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Effect of equimolar amounts of long-chain triglycerides and medium-chain triglycerides on plasma cholecystokinin and gallbladder contraction.

The present study was undertaken to compare the effects of equimolar amounts of long-chain triglycerides (LCT) and medium-chain triglycerides (MCT) on plasma cholecystokinin (CCK) concentrations and gallbladder contraction in man. On separate mornings and in random order six healthy volunteers ingested either 60 mmol LCT or 60 mmol MCT. Plasma CCK concentrations were measured by a sensitive and specific radioimmunoassay and gallbladder contraction by ultrasonography. Ingestion of LCT induced significant increases in plasma CCK from 2.8 +/- 0.5 to 6.5 +/- 0.7 pmol/l (p less than 0.005) and decreases in gallbladder volume from 33.4 +/- 5.9 to 13.2 +/- 4.2 cm3 (p less than 0.005). On the other hand, no significant changes in plasma CCK and gallbladder volume were found after MCT. Ingestion of MCT was followed by abdominal cramps and diarrhea, while LCT were without side effects. It is concluded that, in contrast to LCT, MCT do not induce CCK release and gallbladder contraction.

Adult↗

Influence of microsomal triglyceride transfer protein promoter polymorphism -493 GT on fasting plasma triglyceride values and interaction with treatment response to atorvastatin in subjects with heterozygous familial hypercholesterolaemia.

Familial hypercholesterolaemia (FH) is an autosomal dominant disease characterized by elevated levels of low-density lipoprotein-cholesterol (LDL-C). Phenotypic expression is highly variable, being influenced by diet, age, gender, body mass index, apolipoprotein E genotype and type of LDL-receptor gene mutation. Microsomal triglyceride (TG) transfer protein (MTP) is a protein involved in lipid metabolism. Polymorphism MTP -493 GT has been shown to modulate lipid levels in several populations. To analyse the effect of this polymorphism in the lipid phenotype expression of FH and treatment response, we studied a sample of 222 Spanish FH patients, of whom 147 were studied before and after treatment with 20 mg of atorvastatin daily during 6 weeks. The variant was analysed by polymerase chain reaction amplification and single-strand confirmation polymorphism. Treatment reduced LDL-C, total cholesterol and TGs. Baseline fasting TGs and very-low-density lipoprotein cholesterol levels were lower in female T allele carriers (TG: 111+/-51 mg/dl GG, 89+/-35 mg/dl GT, 83+/-26 mg/dl TT, P=0.022; very-low-density lipoprotein cholesterol: 24+/-13 mg/dl GG, 16+/-5 mg/dl GT, 17+/-5 mg/dl TT, P=0.018). Triglyceride response to atorvastatin was modulated by this polymorphism in men (P=0.009), but not in women, although differences between genotypes were maintained after treatment. In conclusion, the MTP -493 GT polymorphism modulates pre- and post-treatment plasma TG values of FH in Spanish subjects in a gender-specific way. Other environmental and genetic factors likely also modulate this response.

Alleles↗

Very low density lipoprotein triglyceride metabolism in relatives of hypertriglyceridemic probands. Evidence for genetic control of triglyceride removal.

The production and catabolism of very low density lipoprotein triglycerides (VLDL-TG) were determined in 11 index patients with primary hypertriglyceridemia and in their 70 first-degree relatives. In the probands the mean value for VLDL-TG production rate was twice normal, and the mean fractional catabolic rate (FCR) was reduced to 50% from normal. A similar kinetic pattern was also observed in most hypertriglyceridemic relatives. In the normotriglyceridemic relatives the mean values of both kinetic parameters were comparable to those of controls. No kinetic differences were observed between families with familial hypertriglyceridemia, familial combined hyperlipidemia, or genetically unclassified hypertriglyceridemia (all diagnosed by lipoprotein phenotypes). Thus, no explanation for the phenotypic differences between the two forms of familial hyperlipoproteinemia was found in plasma VLDL-TG metabolism. When the families were grouped according to the VLDL-TG production rate of the proband, there was no significant difference between the VLDL-TG production rates of relatives of "overproducer" probands and relatives of the probands with normal VLDL-TG production rate. In contrast, relatives of low FCR probands had significantly lower mean FCR than the relatives of probands with a normal FCR. This difference in FCR was present both in hypertriglyceridemic and normotriglyceridemic relatives. These results suggest that the catabolism (lipolysis) of VLDL-TG is under genetic control, whereas the VLDL-TG production rate is mainly related to obesity. It is likely that hypertriglyceridemia often develops on the basis of VLDL overproduction in individuals who have a genetically low VLDL triglyceride removal (lipolytic) capacity.

