Diagnosis, Outcome, and Management of Chylous Ascites Following Pediatric Liver Transplantation.

Data on postoperative chylous ascites (CA) after pediatric liver transplantation (LT) are scarce. This retrospective study was conducted to identify the incidence, risk factors, management, and outcomes of postoperative CA in a large single-center pediatric LT cohort (2000-2016). The study cohort comprised 317 LTs (153 living donors and 164 deceased donors) in 310 recipients with a median age of 2.7 years. The incidence of CA was 5.4% (n = 17), diagnosed after a median time of 10 days after LT. Compared with chylomicron detection in peritoneal fluid (the gold standard), a triglyceride cutoff value of 187 mg/dL in peritoneal fluid showed insufficient sensitivity (31%) for CA diagnosis. In univariate logistic regression analyses, ascites before LT, younger age, and lower weight, height, and height-for-age z score at LT were associated with CA. Symptomatic management of CA included peritoneal drain (100%) and diuretics (76%). Therapeutic interventions included very low-fat or medium-chain triglyceride-rich diets (94%) and intravenous octreotide (6%), leading to CA resolution in all patients. CA was associated with prolonged hospital length of stay (LOS; 40 days in the CA group versus 24 days in the non-CA group; P = 0.001) but not with reduced patient or graft survival rates after a median follow-up time of 14 years. In conclusion, CA in the pediatric LT recipient is a relatively uncommon complication associated with increased hospital LOS and morbidity. Measurement of chylomicrons is recommended in patients with ascites that is more severe or persistent than expected. Dietary interventions are effective in most patients.

Characterization of chylomicron in preterm infants.

BACKGROUND: The aim of this study was to investigate cholesterol and triglyceride levels in the chylomicron fraction of preterm infants at birth and during the early postnatal period. METHODS: The subjects consisted of 133 infants (81 boys and 52 girls): 74 were term infants born at 37-41 weeks of gestation and 59 were preterm infants born at 29-36 weeks of gestation. Cholesterol and triglyceride in the chylomicron fraction were measured using high-performance liquid chromatography. RESULTS: Compared with term infants, preterm infants had higher cholesterol and lower triglyceride in the chylomicron fraction, both in cord blood and at 1 month after birth. Thus, the chylomicron triglyceride/cholesterol ratio was significantly lower in preterm infants than in term infants in cord blood and at 1 month of age. On single regression analysis the chylomicron triglyceride/cholesterol ratio correlated positively with gestational age at birth (r = 0.331, P = 0.0003) and at 1 month (r = 0.221, P = 0.0119). CONCLUSIONS: Preterm infants have a less-lipidated chylomicron composition at birth and at 1 month of age. Some prenatal factors may persist to influence chylomicron lipidation during the early postnatal period.

Quilotórax en adultos. Revisión de la literatura a partir de una serie de 17 casos / Chylothorax in Adults. Characteristics of 17 Patients and a Review of the Literature

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Mecanismos básicos: estructura, función y metabolismo de las lipoproteínas plasm / No disponible

El objetivo de este capítulo es presentar información básica sobre la fisiología de las lipoproteínas. La fracción proteica de las lipoproteínas consta de varias apolipoproteínas y enzimas cuyas funciones son el transporte y la metabolización de los lípidos. La clasificación de las lipoproteínas se basa en su densidad y se pueden aislar por ultracentrifugación quilomicrones, VLDL, IDL, LDL y HDL. Los quilomicrones y las VLDL transportan los triglicéridos desde el intestino e hígado, respectivamente, hasta los tejidos periféricos. La metabolización de las VLDL origina las IDL y LDL. Las LDL transportan la mayoría del colesterol plasmático a los tejidos extrahepáticos. La HDL moviliza el colesterol de los tejidos periféricos hacia el hígado, donde se elimina en forma de colesterol libre o sales biliares, proceso conocido como transporte reverso de colesterol. El metabolismo de las lipoproteínas puede ser regulado por receptores nucleares que regulan la expresión de genes del metabolismo de triglicéridos y de las apolipoproteínas (AU)

