The development of ketogenesis at birth in the rat

In the suckling newborn rat, blood ketone bodies begin to increase slowly 4h after birth and then rise sharply between 12 and 16h, whereas the major increase in plasma non-esterified fatty acids and liver carnitine occurs during the first 2h of life, parallel with the onset of suckling. In the starved newborn rat, which shows no increase in liver carnitine unless it is fed with a carnitine solution, the developmental pattern of the ketogenic capacity (tested by feeding a triacylglycerol emulsion, which increases plasma non-esterified fatty acids by 3-fold) is the same as in the suckling animal. This suggests that the increases in plasma non-esterified fatty acids and liver carnitine seen 2h after birth in the suckling animal are not the predominant factors inducing the switch-on of ketogenesis. Injection of butyrate to starved newborn pups resulted in a pattern of blood ketone bodies which was similar to that found after administration of triacylglycerols, but, at all time points studied, the hyperketonaemia was more pronounced with butyrate. It is suggested that, even if the entry of long-chain fatty acids into the mitochondria is a rate-limiting step, it is not the only factor controlling ketogenesis after birth in the rat. As in the adult rat, there is a reciprocal correlation between the liver glycogen content and the concentration of ketone bodies in the blood.     

Effect of fluoxetine on the plasma concentrations of clozapine and its major metabolites in patients with schizophrenia

Triglyceride levels and free fatty acid metabolism are influenced by body fat distribution. To test whether the pattern of fat distribution in obese subjects results in distinct insulin mediated suppression of non-esterified fatty acids which could account for differences in plasma triglycerides, we studied 59 obese subjects who were classified according to waist-to-hip ratio. Non-esterified fatty acids and insulin response to a 75 g oral glucose tolerance test were higher in abdominal obesity. Total non-esterified fatty acids response, after adjustment for sex, showed a positive association with waist-to hip ratio (r = 0.292; p < 0.05). The abdominal obese group had higher fasting triglycerides (1.74+/-0.83 versus 1.11+/-0.71 mmol/L; p = 0.003) and lower glucose/insulin ratio (5.2+/-2.3 versus 7.1+/-2.4; p = 0.003). Stepwise multiple regression analysis showed that triglyceride levels are explained by fasting and 120 min non-esterified fatty acids and by glucose/insulin ratio. We conclude that abdominal obesity is associated with a higher resistance to insulin mediated suppression of non-esterified fatty acids in obese subjects. Variation of triglyceride concentrations in obesity is dependent on both fasting and 120 min non-esterified fatty acids as well as on insulin sensitivity to glucose utilization.     

Lipoprotein lipase activity and its relationship to high milk fat transfer during lactation in grey seals

Lipoprotein lipase regulates the hydrolysis of circulating triglyceride and the uptake of fatty acids by most tissues, including the mammary gland and adipose tissue. Thus, lipoprotein lipase is critical for the uptake and secretion of the long-chain fatty acids in milk and for the assimilation of a high-fat milk diet by suckling young. In the lactating female, lipoprotein lipase appears to be regulated such that levels in adipose tissue are almost completely depressed while those in the mammary gland are high. Thus, circulating fatty acids are directed to the mammary gland for milk fat production. Phocid seals serve as excellent models in the study of lipoprotein lipase and fat transfer during lactation because mothers may fast completely while secreting large quantities of high fat milks and pups deposit large amounts of fat as blubber. We measured pup body composition and milk fat intake by isotope (deuterium oxide) dilution and plasma post-heparin lipoprotein lipase activity in six grey seal (Halichoerus grypus) mother-pup pairs at birth and again late in the 16-day lactation period. Maternal post-heparin lipoprotein lipase activity increased by an average of four-fold by late lactation (P = 0.027), which paralleled an increase in milk fat concentration (from 38 to 56%; P = 0.043). Increasing lipoprotein lipase activity was correlated with increasing milk fat output (1.3-2.1 kg fat per day) over lactation (P = 0.019). Maternal plasma triglyceride (during fasting) was inversely correlated to lipoprotein lipase activity (P = 0.027) and may be associated with the direct incorporation of long-chain fatty acids from blubber into milk. In pups, post-heparin lipoprotein lipase activity was already high at birth and increased as total body fat content (P = 0.028) and the ratio of body fat: protein increased (P = 0.036) during lactation. Although pup plasma triglyceride increased with increasing daily milk fat intake (P = 0.023), pups effectively cleared lipid from the circulation and deposited 70% of milk fat consumed throughout lactation. Lipoprotein lipase may play an important role in the mechanisms involved with the extraordinary rates of fat transfer in phocid seals.     