Adolescent↗

Effects of nonglucose substrates (xylitol, medium-chain triglycerides, long-chain triglycerides) and carnitine on nitrogen metabolism in stressed rats.

To evaluate the efficacy of nonglucose energy substrates in promoting nitrogen retention and survival in stressed states, two series of studies were done. In study 1, 50 rats underwent cecal ligation/perforation and subsequent infusion for 24 hr with one of four isocaloric (220 kcal/kg/day), isonitrogenous (1.4 g/N/kg/day), isovolemic regimens which differed in caloric source: Glucose (GLU) + long-chain triglycerides (LCT) (50%:50%), GLU + LCT + medium-chain triglycerides (MCT) (50%:32%:18%), GLU + LCT/Carnitine (10 mg/dl) or GLU + LCT + Xylitol (XYL) (33%:33%:33%). The nitrogen-sparing effect of GLU + LCT was not enhanced by the addition of carnitine to facilitate LCT mitochondrial uptake or by MCT to bypass carnitine-dependent transport. In contrast, relative to GLU + LCT GLU + LCT + XYL decreased urinary 3-methylhistidine (3MH) excretion (p less than 0.01), and enhanced nitrogen retention (p less than 0.01 vs GLU + LCT). For study 2, 24 male rats were anesthetized, cannulated for TPN, and given a 25% burn. They were then randomized into three dietary groups. The diets were isocaloric (103 kcal/kg/day) and isonitrogenous (2.0 g N/kg/day) but differed in nonprotein calorie source: GLU + LCT (51%:49%), GLU + Glycerol (51%:49%) and XYL + LCT (51%:49%). As in the septic animals, N balance was best with the xylitol regimen (p less than 0.01). The polyol, xylitol, appears to have a significant nitrogen sparing effect in stressed animals.

Animals↗

Lipid infusion with different triglyceride cores (long-chain vs medium-chain/long-chain triglycerides): effect on plasma lipids and bilirubin binding in premature infants.

The possible beneficial effects of infusing a lipid emulsion containing 50% by weight of medium-chain triglycerides (MCT) compared with a standard long-chain triglyceride (LCT) emulsion were studied in 18 premature neonates (gestational age less than 34 weeks) requiring parenteral nutrition. The infants were assigned in a double-blind manner to receive one of the two lipid emulsions over 17 hours a day as a supplemental regimen for total parenteral nutrition. A lipid load of 1 g/kg per day was initiated on the third day of life and was increased at the rate of 1 g/kg per day until a maximal dose of 3 g/kg per day was obtained on the fifth day of life and maintained thereafter. Both bound and unbound bilirubin decreased with both infusion regimens during the study period. Despite a marked increase in plasma free fatty acid levels (260% in the MCT/LCT group compared with 210% in the LCT group), the fraction of unbound (free) bilirubin was significantly lower in the MCT/LCT group (34% vs 13%). Free fatty acid levels, corrected to albumin, were positively correlated to the percentage of free bilirubin only for the LCT lipid infusion. The finding of a significant elevation of plasma cholesterol levels only in the MCT/LCT group is now under investigation. Use of the MCT-containing emulsion was not associated with a higher frequency of adverse effects than the commonly used LCT-containing emulsion.(ABSTRACT TRUNCATED AT 250 WORDS)

Bilirubin↗

Implitapide, a microsomal triglyceride transfer protein inhibitor, reduces progression of atherosclerosis in apolipoprotein E knockout mice fed a Western-type diet: involvement of the inhibition of postprandial triglyceride elevation.

