Biomedical subjects

G Lepage

Publications and source records attributed to G Lepage.

At least 55 records · Page 3Linked to original sources

PubMed1989

Total parenteral nutrition in the newborn: energy substrates and plasma total fatty acids.

Carbohydrate and lipid intakes have both been found to modulate the metabolism of long-chain fatty acids. To define the respective influence of these two energy substrates on plasma fatty acid concentrations, 32 studies were performed in 16 parenterally fed newborn infants (mean +/- SEM, birth wt: 2.15 +/- 0.1 kg, age: 10 +/- 1 d). In a paired cross-over design, the infants received for a given level of energy (60 versus 80 kcal/kg/d) two 6-d isonitrogenous and isocaloric regimens constructed so that the level of fat intake, 1 or 3 g/kg/d varied inversely with that of glucose. Total plasma fatty acid levels did not reflect the composition of the emulsion and varied with energy substrates. Plasma levels of three fatty acids rose inversely to the lipid intake, during the high glucose regimen: 16:1w7, 20:3w9 biologic markers of essential fatty acid deficiency, and 20:3w6 a derivative of 18:2w6. Glucose intake could exert its influence on 20:3w9 and 20:3w6 via insulin, an activator of delta 6 desaturase. Both glucose and fat should be taken into account when evaluating plasma fatty acid profile.

Energy Intake↗

PubMed1989

Direct transesterification of plasma fatty acids for the diagnosis of essential fatty acid deficiency in cystic fibrosis.

This study was aimed at redefining criteria for essential fatty acid (EFA) deficiency with the use of the direct transesterification procedure (1986. J. Lipid Res. 27: 114-120) and at determining whether a simple assay of total fatty acids (FA) is as predictive of EFA deficiency as the FA pattern from plasma, red cell, and platelet phospholipids. Fasting blood samples were taken from 163 cystic fibrosis (CF) patients who were encouraged to consume 35-40% of their calories as fat. Their mean (+/- SD) age was 9.6 +/- 4.8 yr. The control group consisted of 44 unaffected siblings aged 13.1 +/- 3.1 yr. The 20:3(n-9)/20:4(n-6) ratio in 77 (47%) CF children was more than 2 SD above the values (mean +/- SD) of 0.021 +/- 0.007 obtained in the 44 controls. Groups of EFA-sufficient (n = 10) and EFA-deficient (n = 7) subjects were selected for further studies. The plasma total FA 20:3(n-9)/20:4(n-6) ratios of 0.029 +/- 0.003 in EFA-sufficient and of 0.216 +/- 0.103 in EFA-deficient was as good a discriminant as FA in phospholipids from plasma, red cell PC, and platelets. Among the 21 individual fatty acids, 20:3(n-9), which was also found in controls, and 16:1(n-7) (palmitoleic) proved to be the most sensitive indices of EFA deficiency. They are equally reliable in plasma, red cells, and platelets, but the inverse linear relationship (r = -0.91) between the n-7 family and 18:2(n-6) proved to be more closely associated with EFA deficiency than the one (r = 0.66) between 20:3(n-9) and 20:4(n-6).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1989

Relationship of decreased hepatic lipase activity and lipoprotein abnormalities to essential fatty acid deficiency in cystic fibrosis patients.