Electrophoretic patterns of serum albumins collected from different blood vessels

Rabbit sera collected from different blood vessels, e.g. vena renales, vena mesenterica, vena portae, vena hepatica and aorta, were electrophoresed in an urea-containing polyacrylamide gel. The albumin fraction was separated into 5-6 sub-bands. The profile of these sub-bands (electrophoretic pattern) of the sample from one blood vessel differed from that of another blood vessel. Especially, the electrophoretic pattern of serum collected from the renal vein 2h after deprivation of food differed from that of other blood vessels. Free fatty acid concentrations of each sample were also measured, and differences in these levels were observed in sera collected from different blood vessels. However, the fatty acid concentrations in serum from the renal vein were not low enough to permit detection of any abnormality in electrophoretic pattern in the albumin. This suggests the possibility of decreased concentration of lysolecithin in the renal vein which binds to albumin and changes the electrophoretic mobility of albumin, as do the free fatty acids.     

Medical and health impact of complex emergencies: implications for the International Society of Nephrology Disaster Relief Task Force

The aim of the present study was to measure whole body glucose uptake (M) and oxidation rate by euglycaemic hyperinsulinaemic clamp and indirect calorimetry in 7 morbidly obese subjects (BMI > 40 kg/m2) at three time points: before bilio-pancreatic diversion (BPD) surgery (Ob); 3 months after surgery POI; and after reaching stable body weight, at least 2 years after surgery POII. A group of 7 control subjects (C), matched groupwise for sex, age and BMI with POII patients, was also studied. The M value at POI was significantly higher than at Ob (49.12 +/- 8.57 vs 18.14 +/- 8.57 mumol.kg-1.min-1). No statistical difference was observed between the POII and C groups. Similarly, glucose oxidation rate was significantly increased at POI with respect to Ob (24.2 +/- 7.23 vs 9.42 +/- 3.91 mumol.kg-1.min-1) and was not significantly different between POII and C. Basal levels of non-esterified fatty acids (NEFA) decreased significantly both from Ob to POI and from POI to POII (1517.1 +/- 223.9 vs 1039.6 +/- 283.4 vs 616.0 +/- 77.6 mumol.1(-1). The same applied to basal plasma triglycerides (2.07 +/- 0.77 vs 1.36 +/- 0.49 vs 0.80 +/- 0.19 g.1(-1). Weight decreased mainly in the late postoperative period (POI to POII 124.28 +/- 11.22 to 69.71 +/- 11.78, 83% of total decrement), rather than in the early postoperative period (Ob to POI 135.25 +/- 14.99 to 124.28 +/- 11.22 kg, 17% of total decrement). We also report the clinical case of a young woman of normal weight, who underwent BPD for chylomicronaemia (secondary to familial lipoprotein lipase deficiency), whose M value, plasma insulin and blood glucose levels were normalized upon normalization of serum NEFA and triglyceride levels as determined by the therapeutic lipid malabsorption. In conclusion, in obese diabetic patients lipid malabsorption induced by BPD causes a definite enhancement of insulin sensitivity and glucose tolerance. This improvement in metabolism is noticeable before the surgery has major effects on body weight. These observations suggest that lowered plasma lipids, rather than weight loss per se, are the cause of the reversibility of insulin resistance.     

Hyperinsulinemia, hyperproinsulinemia and insulin resistance in the metabolic syndrome

For better comprehension of the metabolic syndrome, it is necessary to differentiate the effect of insulin on glucose metabolism on the one hand, and on other metabolic activities on the other hand. Whereas glucose utilization is affected by insulin resistance, the effect of insulin on lipid metabolism, ion and aminoacid transport does not seem to be diminished. Lipid metabolism, however, seems to play a crucial role in the induction of the vicious cycle. Increased energy and fat ingestion may be due to an increased number of galanin secreting cells in the hypothalamus. The excessive fat intake results in an increased rate of release of insulin and increased influx of triglycerides into the blood. From these triglycerides an excess of free fatty acids is released by the action of lipoprotein lipase. The increased plasma free fatty acid level then results in insulin resistance affecting glucose metabolism. Also, these free fatty acids may impair the secretion of insulin. Induction of insulin resistance results in higher glucose levels, which may cause hyperinsulinemia. Hyperinsulinemia maintains the elevation of triglycerides. When diabetes becomes overt and elevated glucose levels prevail, the hyperinsulinism acts on the metabolic pathways which are still sensitive to insulin, namely lipid metabolism, aminoacid transport and ion transport.     