Microsomal triglyceride transfer protein (MTP) is essential for the synthesis of both chylomicron in the intestine and very low-density lipoprotein in the liver. An MTP inhibitor, (2S)-2-cyclopentyl-2-[4-[(2,4-dimethyl-9H-pyrido[2,3-b]indol-9-yl)methyl]phenyl]-N-[(1S)-2-hydroxy-1-phenylethyl]ethanamide (implitapide), has been shown to suppress atherosclerosis in apolipoprotein E knockout (apoE KO) mice. To elucidate the antiatherosclerotic mechanisms of implitapide in the mice, we examined the effects on plasma lipid levels, triglyceride (TG) elevation after oral fat loading, and development of atherosclerosis in apoE KO mice fed a Western-type diet. Implitapide at a dosage of approximately 3.2 mg/kg/day significantly reduced both total cholesterol and TG levels during the 8-week treatment period. In addition, implitapide significantly inhibited the increase in plasma TG levels after oral olive oil loading tests conducted after 4 weeks of treatment. After the treatment, implitapide significantly suppressed the atherosclerotic lesion area by 83% compared with a control group. These results provide direct evidence that the antiatherosclerotic effects of implitapide in apoE KO mice are associated with the inhibition of postprandial TG elevation, in addition to the reduction of both plasma total cholesterol and TG levels.

Animals↗

Comparison of triglyceride concentration with lipemic index in disorders of triglyceride and glycerol metabolism.

BACKGROUND: In plasma, triglycerides (TG) are transported in lipoprotein particles (mainly chylomicrons, very low-density and low-density lipoprotein). Turbidimetry (bichromatically at 660 and 700 nm) allows measurement of the lipemic (L) index. We explored the use of this index, in combination with a TG assay, to detect errors due to non-fasting, to assess abnormalities in TG metabolism and to detect patients with glycerol kinase deficiency (GKD). METHODS: We collected 2441 patient samples. Normolipidemic (n=2347), type IV hyperlipidemic (n=80), postprandial samples (n=22) and serial dilutions of Intralipid with saline (n=6) were selected. One patient presenting with GKD was included, as well as two patients with type I and type V hyperlipoproteinemia, respectively. RESULTS: We introduced the use of the ratio between the logarithm of serum triglycerides and that of the L-index (TG/L ratio). CONCLUSION: Although the proposed TG/L-index ratio cannot be regarded as an alternative for the accurate diagnosis of lipid disorders, it provides additional information about TG-containing particles.

Glycerol Kinase↗

Utilization of medium-chain triglycerides by neonatal piglets: II. Effects of even- and odd-chain triglyceride consumption over the first 2 days of life on blood metabolites and urinary nitrogen excretion.

In two experiments, 144 neonatal pigs were force-fed 12 ml of triglyceride containing fatty acids of even (C8, C10) or odd (C7, C9) medium-chain length (even-MCT, odd-MCT, respectively) or long- (greater than or equal to C16) chain length (LCT). Pigs were individually caged for measurement of urinary N excretion and(or) blood metabolites over 24 h. In Exp. 1, pigs were force-fed immediately after birth and were not allowed to suckle. Supplementation with triglyceride decreased 24-h N excretion compared with control animals given 12 ml of water, suggesting decreased breakdown of body protein and improved energy status. Blood glucose increased over 24 h in all pigs (P less than .05), but more in pigs given MCT (1.38 mM) than in those given LCT (.61 mM) or in controls (.85 mM) and more in animals given even-MCT (1.87 mM) than in those given odd-MCT (1.14 mM). In Exp. 2, pigs were allowed to suckle and were force-fed at 6, 18 or 48 h of age. An apparent improvement in utilization of even-MCT was observed between 6 and 18 h, as evidenced by a twofold vs a sixfold increase in 3-OH-butyrate (BHBA) concentration 1 h after dosing and a twofold vs 12-fold increase in plasma fatty acid concentration. This was not seen in pigs given odd-MCT. The BHBA response with odd-MCT was approximately half that observed with even-MCT in pigs 18 and 48 h old, but not in pigs 6 h old. No change in BHBA concentration (P greater than .1) was observed in pigs after force-feeding LCT at either 6, 18 or 48 h of age. Collectively, these data suggest that MCT may be better utilized than LCT and that there may be a differences in the utilization of even-MCT vs odd-MCT, depending on the age of the neonate. This could be related to chain length effects on digestion and absorption because plasma decanoate concentration changed very little, even though it composed 25% of the even-MCT supplement.