The aim of this work is to present basic information on the lipoprotein physiology. The protein fraction of lipoproteins consists of several apolipoproteins and enzymes whose functions are lipid transport and metabolism. Classification of lipoproteins is based on their density. Chylomicrons, VLDL, IDL, LDL and HDL can be isolated by ultracentrifugation. Both chylomicrons- and VLDL-triglycerides are transported from the intestine and liver, respectively, to the peripheral tissues. The metabolism of VLDL originates IDL and LDL. LDL is the main transporter of cholesterol to extrahepatic tissues. HDL mobilizes cholesterol from peripheral tissues to the liver where it is secreted to bile as free cholesterol or bile salts, a process termed reverse cholesterol transport. Lipoprotein metabolism can be regulated by nuclear receptors that regulate the expression of genes involved in triglyceride and apolipoprotein metabolism (AU)

Modulating absorption and postprandial handling of dietary fatty acids by structuring fat in the meal: a randomized crossover clinical trial.

BACKGROUND: Prolonged postprandial hypertriglyceridemia is a potential risk factor for cardiovascular diseases. In the context of obesity, this is associated with a chronic imbalance of lipid partitioning oriented toward storage and not toward ß-oxidation. OBJECTIVE: We tested the hypothesis that the physical structure of fat in a meal can modify the absorption, chylomicron transport, and further metabolic handling of dietary fatty acids. DESIGN: Nine normal-weight and 9 obese subjects were fed 40 g milk fat (+[(13)C]triacylglycerols), either emulsified or nonemulsified, in breakfasts of identical composition. We measured the postprandial triacylglycerol content and size of the chylomicron-rich fraction, plasma kinetics of [(13)C]fatty acids, exogenous lipid oxidation with breath-test/indirect calorimetry, and fecal excretion. RESULTS: The emulsified fat resulted in earlier (>1 h) and sharper chylomicron and [(13)C]fatty acid peaks in plasma than in spread fat in both groups (P < 0.0001). After 2 h, the emulsified fat resulted in greater apolipoprotein B-48 concentrations (9.7 ± 0.7 compared with 7.1 ± 0.9 mg/L; P < 0.05) in the normal-weight subjects than did the spread fat. In the obese subjects, emulsified fat resulted in a 3-fold greater chylomicron size (218 ± 24 nm) compared with the spread fat (P < 0.05). The emulsified fat induced higher dietary fatty acid spillover in plasma and a sharper (13)CO(2) appearance, which provoked increased exogenous lipid oxidation in each group: from 45% to 52% in normal-weight subjects (P < 0.05) and from 40% to 57% in obese subjects (P < 0.01). CONCLUSION: This study supports a new concept of "slow vs fast fat," whereby intestinal absorption can be modulated by structuring dietary fat to modulate postprandial lipemia and lipid ß-oxidation in humans with different BMIs. This trial was registered at clinicaltrials.gov as NCT01249378.

Cell-based assay to quantify the antioxidant effect of food-derived carotenoids enriched in postprandial human chylomicrons.

We developed a new method to evaluate the antioxidant effect of food products in a biological system. The antioxidant status of HepG2 cells was quantified after incubation with postprandial human chylomicrons after the intake of vegetable products. Three subjects consumed in a meal a vegetable soup containing 8.4 mg of ß-carotene and 9 mg of lycopene. After 5 h, the subjects consumed a second meal without carotenoids. Blood samples were collected at basal time and every hour for 9 h. Chylomicrons were isolated from serum samples and used for both carotenoid quantification and HepG2 stimulation. Carotenoid in chylomicrons followed an inter-individual and bimodal carotenoid response. We demonstrated the antioxidant effect of postprandial chylomicrons in HepG2 at the time of maximum carotenoid concentration of chylomicrons with respect to basal time. This cell-based assay seems to be a useful method to evaluate the antioxidant effect of fruit and vegetable products in a biological system.