Effects of ID-540 on averaged photopalpebral reflex in man

Twelve hyperlipidemic patients on long term treatment with a lipid lowering diet enriched in polyunsaturated fatty acids and with clofibrate were supplemented with vitamin E (400 mg/day). The effect on serum lipoprotein concentration, plasma lipid fatty acid composition, and adipose tissue lipoprotein lipase activity was studied. No additional lipid-lowering effect was registered during a treatment period of 4 months. A slight increase in total serum cholesterol concentration and in high density lipoprotein concentration was probably attributable to seasonal variations in serum lipoprotein concentrations. No major changes of fatty acid composition in plasma cholesteryl esters or triglycerides were recorded. However, an increased relative amount of arachidonic acid and a reduced amount of palmitic acid in the plasma phospholipids after 2 months was possibly caused by the vitamin E therapy.     

Seasonal rhythm of free tryptophan and nonesterified fatty acids in the blood of healthy subjects (author's transl)

During one year, free and total tryptophan, tyrosine and non-esterified fatty acids were determined in the blood of eight healthy volunteers. No clear seasonal rhythm appeared for any of these parameters. But over this period, the following significant correlations were found: total tryptophan-free tryptophan; total tryptophan-tyrosine; free tryptophan-tyrosine. For the individuals, the quotient tyrosine-tryptophan showed to be constant during this year.     

Changes in hepatic fatty acid degradation and blood lipid and ketone body content during development of the rat

The following have been measured during the development of the laboratory rat: the rate of oxidation of palmitoylcarnitine, decanoylcarnitine, and 14C-palmitate by liver mitochondria; the concentrations of ketone bodies in the blood; the plasma concentrations of non-esterified fatty acids, glycerol, and triglyceride. In each case, a rise after birth and a fall at weaning were observed. These changes can be correlated with the dietary changes which occur at these times. However, during the suckling period, when a constant high fat content diet is consumed, further marked changes in the parameters measured were observed which cannot be related to nutritional factors.     

Acute modulation of rat hepatic lipid metabolism by sulphur-substituted fatty acid analogues

A single oral dose of two 3-thia (3-thiadicarboxylic and tetradecylthioacetic acids) and of 4-thia (tetradecylthiopropionic acid) fatty acids were administered to normolipidemic rats and their effects on lipid metabolism over a 24 hr period were studied. All three thia fatty acids could be detected in plasma 2 hr after treatment. Tetradecylthioacetic and tetradecylthiopropionic acids were detected in different hepatic lipid fractions but were incorporated mainly into hepatic phospholipids. Two hours after administration hepatic mitochondrial beta-oxidation and the total liver level of long-chain fatty acyl-CoA increased with a concomitant decrease in saturated fatty acids, total hepatic malonyl-CoA and plasma triacylglycerol levels in the 3-thia fatty acid groups. Tetradecylthiopropionic acid administration caused a decrease in mitochondrial beta-oxidation and an increase in plasma triacylglycerol at 24 hr. The activities of key lipogenic enzymes were unaffected in all treatment groups. Plasma cholesterol level was reduced only at 8 hr in 3-thiadicarboxylic acid treated rats although 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase was suppressed already at 2, 4, 8 and 12 hr. The results show that thia fatty acids are rapidly absorbed and are systemically available after oral administration but the 3-thia fatty acids reached systemic circulation more slowly and less completely than the 4-thia fatty acid. Very low levels of the thia fatty acids are detected in plasma 24 hr after a single administration. They are incorporated into all hepatic lipid classes, especially phospholipids. Rapid incorporation of a non beta-oxidizable thia fatty acid into hepatic lipids may cause a diversion of other fatty acids from glycerolipid biosynthesis to mitochondrial beta-oxidation. Stimulation of mitochondrial beta-oxidation and suppression of HMG-CoA reductase are primary events, occurring within hours, after 3-thia fatty acid administration. The hypotriglyceridemic effect of the 3-thia fatty acids observed at 2-4 hr is independent of the activities of key lipogenic and triacylglycerol synthesising enzymes.     