3-Hydroxybutyric Acid↗

Plasma triglyceride turnover in 92 adult normolipaemic and 30 hypertriglyceridaemic subjects--the effect of age, synthesis rate and removal capacity on plasma triglyceride concentration.

Plasma triglyceride (TG) turnover measurements were carried out in 92 healthy normolipaemic and 30 hypertriglyceridaemic subjects. The analysis of the data revealed an age-dependence of the efficiency with which triglyceride particles were removed from the circulation, the elimination capacity being lower in older than in younger subjects. The population at large displayed heterogeneity with regard to maximal removal capacity, as already reported. Of the three groups into which the subjects were divided according to elimination capacity, those of lowest capacity were proportionately more numerous in the hypertriglyceridaemic than in the control series. This indicates that high synthesis rate and low elimination capacity are both involved in the development of hypertriglyceridaemia in man. The TG turnover test is thought to be useful in analyses concerning the heritability of mixed hyperlipidaemic states. A statistically significant decrease of plasma lipoprotein lipase with age was established using a matched series, thus confirming earlier observations and demonstrating that turnover tests and analyses of TG-removing enzymes are in good agreement.

Adolescent↗

Cloning and regulation of hamster microsomal triglyceride transfer protein. The regulation is independent from that of other hepatic and intestinal proteins which participate in the transport of fatty acids and triglycerides.

Microsomal triglyceride transfer protein (MTP) is a heterodimer consisting of protein disulfide isomerase and a unique large subunit. Recent studies showing that an absence of MTP is a cause of abetalipoproteinemia indicate that MTP is required for the assembly of very low density lipoproteins in the liver and chylomicrons in the intestine. In this study, complementary DNA encoding the large subunit of hamster MTP was cloned. The cDNA sequence was used to design a 50-base pair oligonucleotide probe for a solution hybridization assay to quantitate MTP large subunit mRNA levels in a study of MTP regulation in male Syrian Golden hamsters. In animals fed a low fat diet, MTP exhibited a proximal to distal gradient of expression in the intestine. MTP activity and large subunit mRNA levels in the liver were about 25 and 10% that found in the proximal intestine, respectively. To investigate the effect of diet on MTP, hamsters were maintained for 31 days on one of four diets: 1) control low fat, 2) high fat, 3) low fat, high sucrose, or 4) diet 1 followed by a 48-h fast. The high fat diet increased MTP large subunit mRNA levels in the liver and throughout the small and large intestine. A 55 and 126% increase was observed in the liver and intestine (duodenum and jejunum), respectively. A 40% increase of intestinal MTP protein mass was also observed. The high sucrose diet caused a significant 55% increase in hepatic MTP mRNA levels but did not significantly affect the intestinal mRNA levels. MTP mRNA levels were unchanged in response to fasting. A short term dietary study showed that intestinal MTP mRNA was up-regulated within 24 h after initiating a high fat diet. An acute hepatic response was not observed. The regulation of MTP mRNA levels by high fat diets was compared to that of the liver fatty acid binding protein (L-FABP) and apolipoprotein B (apoB). ApoB mRNA levels were not significantly affected by a high fat diet. Although L-FABP mRNA levels were increased in the liver and intestine, the onset of the changes did not parallel that of MTP. These results suggest that L-FABP, apoB, and MTP, three proteins which play important roles in the transport of fatty acids and triglyceride in the liver and intestine, are not coordinately regulated by diet in hamsters.

Amino Acid Sequence↗

Fasting triglyceride and the triglyceride-HDL cholesterol ratio are not markers of insulin resistance in African Americans.