Polyunsaturated fatty acids are known to affect plasma lipids and lipoproteins but there is no information on the effect of essential fatty acid (EFA) deficiency on lipoprotein composition. The purpose of this study was to characterize lipoproteins from 17 cystic fibrosis (CF) patients in relationship to their EFA status (eicosatrienoic/arachidonic acid ratio) and compare them with those of 10 healthy siblings (SIB) and of 10 unrelated controls. In 7 EFA-deficient (EFAD) and 10 EFA-sufficient (EFAS) patients, hypocholesterolemia was associated with a decrease of HDL-cholesterol and of LDL-cholesterol which was more marked in the EFAD group. Similarly, although triglyceride enrichment of VLDL, LDL, HDL2, and HDL3 with a concomitant reduction of cholesteryl esters from all particles except HDL2 was observed in both CF groups, it was more sizable in the EFAD patients. These changes led to an increase in the particle size of VLDL, LDL, and HDL2 whereas the distribution of HDL3 was skewed to smaller particles. Alterations in the apoprotein composition of particles were greater in EFAD than in EFAS. A decrease of total postheparin lipolytic activity was observed in the two groups of CF patients as well as in siblings. It was entirely accounted for by hepatic lipase (mumol FFA/ml per h) which was more severely diminished in EFAD (2.8 +/- 0.6) than in EFAS (4.4 +/- 0.7) and SIB (5.1 +/- 0.5). Although the two groups of CF children differed in terms of growth, severity of malabsorption, and vitamin E status, these data suggest that disturbance of lipoprotein concentration, composition, size, and metabolism (hepatic lipase) may be in part related to EFA deficiency. Further studies are necessary to explore the effect of EFA deficiency on hepatic lipase activity.

Adolescent↗

PubMed1988

Lipid abnormalities in pancreatic tissue of streptozotocin-induced diabetic rats.

Pancreatic lipid and fatty acid composition was determined in streptozotocin-induced diabetic rats and compared to control and insulin-treated diabetic rats. A pronounced decrease of total fatty acids was recorded and mainly accounted for by a drop of fatty acids in glycerides. Cholesterol, on the other hand, was significantly increased two- to three-fold, leading to an elevated cholesterol/phospholipid ratio. Morpho-cytochemical studies confirmed these findings because the multiple lipid droplets present in acinar cells of diabetic animals were found to be of cholesterol nature. The major alterations in phospholipid-fatty acid composition were characterized by an increase of linoleate coupled to a decrease of monounsaturates and arachidonate, suggesting defective metabolism of saturates and of linoleate. This was further supported by fatty acid ratios that suggested low delta 5 and delta 9 desaturation. Daily administration of insulin for 10 days restored and overcorrected the various lipid alterations. This study suggests that there are alterations in lipid composition and metabolism in the exocrine pancreas of chronic streptozotocin-induced diabetic rats. Their possible role in the mechanism regulating pancreatic function and secretion remains to be elucidated.

Animals↗

PubMed1988

Digestive and absorptive phase anomalies associated with the exocrine pancreatic insufficiency of cystic fibrosis.

The pancreas has an enormous reserve capacity, and significant malabsorption usually signals complete absence of exocrine function. However, there is evidence that acid lipases of nonpancreatic origin play an important compensatory role. Complete duodenal hydrolysis of fat requires a series of complex interdependent physicochemical events involving pancreatic lipase, colipase, phospholipase A2, and bile salts in an environment where the pH must be close to neutrality. Lipolytic products must then be shuttled through the unstirred water layer to the surface of the microvillus membrane by ionized bile salts, which must be present in sufficient concentrations to form micelles. In pancreatic insufficiency, there is not only a defective lipolytic phase but also an impaired micellar phase. The output of bile salts is decreased because of increased fecal loss. Furthermore, a significant percentage of bile salts precipitate because the duodenum is acidic and there is a large predominance of glycine conjugates. Although much less work has been done on the absorptive phase of patients with pancreatic insufficiency, there is tentative evidence that defective phospholipid absorption, essential fatty acid deficiency, and protein malnutrition could impair the absorptive phase, particularly chylomicron formation. Although significant advances have been made in our understanding of factors responsible for malabsorption associated with pancreatic insufficiency, much remains to be done for the further delineation of defects. It is hoped that this will lead to further refinements of enzyme preparations and to new strategies of intervention.

Cystic Fibrosis↗

PubMed1988

The influence of taurine on the bile acid maximum secretory rate in the guinea pig.