Release of nonesterified fatty acids during cerulein-induced pancreatitis in rats

During acute pancreatitis, data obtained in vitro suggest that pancreatic lipase, acting on circulating or tissular triglycerides, might generate nonesterified fatty acids (NEFA) that could promote pancreatic and fat tissue necrosis. This work determined whether NEFA were actually produced in vivo in pancreatic tissue and in blood during cerulein-induced pancreatitis in rats. Intraperitoneal injections of cerulein induced pancreatitis. To promote the possible NEFA release by pancreatic lipase, a venous infusion of human very low density lipoprotein (VLDL) was used to cause hypertriglyceridemia. NEFA were measured in portal and aortic blood and in tissue extracts prepared from pancreas homogenates. NEFA did not increase either in peripheral or in portal blood. In pancreatic tissue, NEFA levels did not differ from controls. The major hypertriglyceridemia produced by human VLDL intravenous infusion neither altered the course of the disease nor promoted plasma NEFA release. The role commonly attributed to NEFA in acute pancreatitis seems questionable.     

Phospholipid transfer between plasma and platelets in vitro

Washed rabbit platelets were resuspended in plasma in which all of the major phospholipids had been isotopically labeled by injection of 32PO4 into rabbits. At certain time intervals during a 6-hr incubation at 37 degrees C, aliquots were removed from the incubation mixture and the platelets were isolated and subjected to lipid extraction and phospholipid analysis. A continuous rise in platelet non-lipid-bound and lipid-bound radioactivity was observed through-out the incubation period. Two platelet phospholipids, lecithin and lysolecithin, were significantly labeled, whereas little or no labeling of the other phospholipids was found. There was no detectable change in total or individual platelet phospholipid content. At 6 hr, 4% of total platelet phospholipid, 43% of platelet lysolecithin, and 7% of platelet lecithin were labeled. Platelets incubated in plasma from rabbits with diet-induced hyperlipidemia took up and incorporated significantly more label into their phospholipids than did platelets in normal plasma. Labeling of both platelet lysolecithin and lecithin could be due to uptake and metabolism of plasma lysolecithin by platelets. However, labeling of platelet lecithin could at least in part be the result of direct exchange of this phospholipid with the plasma. Uptake and incorporation of endogenous plasma lysolecithin by platelets and, possibly, direct exchanged of platelet lecithin may be important mechanisms in the modification by plasma lipids of platelet membrane phospholipid fatty acid composition and platelet function.     

Definition of the specific roles of lysolecithin and palmitic acid in altering the susceptibility of dipalmitoylphosphatidylcholine bilayers to phospholipase A2

Bilayers composed of phosphatidylcholine initially resist catalysis by phospholipase A2. However, after a latency period, they become susceptible when sufficient reaction products (lysolecithin and fatty acid) accumulate in the membrane. Temperature near the main bilayer phase transition and calcium concentration modulate the effectiveness of the reaction products. The purpose of this study was to examine the individual contributions of lysolecithin and palmitic acid to the susceptibility of dipalmitoylphosphatidylcholine vesicles and to rationalize the effects of temperature and calcium. Various fluorescent probes (Prodan, Laurdan, pyrene-labeled fatty acid, and dansyl-labeled phospholipid) were used to assess changes in the ability of the reaction products to perturb the bilayer and to affect the interactions with the enzyme. Un-ionized palmitic acid decreased bilayer polarity and perturbed the membrane surface exposing some of the Prodan to bulk water. Lysolecithin increased bilayer polarity and the rate of dipolar relaxation in response to the excited states of Laurdan and Prodan. A combination of the individual contributions of each product was observed when palmitic acid and lysolecithin were present together at low calcium, and the effects of lysolecithin dominated at high calcium. Palmitic acid, but not lysolecithin, promoted the binding of phospholipase A2 to the bilayer surface in the absence of calcium. Lysolecithin reduced the ability of fatty acid to enhance binding apparently by altering the structure of fatty acid domains in the membrane. Furthermore, increased temperature and ionization of the fatty acid tended to cause segregation of bound phospholipase A2 into domains poor in phospholipid content which presumably impeded bilayer hydrolysis. In contrast, un-ionized palmitic acid and lysolecithin promoted hydrolysis by augmenting a step distal to the adsorption of enzyme to the bilayer. This kinetic response to lysolecithin was calcium-dependent. A model accounting for these varied influences of the reaction products is presented.     