Analysis of cholesterol levels in lipoprotein(a) with anion-exchange chromatography.

We previously established an analysis method for determining the cholesterol levels of five major lipoprotein classes [HDL, LDL, intermediate density lipoprotein (IDL), VLDL, and chylomicrons] in serum by an anion-exchange (AEX)-HPLC method, but lipoprotein(a) [Lp(a)], a well-known risk factor for atherosclerotic diseases, was not determinable. Therefore, we established new AEX-HPLC separation conditions for analyzing the cholesterol levels of six lipoprotein classes, including Lp(a). Serum lipoproteins were separated by HPLC with a diethylaminoethyl-ligand nonporous polymer-based column by elution with a stepwise gradient of the sodium perchlorate concentration. In this improved method, HDL, LDL, IDL, VLDL, chylomicrons, and Lp(a) were each eluted from the column. The cholesterol levels of the eluted lipoproteins were measured enzymatically by a postcolumn reaction. The within-day assay and between-day assay coefficients of variation for the lipoprotein cholesterol levels were in the ranges of 0.29-11.86% and 0.57-11.99%, respectively. The Lp(a) cholesterol levels determined by AEX-HPLC were significantly correlated with the amounts of Lp(a) protein measured by an immunoturbidimetry method available commercially (r = 0.9503, P < 0.0001). Taken together, this AEX-HPLC method may be effectively applied to the analysis of serum lipoproteins with high levels of Lp(a).

Vitamin A concentrations in piglet extrahepatic tissues respond differently ten days after vitamin A treatment.

Periodic supplementation to infants and young children is encouraged in developing countries by the WHO. We investigated vitamin A (VA) in extrahepatic tissues of piglets after supplementation with retinyl acetate to determine long-term storage. 3, 4-Didehydroretinyl acetate (DRA) as a tracer was used to evaluate uptake from chylomicra in 4 h. Sows were fed a VA-depleted diet throughout pregnancy and lactation. Male castrated piglets (n = 28, 11.6 +/- 0.5 d) from these sows were weaned onto a VA-free diet for 1 wk, assigned to 4 groups, and dosed orally with 0, 26.2, 52.4, or 105 micromol VA. After 10 d, 5.3 micromol DRA was administered to determine short-term uptake of 3, 4-didehydroretinol (DR). Four hours later, piglets were killed; adrenal glands, kidney, lung, and spleen were collected and analyzed for retinol and DR. Retinol concentrations of kidney and adrenal gland were higher than control, but treated groups did not differ. Retinol concentration was highest in kidney (1.70-2.52 nmol/g), followed by adrenal gland (0.30-0.48 nmol/g), lung (0.15-0.21 nmol/g), and spleen (0.11-0.15 nmol/g). Total retinol in kidney and spleen was different among the groups (P < 0.05). Unesterified retinol was the major VA form; the percent retinol of total VA was lowest in adrenal glands. DR did not differ among the groups. In 4 h, the minimum estimated chylomicron contribution to tissue DR was 63-280% higher than the maximum DR exposure from retinol-binding protein. Constant dietary intake may be important in maintaining VA concentrations in extrahepatic tissues.

Systemic levels of carotenoids from mangoes and papaya consumed in three forms (juice, fresh and dry slice).