In view of the effect of taurine feeding on the cholestasis induced by sulfated lithocholate in the guinea pig, it was of interest to explore the influence of taurine on the bile acid secretory maximum (SRm) of chenodeoxycholic acid and of its glycine and taurine conjugates. Bile acid secretory rate measured in response to stepwise increasing rates showed for chenodeoxcholic acid an SRm of 147 +/- 6 nmol/min/g liver and any SRm that was higher (p less than 0.01) for taurine than for glycine (426 +/- 21 versus 327 +/- 24 nmol/min/g liver). Pretreatment for 3 days with taurine 0.5% in drinking water led to a 70% increase of the SRm for chenodeoxycholic acid. Analysis of the biliary bile acids after supplemental taurine demonstrated a large increment of tauroconjugates and no change in the percent of free bile acids or of sulfated forms. Experiments with labeled chenodeoxycholic acid showed no difference in the distribution of radioactivity between total liver, blood, bile, and urine on and off taurine thereby suggesting that neither sinusoidal uptake nor translocation across the cell were factors responsible for the difference in SRm. Inasmuch as taurine feeding increased the SRm for glycine by 30% and for taurine by 25%, it is suggested that taurine augments the canalicular excretion of bile acids that represents the rate-limiting step in the transfer of bile acids from blood into bile through a mechanism that cannot be explained only by a modification of the conjugation pattern.

Animals↗

PubMed1988

Circulating lipids and lipoproteins in glycogen storage disease type I with nocturnal intragastric feeding.

With the advent of nocturnal intragastric feeding which protects against acute metabolic complications and promotes growth, patients with glycogen storage disease type I are attracting less attention. However, several biochemical alterations persist and suggest that the long-term risk of atherosclerotic heart disease remains high. Persisting hypertriglyceridemia and hypercholesterolemia were found in seven glycogen storage disease type I subjects, six of them following 5-6 yr of nocturnal intragastric feeding. When compared to ten age-matched controls, the patients showed significantly (P less than 0.001) higher low density lipoprotein cholesterol (LDL-C) (247.7 +/- 46.8 vs. 115.3 +/- 5.0 mg/dl) and lower high density lipoprotein cholesterol (HDL-C) (26.4 +/- 3.4 vs. 55.8 +/- 2.9 mg/dl). Triglyceride (TG) enrichment with cholesteryl ester depletion characterized the lipoprotein classes. The diameters of very low density lipoproteins (VLDL) and LDL were larger, while that of HDL was smaller and consistent with the predominance of the HDL3 subclass and a lower apoA-I/apoA-II ratio. The raised levels of TG appeared attributable not only to the well-described lipogenesis, but also to impaired catabolism of fat, as evidenced by the significantly (P less than 0.001) decreased activity of both peripheral lipoprotein lipase (3.17 +/- 0.43 vs. 14.15 +/- 0.50 mumol FFA.ml-1.hr-1) and hepatic lipase (1.88 +/- 0.30 vs. 4.83 +/- 0.90). This may well explain the high concentration of intermediate density lipoprotein (IDL) and the impaired conversion of HDL3 to HDL2. Low apoC-II/apoC-III1 could be related to defective lipoprotein lipase activity. These data suggest that glycogen storage disease type I patients on nocturnal intragastric feeding remain at risk for atherosclerosis and its complications.

Adolescent↗

PubMed1988

Specific methylation of plasma nonesterified fatty acids in a one-step reaction.

Analysis of plasma nonesterified fatty acids (NEFA) by gas-liquid chromatography requires procedures that are both lengthy and cumbersome. A 45-min direct methylation procedure was carried out at 24-29 degrees C on 150 microliter of plasma added with an internal standard in 5.0 ml of methanol-acetyl chloride 50:1 (v/v). To stop the reaction, 3 ml of 6.0% K2CO3 was added. After addition of 150 microliter of hexane, shaking and centrifugation, an aliquot of the upper phase was injected into the gas chromatograph. The specificity of the methylation reaction for NEFA without hydrolysis of other classes of plasma lipids was substantiated with appropriate standards. This one-step specific methylation procedure is superior to currently used methods.

Chromatography, Gas↗

PubMed1987

Plasma and lipoprotein fatty acid composition in glycogen storage disease type I.

