil meal (22% saturated fatty acids (SFA), 38% monounsaturated fatty acids (MUFA), 4% polyunsaturated fatty acids (PUFA)); butter meal (35% SFA, 22% MUFA, 4% PUFA); walnuts meal (20% SFA, 24% MUFA, 16% PUFA, and 4% α-linolenic acid). Higher-weight (HW) subjects (BMI greater than the median 26.18kg/m2, n=11) presented higher incremental area under the curve (iAUC) for triglycerides (TG), both in large- and small-TG rich lipoproteins (TRL) than lower-weight (LW) subjects (BMI<26.18kg/m2, n=10) (p<0.05), and a similar trend for plasma TG (p=0.084). Moreover, HW subjects presented higher concentrations for small TRL-cholesterol and small TRL-TG in different timepoints of the postprandial lipemia after the intake of enriched walnuts or butter meals compared with the olive oil-enriched meal (p<0.05) No significant differences were observed between the three types of meals in the postprandial response of LW subjects. ConclusionHW subjects present a greater postprandial response than LW subjects, and they benefit from the consumption of monounsaturated fatty acids from olive oil, to lower their levels of TRL particles during the postprandial state.

Influence of Aging and Menopause on Postprandial Lipoprotein Responses in Healthy Adult Women

To analyze the influence of menopause and age on postprandial lipoprotein responses in healthy adult women. Twenty-seven healthy young and middle-aged pre- and postmenopausal female volunteers aged 21-53 y were enrolled. They ingested OFTT cream(Jomo, Takasaki, Japan). Fasting and postprandial blood samples were obtained for up to 6 h, and serum concentrations of lipoproteins were analyzed. In the postprandial phase, serum triglycerides(TG), remnant-like particle(RLP)-TG(RLP-TG), RLP-cholesterol(RLP-C), and TG-rich lipoprotein-TG(TRL-TG)concentrations in all groups peaked after 2 h. After 4 h, the TG, RLP-C, RLP-TG and TRL-TG concentrations in the young women returned to the fasting concentrations. However, at 6 h, these parameters in the pre- and postmenopausal women had barely returned to the fasting concentrations. The present results suggest that:(1)the magnitude of postprandial TG concentrations is dependent on age, but not on menopause;(2)clearance of remnant lipoproteins is delayed with age in pre- and postmenopausal women compared to young women, and(3)menopause is associated with an increase of RLP-C, but may not influence LDL particle size.

Differential Postprandial Lipoprotein Responses in Type 2 Diabetic Men with and without Clinical Evidence of a Former Myocardial Infarction

Postprandial lipemia plays an important role in the development of coronary heart disease through an elevation of triglyceride-rich lipoproteins. In type 2 diabetic male subjects, our aim was to compare postprandial lipemia in a high-risk population with former myocardial infarction (MI) with that of a lower risk population free of clinically detectable heart disease. 32 male type 2 diabetic subjects were included in the study. We matched 17 cases with a verified history of MI with 15 controls according to age, BMI, HbA1c, diabetes duration, smoking, and treatment of diabetes. Ongoing metformin, insulin, or lipid lowering pharmacological treatment were exclusion criteria. After a maximal exercise tolerance test and echocardiography, the subjects underwent a hyperinsulinemic, euglycemic clamp and a vitamin A fat loading test. Plasma triglyceride levels in the case group were significantly higher after 360 minutes (4.6 +/- 3.1 vs. 2.8 +/- 1.8 mmol/l, p = 0.04) and 480 minutes (3.6 +/- 2.2 vs. 2.4 +/- 2.4 mmol/l, p = 0.03), as was the incremental Area Under the Curve (iAUC) for the whole period (560 +/- 452 vs. 297 +/- 214 mmol x 480 min./l; p = 0.048). In addition, the retinyl palmitate responses in the chylomicron-fraction from the case group were significantly higher (iAUC 311,502 +/- 194,933 vs. 187,004 +/- 102,928 ng x 480 min./ml; p = 0.035). Type 2 diabetic males with prior MI had higher postprandial triglyceride-rich lipoprotein responses than those without MI, indicating that high responses may be a marker for a high-risk population.