BACKGROUND: Vitamin A deficiency is a public health problem in Cameroon. Data on the bioavailability of carotenoid in fruits currently consumed in Cameroon are scarce. OBJECTIVE: To assess the systemic levels of carotenoids from mangoes and papaya consumed as juice, fresh or dried slices. METHODS: Two groups of seven healthy volunteers (24 and 25 years of age; body mass index: 21 and 22 kg/m(2) respectively for subjects fed mango and papaya), were submitted to three types of meal treatments (juice, fresh and dried fruit). On the experiment day, meals served to fasting subjects during breakfast, included bread, yogurt and one of the three forms of fruit. All the treatments lasted only one day during which blood samples were collected three times; during fasting (T(0)), 4 h (T(4)) and 8 h (T(8)) after the test meal. The carotenoids and retinol contents were analysed by high-performance liquid chromatography method. RESULTS: From the major carotenoids present in papaya and mangoes, lutein, alpha-carotene and beta-carotene were found in considerable amounts. Lycopene and cryptoxanthin that were the major carotenoids in papaya samples appeared in low amounts in the chylomicrons. Significant correlations were observed between these carotenoids (at T(0), T(4) and T(8)). The three forms of consumption contributed to the rise of serum retinol levels. A comparison between the three forms revealed that papaya and mangoes consumed in form of juice or fresh fruit are the best forms because they had higher bioavailability values. CONCLUSION: Association of these different forms of consumptions could lead to a better availability of these fruits throughout the year and therefore efficiently contribute to improve vitamin A status of the population.

Apolipoprotein E enrichment of immuno-separated chylomicron and chylomicron remnants following saturated fatty acids.

AIM: We examined the effect of meal fatty acids on lipid and apolipoprotein concentrations of very low density lipoprotein (VLDL) and chylomicron/chylomicron remnants in lipid fractions with a Svedberg flotation rate (Sf) 60-400 and Sf 20-60. METHODS AND RESULTS: Six healthy middle-aged men received in random order mixed meals enriched with saturated (SFA), polyunsaturated (PUFA) or monounsaturated (MUFA) fatty acids on 3 occasions. VLDL and chylomicron/chylomicron remnants in the lipid fractions were separated by immunoaffinity chromatography against apo B-100. In the Sf 60-400 chylomicron/chylomicron remnants, triacylglycerol and cholesterol concentrations were significantly lower following PUFA compared with SFA and MUFA (P < or = 0.05). Apolipoprotein (apo) E responses were significantly higher after SFA in chylomicron/chylomicron remnants and VLDL compared with PUFA and MUFA (P < 0.007). However, apo B responses (particle number) were higher following MUFA than SFA (P = 0.039 for chylomicron/chylomicron remnants). Composition of the chylomicron/chylomicron remnants (expressed per particle) revealed differences in their triacylglycerol and apo E contents; in the Sf 60-400 fraction, SFA-rich chylomicron/chylomicron remnants contained significantly more triacylglycerol than MUFA (P = 0.028), more apo E than PUFA- and MUFA-rich particles (P < 0.05) and in the Sf 20-60 fraction, more apo E than MUFA (P = 0.009). CONCLUSION: There are specific differences in the composition of chylomicron/chylomicron remnants formed after saturated compared with unsaturated fatty acid-rich meals which could determine their metabolic fate in the circulation and subsequent atherogenicity.

Metabolic dysregulation in diabetes and HIV-associated insulin resistance: from fatty acids to fat distribution