BACKGROUND: The "lipid criteria" consist of a triglyceride (TG) level of 130 mg/dL (1.47 mmol/L) or greater and a ratio of TG to high-density lipoprotein cholesterol (HDL-C) of 3 or greater. In Caucasians, the lipid criteria predict insulin resistance in individuals with a body mass index (BMI) of 25 kg/m(2) or greater. Our goal was to determine whether TG levels or TG-HDL-C ratio predicted insulin resistance in African Americans with a BMI of 25 kg/m(2) or more. METHODS: Of 125 African Americans, the 98 with a BMI of 25 kg/m(2) or more participated. All subjects had frequently sampled intravenous glucose tolerance tests with insulin resistance determined by the insulin sensitivity index. Subjects were divided into the following tertiles by insulin sensitivity: 12.8 to 4.3, 4.2 to 2.3, and 2.2 to 0.2 mU/L per minute. Insulin resistance was defined as being in the third tertile. Across tertiles, the distribution of variables was compared by 1-way analysis of variance. Areas under the receiver operating characteristic curve were determined to identify variables that predicted insulin resistance. RESULTS: Fasting insulin level, BMI, and waist circumference increased across tertiles (all P<.01), but TG levels and TG-HDL-C ratio did not (all P>/=.3). The mean +/- SE areas under the curves for fasting insulin, BMI, and waist circumference were 0.85 +/- 0.04, 0.72 +/- 0.05, and 0.71 +/- 0.05, respectively. For TG level and TG-HDL-C ratio, the areas under the curves were 0.55 +/- 0.06 and 0.56 +/- 0.06, respectively, meaning that the true-positive rate was nearly equal to the false-positive rate. Therefore, they could not be used as markers of insulin resistance. Furthermore, 17 subjects met the lipid criteria but only 7 were in the insulin-resistant tertile, making the sensitivity of these criteria to identify insulin resistance only 17%. CONCLUSION: In African Americans, TG levels and TG-HDL-C ratio are not reliable markers of insulin resistance.

Adult↗

Cholesteryl ester analogs inhibit cholesteryl ester but not triglyceride transfer catalyzed by the plasma cholesteryl ester-triglyceride transfer protein.

A lipid transfer protein complex (LTC), purified from human plasma by immunoaffinity chromatography, catalyzed the interlipoprotein transfer of cholesteryl esters (CE) and triglycerides (TG). The CE transfer activity of LTC was governed by the structure of the CE. Incubation of LTC with long chain CE both activated and stabilized LTC. Short chain CE also enhanced the CE and TG transfer activity of LTC during the initial time of incubation. However, LTC's incubation with short chain CE induced a subsequent and time-dependent loss of CE transfer activity without concomitant loss of TG transfer activity. The data indicate that the CE and TG transfer activity of LTC can be regulated independently.

Binding Sites↗

Inhibition of hepatic triglyceride secretion and exogenous triglyceride clearance in the cholestatic rat.

Extrahepatic biliary obstruction in humans and rats leads to hypertriglyceridemia. The observed hypertriglyceridemia could result from either a defect of plasma triglyceride (TG) catabolism or hepatic over-production of TG. To examine these questions we have used the rat model to determine hepatic TG secretion by the Triton WR-1339 methodology (inhibition of peripheral lipolysis) and exogenous TG clearance (after i.v. injection of Intralipid). Four groups of rats were studied: group OB--48 h post-operative--bile-duct obstructed; group DV--bile diverted; group SC--sham-operated controls; and group FC--48 h fasted, unoperated controls. The hepatic TG secretion rate for group OB rats was a factor of 7 lower than that of either group SC or FC, and 5 times lower than that for group DV. There were no differences between the hepatic TG secretion rates of groups DV and FC or SC. After i.v. injection of Intralipid, plasma TG decreased with first-order kinetics. The rate constant was taken as the exogenous TG clearance rate (ETGCR). Mean ETGCR for group OB was a factor of 3 lower than that for either control group; while the ETGCR for group DV was equivalent to the control groups. Thus biliary diversion does not affect hepatic TG secretion or the ETGCR. The apparent cause of the hypertriglyceridemia of cholestasis in the bile-obstructed rat is impaired plasma TG catabolism.