Influence of mental stress and circadian cycle on postprandial lipemia

Mental stress produces alterations in serum lipids and lipoproteins. The objective was to assess the effect of mental stress during the day and night on postprandial lipoproteins. Fourteen healthy subjects aged 26.6 +/- 5.0 y were given randomly the same meal either at night (0100) or during the day (1300), with or without (control session) a mental stress challenge. The meal contained 40% of estimated daily energy needs. The mental task was performed on a computer and consisted of a task of choice reaction. Blood samples were drawn at baseline and hourly for 7 h after the meal. Urinary epinephrine concentrations were higher (P < 0.012) during the mental task than during the control sessions. Repeated-measures analysis of variance showed that mean postprandial triacylglycerol concentrations were significantly higher (P < 0.02) and total cholesterol (P < 0.0001) and HDL-cholesterol concentrations were significantly lower (P < 0.0001) at night than during the day. The mean postprandial VLDL-triacylglycerol concentration was significantly higher (P < 0.04) during the mental task than during the control sessions. Similarly, the VLDL-cholesterol response, calculated as the area under the postprandial curve, was significantly greater (P < 0.02) during the mental task than during the control sessions. There was no interaction between mental stress and nyctohemeral cycle on postprandial lipoprotein responses, suggesting that both indexes act independently on postprandial lipid metabolism. Mental stress is associated with increased concentrations of postprandial triacylglycerol-rich lipoprotein fractions. Therefore, postprandial hyperlipidemia is one possible mechanism contributing to the higher risk of ischemic heart disease in stressed people.

Dietary interventions affecting chylomicron and chylomicron remnant clearance

Interest in effects of diet on postprandial lipoproteins has increased in recent years as a result of accumulating evidence for adverse cardiovascular consequences of elevated concentrations of triglyceride rich lipoproteins. Particular attention has been given to ability of different fatty acids to modulate postprandial lipoprotein responses because of evidence for both harmful and protective cardiovascular properties of the saturated, monounsaturated and ω-6 and ω-3 polyunsaturated fatty acid (PUFA) classes. Evidence for direct atherogenic properties of chylomicron remnants has led to attempts to monitor effects of diet specifically on this lipoprotein class. Limitations in the methods employed to measure chylomicron remnants and the small number of human studies which have evaluated effects of meal, and background diet, fatty acid composition, makes it difficult to draw definitive conclusions at the present time. However consideration of data from both animal and human studies tends to support the conclusion that diets, and meals, rich in PUFA (particularly long chain ω-3 PUFA), result in attenuated postprandial responses of the intestinally-derived lipoproteins. Attenuated responses to high PUFA meals appear to be due to greater rates of clearance and greater activation of lipoprotein lipase (LPL). Attenuated responses to high PUFA background diets may be due to adaptive changes involving both accelerated rates of clearance in peripheral tissues and liver, as well as decreased output of the competitor for chylomicron clearance, very low density lipoprotein (VLDL).

Assessment of postprandial lipemia: nutritional influences.

Recent reports have contributed new information on the influence of the size and spacing of fat-containing meals on processes related to fat digestion and absorption, lymphatic transport, and postprandial responses of plasma lipoproteins. The postabsorptive concentrations of plasma triglycerides and common polymorphisms of apolipoprotein B and apolipoprotein E exert important influences on postprandial lipoprotein responses. Attention to these characteristics of individuals and groups can facilitate interpretation of responses to meals containing different fatty acids and varying amounts of cholesterol. Additional evidence is accumulating that points to disease related abnormalities of postprandial lipoprotein metabolism related to clearance mechanisms for triglyceride-rich lipoproteins and processes related to reverse cholesterol transport.

Postprandial lipoprotein responses in hypertriglyceridemic subjects with and without cardiovascular disease