Insulin resistance is one of the most important aspects of the metabolic dysregulation in diabetes and the metabolic syndrome. While most experts agree on the disturbed glucose-insulin axis in insulin resistance, the effects on lipid metabolism have received much less attention. Generally, fasting plasma triglycerides are slightly elevated and HDL cholesterol is diminished in the insulin resistance syndromes. Especially, the postprandial state seems to be one of the most important phases in which all the metabolic dysregulations come together. Postprandial lipemia itself is one of the causes of insulin resistance, and since postprandial lipemia is exaggerated in these syndromes, postprandial studies may be the best situation to investigate insulin resistance. Furthermore, postprandial hyperlipidemia has been closely linked to atherosclerosis making this the major risk factor in insulin resistance. One of the less well studied aspects of postprandial lipemia, which is closely related to insulin resistance, is peripheral fatty acid trapping and adipose tissue distribution. In HIV lipodystrophy, aberrant adipose tissue deposition and impaired peripheral fatty acid trapping are important determinants of many of the metabolic disturbances seen in this disorder. Therefore, HIV lipodystrophy is an interesting model to elucidate the molecular mechanisms regulating fatty acid trapping and adipose tissue distribution. Recent studies have clearly shown that components of the complement system play an important role in lipoprotein metabolism and fatty acid regulation. Especial attention has been drawn to the complement component 3 (C3) which is also a strong predictor of the metabolic syndrome. C3 is synthesized by adipose tissue during lipolysis of triglyceride rich lipoproteins. This process seems to be disturbed in different situations of insulin resistance like the metabolic syndrome, type 2 diabetes and familial combined hyperlipidemia. C3 may be a potential link between inflammation and lipoprotein dysmetabolism. Surprisingly, C3 concentrations are also modulated by several interventions designed to treat the me metabolic syndrome, like statins. Other inflammatory markers like leukocyte count and activation behave similar to C3 concentrations, especially during the postprandial phase. In this overview we will discuss several metabolic aspects of two examples of the insulin resistance syndrome, type 2 diabetes and HIV lipodystrophy

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Triacylglycerol oxidation in pig lipoproteins after a diet rich in oxidized sunflower seed oil.

The effects of two sunflower seed oil diets differing in oxidation levels (PV in oils 1 and 190 mequiv O2/kg) on lipoprotein TAG and total lipid oxidation were investigated in growing pigs. For 2 wk, two groups of 10 pigs were fed either of the diets, after which blood samples were collected. A method based on RP-HPLC and electrospray ionization-MS was used for the analysis of oxidized TAG molecules in chylomicrons and VLDL. The baseline diene conjugation method was used for the estimation of in vivo levels of lipoprotein lipid oxidation. TAG molecules with a hydroxy, an epoxy, or a keto group attached to a FA, as well as TAG core aldehydes were detected in the samples. Typically, lipoprotein TAG and total lipids were more oxidized in the pigs fed on the oxidized oil compared with those fed on nonoxidized oil. Oxidation of dietary fat was thus reflected in the lipoprotein oxidation, which confirmed our earlier findings.

Hyperlipidaemic effect of fish oil in Bio F1B hamsters.

We investigated the dietary influence of low and high levels of fish oil, supplemented with or without dietary cholesterol, on the plasma lipoprotein profile in Bio F1B hamsters, a model susceptible to diet-induced hyperlipidaemia. The MIX diet, a diet supplemented with a mixture of lard and safflower-seed oil, was used as the control diet to maintain the saturated MUFA and PUFA levels similar to the fish-oil diet. The animals were fed the specific diets for 2 weeks and fasted for 14 h before killing. The plasma from the animals fed high levels of fish oil was milky and rich in chylomicron-like particles. The plasma total cholesterol, VLDL- and LDL-cholesterol and -triacylglycerol concentrations were significantly higher, whereas HDL-cholesterol was lower in hamsters fed fish oil compared with the MIX-diet-fed hamsters. Increasing the amount of fat in the diet increased plasma lipids in both the fish-oil- and the MIX-diet-fed hamsters; however, this hyperlipidaemic effect of dietary fat level was greater in the hamsters fed the fish-oil diet. The hepatic lipid concentrations were not dramatically different between the fish-oil-fed and the MIX-diet-fed hamsters. However, the hepatic LDL-receptor mRNA levels were significantly low in the fish-oil-fed hamsters compared with the MIX-diet-fed hamsters. Increasing the amount of fish oil in the diet further decreased the hepatic LDL-receptor mRNA expression. It is concluded that F1B hamsters are susceptible to fish-oil-induced hyperlipidaemia, especially at high fat levels, and this increase is partially explained by the inhibition of hepatic LDL-receptor mRNA expression.