Nocturnal intragastric feeding has been shown to be an effective means to improve clinical and biochemical features in glycogen storage disease type I (GSD-I). In this study, we investigated the fatty acid patterns in a whole plasma and in circulating lipoproteins in patients on this therapy. The results demonstrated massive concentration of total fatty acids coupled with higher levels of triglycerides, free cholesterol, cholesterol ester and phospholipids. This hyperlipidemia involved all fatty acids without distinction of carbon or bond numbers. However, the increase was more pronounced for saturated than polyunsaturated fatty acids, as was demonstrated by the ratios of both oleic acid to linoleic acid (1.91 +/- 0.40 vs 0.80 +/- 0.09 in controls) and of omega 3 + omega 6 to omega 9 fatty acid families (0.92 +/- 0.11 vs 1.66 +/- 0.08 in controls). The fatty acid patterns in very low (VLDL), low (LDL) and high (HDL) density lipoprotein showed substantial differences in composition, reflecting an association between an abnormal lipoprotein pattern and essential fatty acid deficiency. Furthermore, GSD-I patients exhibited a significant increase in VLDL (17 +/- 2 vs 47 +/- 7 mg/dl) and LDL cholesterol (124 +/- 7 vs 206 +/- 24 mg/dl), coupled with a decrease in HDL cholesterol (49 +/- 4 vs 28 +/- 3 mg/dl). These data documenting high LDL cholesterol and low HDL cholesterol associated with an increased concentration and proportion of saturated fatty acids suggest that GSD-I patients on nocturnal intragastric feeding are at high risk for atherosclerosis and its complications.

Adolescent↗

PubMed1987

Storage of medium-chain triglycerides in adipose tissue of orally fed infants.

The effect of the fatty acid content of the diet on that of adipose tissue was studied in 5 newborn infants studied prior to feeding and 30 infants fed ad libitum from birth with either human milk or a commercial formula as the sole nutrient. Significant positive linear correlations of dietary intake on adipose tissue content of fatty acids were found for both long- and medium-chain fatty acids (MCFA). Infants stored up to 12% of MCFAs in their subcutaneous fat. The technique of direct transesterification improved the recovery of the volatile MCFAs and could explain the finding that medium-chain triglyceride storage in adipose tissue is more extensive than in previous reports. This study documents that MCFAs are not used solely as a source of energy: they can be reesterified or serve for chain elongation, before being deposited in fat stores.

Adipose Tissue↗

PubMed1987

Taurine supplementation of a premature formula improves fat absorption in preterm infants.

The predominance of taurine (Tau) conjugated over glycine conjugated bile acids in infants fed human milk as opposed to those on formulas without added Tau could account for a more complete absorption of fat. Fifteen low birth weight infants were randomized to either Enfamil Premature or to Enfamil Premature added with 40 mumol/dl of Tau and compared to a third group made up of nine low birth weight infants fed their own mother's preterm milk. Formulas and human milk were fed according to tolerance and constituted the sole nutrition for 3 months. A metabolic study was carried out at 3 wk of age and control of growth was done periodically. Urinary Tau excretion (mumol/dl) was very low (p less than 0.001) in the group fed Enfamil Premature (0.3 +/- 0.1) when compared to the values obtained in infants supplemented with Tau (51.6 +/- 12.5) and in those on human milk (36.3 +/- 7.9). Infants supplemented with Tau (92.5 +/- 1.2) had a coefficient of fat absorption which was higher (p less than 0.05) than the unsupplemented group (87.5 +/- 7.9) and comparable to the human milk-fed group (91.6 +/- 1.4). The effect was more pronounced on the saturated fatty acids and varied inversely with their individual water solubility. There was no effect of Tau on nitrogen retention and growth was identical in the three groups. These data show that the addition of Tau to formula had no effect on growth but improved the absorption of fat especially saturated fatty acids which require higher concentrations of bile acids to form mixed micelles.

Absorption↗

PubMed1987

Intestinal apoB synthesis, lipids, and lipoproteins in chylomicron retention disease.