Three groups of age- and weight-matched men (aged 40 to 70 years) without diabetes were studied: controls (n = 10), plasma triglycerides (TG) less than 180 mg/dL and no cardiovascular disease (CVD); HTG — CVD (n = 11), hypertriglyceridemic (HTG) (TG > 240 mg/dL) without CVD; and HTG + CVD (n = 10), HTG (TG > 240 mg/dL) with documented CVD. HTG + CVD subjects had higher fasting and post-oral glucose tolerance test insulin levels than the other two groups, respectively. Very—low-density lipoprotein (VLDL) + chylomicrons (CMs), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and three high-density lipoprotein (HDL) subfractions (HDL-L, HDL-M, and HDL-D, from least to most dense) were isolated by gradient ultracentrifugation. Fasting lipoproteins were similar in HTG groups, except for higher VLDL lipid to apolipoprotein (apo) B ratios ( P < .04) in the HTG + CVD group. Subjects were fed a high-fat mixed meal, and lipoprotein composition was determined at 3, 6, 9, and 12 hours postprandially. Postprandial responses of the core lipids (TG and cholesterol esters ICE]) in all of the iipoprotein subfractions were similar in the two HTG groups at each time point. However, both controls and HTG — CVD subjects had increases in HDL-M phospholipid (PL) at 9 and 12 hours with no change in HDL-D PL. The HTG + CVD group, on the other hand, had no increase in HDL-M PL and had a substantial reduction in HDL-D PL. These changes resulted in significant increases in HDL-M and HDL-D PI. to apo A-I ratios in both controls and HTG — CVD subjects between 6 and 12 hours, whereas there was no increase seen in the HTG + CVD group. The HTG — CVD group also had a significantly greater increase in the VLDL + CM PL to apo B ratio ( P = .038) at 3 hours than the HTG + CVD group. This diminished amount of surface lipid per VLDL particle may account for the late decrease in the HDL-D PI. to apo A-I ratio seen in HTG + CVD patients. There were no other postprandial lipid or apolipoprotein differences between the two HTG groups. We conclude therefore that the major postprandial lipoprotein abnormality in these HTG + CVD patients was a failure to increase the PL content per particle in VLDL + CM, HDL-M, and HDL-D. This abnormality could prevent the usual increase in reverse cholesterol transport seen in postprandial plasma and therefore contribute to their increased incidence of CVD. The greater insulin resistance seen in these patients also appears to contribute significantly to their CVD.

Effects of increasing amounts of dietary cholesterol on postprandial lipemia and lipoproteins in human subjects.

Our aim was to determine the effects of increasing amounts of dietary cholesterol (0-710 mg) on the postprandial plasma lipid responses and lipoprotein changes in normolipidemic human subjects. Ten subjects were fed five different test meals in a random order: one meal did not contain fat or cholesterol while the four others contained a fixed amount of lipids (45 g) and 0, 140, 280, and 710 mg cholesterol, respectively. Fasting and post-meal blood samples were obtained for 7 h. Large and small triglyceride-rich lipoproteins (TRL), low density (LDL), and high density (HDL) lipoproteins were isolated. Compared to the no-fat, no-cholesterol meal, the fat-enriched meals raised (P < 0.05) plasma triglycerides, phospholipids, and free cholesterol and lowered cholesteryl esters postprandially. The meals containing zero or 140 mg cholesterol generally elicited comparable postprandial plasma and lipoprotein lipid responses. The meals providing 280 or 710 mg cholesterol significantly increased postprandial plasma phospholipids and large TRL triglycerides and decreased plasma esterified cholesterol. The lipid composition of the large TRLs and the concentrations of the small TRL lipid components were not altered postprandially by cholesterol intake. On the other hand, LDL free cholesterol increased after 3 h, LDL cholesteryl esters dropped after 3 and 7 h, HDL cholesteryl esters dropped after 3 h, and HDL phospholipids increased 7 h after ingesting meals highly enriched in cholesterol. Blood insulin, apoA-I and apoB were not altered postprandially by cholesterol intake. Thus, the data show that ingesting more than 140 mg cholesterol per meal significantly alters the postprandial lipoprotein response in healthy subjects.

Postprandial triglyceride response in Type 1 (insulin-dependent) diabetes mellitus is not altered by short-term deterioration in glycaemic control or level of postprandial insulin replacement

The effect of deteriorating glycaemic control on the lipoprotein responses to the ingestion of a high fat meal was investigated in seven normolipidaemic Type 1 (insulin-dependent) diabetic patients and the results were compared with corresponding responses in seven normolipidaemic control subjects. In addition, the importance of insulin in regulating the postprandial lipoprotein responses was examined by comparing the results obtained from the diabetic patients maintained on a basal infusion of insulin throughout the study with those obtained when a step-up, step-down insulin infusion was administered following the meal. Vitamin A was added to the test meal in all subjects to trace the metabolism of the chylomicron (Sf greater than 1000) and non-chylomicron (Sf less than 1000) fractions in the postprandial period. No differences in fasting and postprandial triglyceride levels nor in the concentration of the chylomicron and non-chylomicron fractions were observed between diabetic and control subjects. In the diabetic patients short-term (two-week) deterioration in glycaemic control did not have any adverse influence on the basal and postprandial lipid responses. However, while the amount of insulin administered after the meal in the diabetic patients did not have any effect on the postprandial triglyceride or chylomicron responses, the concentration of non-esterified fatty acids was significantly higher (p less than 0.0005) when only a basal infusion of insulin was administered. 1) Short-term deterioration in glycaemic control does not adversely affect lipoprotein concentrations in Type 1 diabetes. 2) Non-esterified fatty acids appear to be a more sensitive index of insulinization post-prandially than triglycerides.