Avaliação da função endotelial e da cinética de quilomícrons em homens saudáveis com redução isolada do HDL-Colesterol: efeitos da niacina / Endothelial function and chylomicron-like kinetics assessment in helthy men with isolated low HDL-cholesterol: niacin's effect

Cerca de 35 per cent dos coronariopatas não têm fatores de risco convencionais. Estudamos o HDL-C baixo e sua relação com a função endotelial utilizando ultra-som de alta resolução para avaliação da dilatação mediada por fluxo (DMF) da a. braquial e o clearence de quilomícrons artificiais(CQA). / Almost 35 per cen of CAD patients do not have conventional risk factors. We have studied the low HDL-C and its relationship with the endothelial function using high resolution ultra-sound to evaluate the flow-mediated dilation (FMD) of the brachial artery and the chylomicron-like emulsion clearence...

Chylomicron remnant concentrations in patients with coronary artery disease.

Persisting chylomicron remnants have been linked to premature atherosclerosis. The analysis of chylomicron remnant concentrations by an oral triglyceride tolerance test, however, is time-consuming for the study subjects and requires large resources in the laboratory. Therefore, only small numbers of subjects have been studied in the past. The aim of this study was to elucidate the prevalence of elevated chylomicron remnants, to identify effectors of chylomicron remnant clearance and to compare chylomicron remnants in the prediction of coronary artery disease with other risk factors. We applied a novel oral triglyceride tolerance test to 423 patients (368 males, 55 females) with a confirmed diagnosis of coronary artery disease (CAD) and to 390 control subjects (295 males, 95 females) in a case-control setting. This study revealed that elevated chylomicron remnant concentrations (retinyl esters > 1.5 micromol/l) are present in 20% of all subjects. Male gender, the apolipoprotein E2 isoform, and higher body mass index were associated with increased chylomicron remnant concentrations. However, chylomicron remnants were lower and plasma triglycerides higher in patients with CAD. We conclude that screening for a delayed clearance of chylomicron remnants is of little clinical value in CAD.

Influence of triacylglycerol structure on the postprandial response of factor VII to stearic acid-rich fats.

BACKGROUND: The consumption of a synthetic, randomized, stearic acid-rich triacylglycerol results in decreased postprandial lipemia and activated factor VII (FVII:a) compared with cocoa butter (a nonrandomized, symmetrical, stearic acid-rich triacylglycerol). It was hypothesized that this difference is a consequence of the differences in structure between the 2 triacylglycerols. OBJECTIVE: The objective was to test whether the consumption of randomized cocoa butter decreases postprandial lipemia and FVII:a. DESIGN: A randomized crossover trial with 17 male subjects compared the effects of meals containing 50 g fat provided as a symmetrical (cocoa butter) or an asymmetrical (randomized cocoa butter) triacylglycerol on postprandial changes in lipids, chylomicron composition, and FVII:a. RESULTS: After randomization, the postprandial area under the curve for plasma triacylglycerol decreased by 41% (P < 0.01). At 3 h the plasma concentrations of triacylglycerol, palmitic acid, stearic acid, and oleic acid were 26%, 18%, 34%, and 19% lower, respectively. The proportion of oleic acid in the sn-2 position of the chylomicron triacylglycerol was reduced from 67.4 mol% to 35.9 mol% and resulted in an increase in the proportion of stearic acid in the sn-2 position from 9.2 mol% to 25.4 mol%. FVII:a did not increase 6 h after consumption of the randomized cocoa butter (: 1.2; 95% CI: -2.7, 4.6 U/L) but increased significantly (: 7.7; 95% CI: 2.5,12.9 U/L) 6 h after consumption of the unrandomized cocoa butter. CONCLUSIONS: Symmetrical stearic acid-rich triacylglycerol with oleic acid in the sn-2 position appears to be absorbed more rapidly than is asymmetrical triacylglycerols with long-chain saturated fatty acids in the sn-2 position, which leads to activation of FVII.