Chylomicron retention disease is characterized by fat malabsorption, hypocholesterolemia, normal fasting triglycerides, and marked intestinal steatosis despite the presence of both plasma and intestinal apoprotein B. The defect remains unknown but presumably involves the synthesis or secretion of chylomicrons. The present investigation examines this hypothesis by studying the biosynthesis of chylomicrons in cultured jejunal explants and by defining the quantitative and qualitative abnormalities of plasma lipids and of circulating lipoproteins. Following 2-3 years of a low fat diet supplemented with medium chain triglycerides, six patients with chylomicron retention disease had significantly higher triglyceride (TG) levels coupled with a decrease in both free (FC) and esterified cholesterol (EC) as well as in essential fatty acids and phospholipids (PL) when compared to healthy controls. The low total plasma cholesterol was largely accounted for by low levels of both low density (LDL) and high density lipoprotein (HDL) cholesterol. VLDL and LDL were characterized by a diminished percentage of CE with an increase of TG while HDL contained relatively more FC as well as PL and less CE. The diameter of VLDL was larger whereas those of LDL and HDL were smaller than in normal controls. Jejunal explants, when incubated with [14C]palmitate, were capable of normal biosynthesis of TG, diglycerides, PL, and CE. These lipids, however, except for PL, were retained in the tissue and could not be secreted into the culture medium. Incubation of intestinal biopsies with [3H]leucine and [14C]mannose resulted in normal protein synthesis and reduced glycosylation. The presence of intestinal apoB-48 was confirmed by immunoblot using 2D8 antibodies. These data suggest that the intestinal defect in this disease results from a disorder of the final assembly of chylomicrons or in the mechanism of their exocytosis.

Apolipoproteins B↗

PubMed1987

Taurine improves the absorption of a fat meal in patients with cystic fibrosis.

The effect of taurine supplementation on the absorption of a fat meal was evaluated in patients with cystic fibrosis. In a cross-over design study, five patients with cystic fibrosis (12.1 +/- 2.6 years of age) and three control subjects received either placebo or taurine (30 mg/kg/d) for two 1-week periods, a month apart, followed by a fat meal test. Blood samples were drawn 0, 1, 2, 3, 5, 8 hours after the meal. Four patients with cystic fibrosis and severe steatorrhea despite appropriate enzyme therapy showed a significant (P less than .05) improvement in the absorption of triglycerides, total fatty acids, and linoleic acid while receiving taurine supplements. Three control subjects and one child with cystic fibrosis and mild steatorrhea receiving enzyme therapy did not experience such an effect. The difference in triglyceride absorption, when calculated as the area under the curve, receiving and not receiving taurine was significantly (P less than .05) correlated with the degree of steatorrhea. Furthermore, in contrast to control subjects, the fatty acid composition of chylomicrons in these four study patients showed important discrepancies with that of the fat meal and was corrected, in part, by taurine supplementation. These results suggest that taurine supplementation could be a useful adjunct in the management of patients with cystic fibrosis with ongoing fat malabsorption and essential fatty acid deficiency.

Adult↗

PubMed1986

Effect of dietary fat and residues on fecal loss of sterols and on their microbial degradation in cystic fibrosis.

Although various etiologic factors have been implicated, the mechanism responsible for bile acid malabsorption in CF remains unknown. Eight CF children studied twice on a normal diet supplemented with pancreatic enzymes and once during a one-month period of Vivonex administered by continuous nasogastric infusion were compared to age-matched controls. On the fat and residue-free elemental diet, there was a modest decrease in steatorrhea and no change in the daily excretion of nitrogen and neutral sterols. However, normalization of bile acid output (485.6 +/- 65.0 to 160.6 +/- 29.2 mg/24 hr) to control levels (150.2 +/- 60.7) was noted. Diminished microbial degradation of both neutral and acidic sterols and a smaller amount of bile acids adsorbed to decreased residues were also found. The data do not support the possibility of a bile acid ileal transport defect and suggest that the most important single factor responsible for the intraluminal sequestration of bile acids in CF is dietary residues. Because of significant ongoing losses of nitrogen and lipids, pancreatic enzymes should be given to CF patients on elemental diets.

Bile Acids and Salts↗

PubMed1986

Direct transesterification of all classes of lipids in a one-step reaction.