Animals↗

Human plasma triglyceride labeling after high sucrose feeding. II. Study on triglyceride kinetics and postheparin lipolytic activity.

Kinetic studies of the very-low-density lipoprotein triglycerides (VLDL-TG) turnover by endogenous labeling with glycerol-2-3-H were performed in 13 patients in the postabsorptive state, first after 10-14 days on a low-sucrose high-starch diet, then again after 10-14 days of isocaloric high-sucrose low-starch diet (HSD). After HSD, a significant decrease in the fractional turnover rates of VLDL-TG was observed, as well as a modest but significant increase in its pool size, but the net turnover rates remained unchanged. Using Michaelis-Menten formulation, we have further calculated the Vmax and Km's of the removal system for VLDL-TG and found that the Vmax and Km's do not differ significantly between the two dietary periods. These results suggest that the removal mechanism for VLDL-TG has not changed after 10-14 days on the HSD, at least when the patients are studied in the postabsorptive state. Measurements of postheparin lipolytic acitivty under fed condition in 17 patients (including the 13 patients above) have shown a decrease after HSD. However, a defect in the removal of plasma-TG related to decreased activity of tissue-lipoprotein lipase in the fed state has not been conclusively uncovered by the kinetic studies performed in the postabsorptive state, and cannot contribute significantly to the expansion of VLDL-TG pool.

Adult↗

Effect of acute hyperglycemia on plasma triglyceride concentration and triglyceride secretion rate in non-fasted rats.

The effect of an intravenous infusion of glucose on plasma triglyceride (TG) concentration in fed rats was determined in order to partially elucidate the mechanism of diabetes-induced hypertriglyceridemia. Glucose infused at 8 mg/kg per min caused the plasma TG concentration to be elevated significantly when compared to controls infused with saline alone. In rats which were euglycemic (clamped, insulin infused at 2.5 mU/kg per min), plasma TG concentration remained constant throughout the glucose infusion period (8 mg/kg per min). Hyperglycemic rats infused with insulin (2.5 mU/kg per min) as well as with glucose (16 mg/kg per min) were also hypertriglyceridemic. Infusion of insulin alone did not change the concentration of plasma TG over a 150 min period. Glucose was also infused (8 mg/kg per min) with somatostatin (1 micrograms/kg per min) to block endogenous production of insulin. Somatostatin infusion did not suppress glucose-induced hypertriglyceridemia. For all treatments, the net change in TG concentration was found to positively correlate with the net change in plasma glucose concentration at 150 min after the infusions (r = 0.83, P less than 0.001). The higher TG concentration in the glucose infused, hyperglycemic clamp and glucose plus somatostatin groups reflected an increased rate of TG secretion, in the presence of a lower concentration of plasma free fatty acids. These results suggest that in a non-fasted state, acute hyperglycemia increases plasma TG by stimulating hepatic TG secretion, in a manner which is independent of either plasma insulin or free fatty acids levels.

Animals↗

Soy protein reduces triglyceride levels and triglyceride fatty acid fractional synthesis rate in hypercholesterolemic subjects.

To examine the effects of protein source and isoflavones on triglyceride (TG) fatty acid (TGFA) and cholesterol biosynthesis, subjects (>50 years, LDL cholesterol >130 mg/dl) underwent a four-phase randomized cross-over feeding trial. Diets contained either isolated soy protein or common sources of animal protein (25 g/1000 kcal), without or with isoflavones (49 mg/1000 kcal) and were each fed for 6 weeks. Blood samples from 20 hyperlipidemic subjects (6M, 14F, 62 +/- 9 years, BMI 26 +/- 3 kg/m(2), LDL cholesterol >160 mg/dl after feeding animal protein without isoflavones) were selected to measure TGFA fractional synthetic rate (TGFA-FSR) and free cholesterol fractional synthetic rate (FC-FSR) over 24h as deuterium oxide uptake into TGFA and free cholesterol. Soy protein reduced TG by 12.4% (P < 0.0001), total cholesterol by 4.4% (P < 0.001), and LDL cholesterol by 5.7% (P = 0.003) compared to animal protein. The TGFA-FSR was reduced by 13.3% (P = 0.018) and FC-FSR was increased by 7.6% (P = 0.017) after the soy protein relative to the animal protein. Isoflavones had no significant effect on TG and TGFA-FSR. Isoflavones reduced total cholesterol levels by 3.1% (P = 0.009) but had no significant effect on LDL, HDL cholesterol levels, or FC-FSR. These data demonstrate that dietary protein type modulates circulating TG and cholesterol levels in hypercholesterolemic individuals by distinct mechanisms.