Conventional techniques for the determination of fatty acid composition of lipids require solvent extraction, purification, hydrolysis, and derivatization procedures that are both lengthy and cumbersome. A 1-hr direct transesterification procedure carried out in methanol-benzene 4:1 with acetyl chloride circumvented all these steps and was applicable for analysis of both simple (triglycerides) and complex lipids (cholesteryl esters, phospholipids, and sphingomyelin). Recoveries (greater than 95%) of standards unaffected by the presence of 5% water and 200 mg of silica suggested that the technique could be used for the quantitative analysis of total fatty acids as well as of fatty acids in classes of lipids separated on silica from biological samples. When compared to the Folch procedure, the technique led to a 20.1% increase in total fatty acids for plasma, 3.9% for feces, 7.4% for bile, and 9.7% for rat liver. We therefore conclude that this one-step direct transesterification procedure is superior to currently used methods, not only because of its simplicity and speed, but also because of its added precision.

Chemical Phenomena↗

PubMed1985

Protein quality and quantity in preterm infants receiving the same energy intake.

Fifteen low-birth-weight appropriate for gestational age infants, weighing 1.3 to 1.6 kg, were assigned to three isocaloric formulas differing in the quantity and form of nitrogen delivered. A balance study was done between 21 and 30 days after birth. Nitrogen retention expressed as milligram per kilogram per 100 kcal of metabolizable energy was greater with the 60:40 whey/casein and with the casein hydrolysate preparations than with the 20:80 whey/casein formula, which provided the same amount of energy (150 kcal/kg/day) but smaller quantities of protein (3.5 g/kg/day) than the two others (4.3 g/kg/day and 4.4 g/kg/day). Weight gain until discharge from the hospital and increment of height and head circumference over a three-month period showed an advantage of the two formulas providing higher intakes of protein. This study suggests that with high-energy intakes, protein quality does not affect nitrogen retention and growth unless the quantity of protein ingested falls below a critical level.

Caseins↗

PubMed1985

Effect of taurine supplements on fat absorption in cystic fibrosis.

Patients with cystic fibrosis have an increased proportion of glycine conjugated bile acids with diminished tauroconjugates which could contribute to fat malabsorption. Twenty-two CF children with documented steatorrhea were supplemented with taurine capsules (30 mg/kg/day) and placebo during separate 6-month treatment periods. Alteration of the glycine/taurine conjugation pattern was verified in two patients who showed a predominance of tauroconjugates as a result of taurine supplementation. On taurine, steatorrhea was reduced (p less than 0.05) by 17.6 +/- 9.7% in 19 patients who completed the study as was the excretion of long-chain saturated fatty acids. There was no change in linoleic acid (C 18:2) excretion. In the 10 patients with a more severe degree of steatorrhea the decrease in fat loss approached 20% and a close relationship was found (r = 0.84, p less than 0.01) between the extent of the fatty acid loss on placebo and the decrease of this loss on taurine. A linear relationship was found between the percentage decrease of individual fatty acids and their log solubility in water. No change was found in the daily excretion of bile acids, neutral sterols, and nitrogen. Fasting plasma fatty acids, cholesterol, and triglycerides were also unchanged. Monitoring of growth over the two 6-month periods revealed a marginal (p less than 0.1) increase of weight velocity expressed as a percentage expected for age (83.4 +/- 11.3----117.1 +/- 16.5). The increase in height velocity in response to taurine showed a more modest trend (95.3 +/- 7.8----110.7 +/- 10.6).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1984

Improved recovery of fatty acid through direct transesterification without prior extraction or purification.

Methods currently in use for the quantitative measurement of fatty acids by gas-liquid chromatography after transesterification are usually lengthy and cumbersome. The technique described is a one-step reaction that is carried out in the same tube and bypasses all the extraction and purification steps. Recoveries of fatty acid and triglyceride standards (C6:0 to C24:1) were better than 96%. When the direct transesterification method was compared to the Folch extraction procedure, increases of fatty acid concentration of 11.4% and 15.8% were observed in human milk and adipose tissue, respectively. The method appears to be particularly advantageous for the recovery of the highly volatile medium chain triglycerides and there is no need to add an antioxidant to protect unsaturated lipids.

Adipose Tissue↗