Aged↗

Metabolism of defined structured triglyceride particles compared to mixtures of medium and long chain triglycerides intravenously infused in dogs.

The present study aimed to determine whether including medium-chain fatty acids (MCFA) in specifically designed structured triglycerides (STG) with a MCFA in sn-1 and sn-3 positions and a long-chain (LC) FA in sn-2 position (MLM) would lead to different effects on plasma lipids and FA distribution into plasma and tissue lipids by comparison to a mixture of separate MCT and LCT molecules (MMM/LLL). The fatty acid (FA) composition was comparable in both lipid emulsions. Lipids were infused over 9h daily, in 2 groups of dogs (n = 6 each), for 28 days as a major component (55% of the non-protein energy intake) of total parenteral nutrition (TPN). Blood samples were obtained on specific days, before starting and just before stopping TPN. The concentration of plasma lipids was measured before starting and before stopping TPN on days 1, 2, 3, 4, 5, 8, 10, 12, 16 and 28. Biopsies were obtained from liver, muscle and adipose tissue 15 days before starting, and again on the day following cessation of TPN. In addition, the spleen was removed after the TPN period. FA composition in plasma and tissue lipids was analysed by gas liquid chromatography in different lipid components of plasma and tissues. No differences in either safety or tolerance parameters were detected between both lipid preparations. A lower rise of plasma TG (P < 0.05) was observed during MLM infusion, indicating a faster elimination rate of MLM vs MMM/LLL emulsion. In spite of the differences of TG molecules which would be assumed to affect the site of FA delivery and metabolic fate, FA distribution in phospholipids (PL) of hepatic and extrahepatic tissues did not substantially differ between both emulsions.

Animals↗

Plasma triglyceride levels are higher in nephrotic than in analbuminemic rats despite a similar increase in hepatic triglyceride secretion.

The relative contributions of increased hepatic secretion of triglyceride (TG) and decreased TG catabolism to hypertriglyceridemia in the nephrotic syndrome, and their relationship to urinary protein loss and reduced plasma colloid osmotic pressure (pi) remain unclear. We measured the activity of acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), two key enzymes of fatty acid synthesis in hepatic cytosol, in fed control rats, in rats with congenital analbuminemia (NA) that are free of proteinuria, and in rats with adriamycin-induced nephrotic syndrome (ADR). Both NA and ADR rats had decreased pi (respectively 13.2 +/- 0.3 and 10.7 +/- 0.4 mm Hg vs. control rats 18.3 +/- 0.7 mm Hg, P < 0.05), but only ADR rats had increased plasma TG (5.8 +/- 2.6 mmol/liter vs. 1.5 +/- 0.2 mmol/liter in both control and NA rats, P < 0.05), and were proteinuric: 811 +/- 45 mg/day, P < 0.01 versus control and NA rats. Total cytosolic ACC activity, expressed per g body weight, was increased in both NA and ADR rats by 45% and 39%, respectively (P < 0.05). Total FAS activity was increased by 65% and 115% in NA and ADR rats, respectively (P < 0.05). Thus low pi was consistently associated with an increase in total ACC and FAS activities in the livers of fed rats. However, low pi was consistently associated with an increase in plasma TG only in ADR rats. Hepatic TG secretion rates, measured in vivo after blocking lipolysis with Triton WR-1339 in fasting animals, were increased by 33% in both ADR and NA rats as compared to controls (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