Lipoprotein lipase transport in plasma: role of muscle and adipose tissues in regulation of plasma lipoprotein lipase concentrations

Lipoprotein lipase (LPL) is synthesized in tissues involved in fatty acid metabolism such as muscle and adipose tissue. LPL is also found in the circulation, but is mostly lipolytically inactive. The proportion of active circulating LPL increases after a fatty meal. We investigated the release of active and inactive LPL from adipose tissue and muscle in the fasting and postprandial states. Arteriovenous concentration gradients of LPL across adipose tissue and forearm muscle were measured in male subjects before and after a fat-rich meal (n = 7) and before and during infusion of a triacylglycerol emulsion (Intralipid) (n = 6). Plasma LPL activity rose after the meal and more so during Intralipid infusion. Plasma LPL mass (>95% inactive LPL) increased after the meal but decreased after Intralipid infusion. In the fasting state (n = 13) muscle efflux of LPL activity was 0.263 +/- 0.098 mU/min per 100 ml of muscle tissue whereas there was an influx of LPL activity to adipose tissue of 0.085 +/- 0.100 mU/min per 100 g of adipose tissue (P < 0. 02 muscle vs. adipose tissue). Similarly in the postprandial state only muscle released LPL activity. Both tissues released LPL mass. In the fasting state efflux was 17.8 +/- 8.8 ng/min per 100 ml muscle and 55.2 +/- 21.3 ng/min per 100 g of adipose tissue (P < 0. 05 muscle vs. adipose tissue). Release of LPL, either active or inactive, was not correlated with levels of non-esterified fatty acids or plasma triacylglycerol. In conclusion, there is a substantial release of LPL from adipose tissue and muscle, most of which is inactive. A small proportion of active LPL seems to be redistributed from muscle to adipose tissue.     

Characteristics and clinical application of a radiometric Escherichia coli-based phospholipase A2 assay modified for serum analysis

Determination of activities of phospholipase A2 (PLA2) in human sera was based on the hydrolysis of phospholipids from [1-14C]oleic acid-labeled Escherichia coli biomembranes. The E. coli membranes served as substrate specifically for the PLA2 of human serum and were essentially resistant to other lipases in human sera, i.e., lipoprotein lipases, hepatic triacylglycerolipase, or pancreatic lipase in acute pancreatitis. Exchange of phospholipids between the serum and the biomembrane compartment aggravates the determination of PLA2 activity in human serum, which is naturally rich in phospholipids. In our modified E. coli assay, which overcomes these difficulties, the main substrate components phosphatidylethanolamine (70%) and cardiolipin (25%) were > 90% labeled in the sn-2 position. Fatty acids released by PLA2 activity were eluted from an aminopropyl solid-phase column directly into scintillation vials, where the radioactivity was counted. The ratio of [1-14C]oleic acid to released total fatty acids was used to calculate true enzymatic activity. The linear assay range extended from 0 to 3.6 U/L (0-60 nkat/L), with a detection limit of < 0.03 U/L (< 0.5 nkat/L). Within-assay imprecision (CV) was < 6% and between-assay is < 10% over the whole activity range. The normal range for men was 0-0.44 U/L (0-7.33 nkat/L) and for women 0.044-1.11 U/L (0.73-18.4 nkat/L). Patients with septicemia, pancreatitis, acute respiratory distress syndrome, or other severe diseases had PLA2 values up to 540 U/L (9000 nkat/L).     

Biochemical parameters in athletes before and after having run 160 kilometres

A number of biochemical and haematological parameters, including plasma electrolytes, parameters of hepatic and renal function, plasma enzymes and free fatty acids were measured in 13 athletes before and after a 160-km 24-hour race. The runners were divided into 2 groups: group A, who competed the 160 km within 24 hours and group B, who either ran for 24 hours, or who retired before completing the distance. Minimal changes were found in the plasma electrolyte patterns in either group, whereas blood urea and creatinine levels increased during the race. The plasma enzymes increased to varying extents, the greatest increases being in lactic dehydrogenase, aspartate aminotransferase and the skeletal muscle specific MM isoenzyme of creatinine phosphokinase. Total bilirubin also increased, but no conclusive evidence of hepatic decompensation was found. Plasma free fatty acids levels were very markedly raised in 12 of the runners, the highest increases occurring in group A. All runners ingested carbohydrate during the race and this probably explains why the blood glucose levels increased slightly but remained within normal limits in all the athletes at the end of the race.     

Coordinated release of acylation stimulating protein (ASP) and triacylglycerol clearance by human adipose tissue in vivo in the postprandial period

The objective of this study was to determine whether Acylation Stimulating Protein (ASP) is generated in vivo by human adipose tissue during the postprandial period. After a fat meal, samples from 12 subjects were obtained (up to 6 h) from an arterialized hand vein and an anterior abdominal wall vein that drains adipose tissue. Veno-arterial (V-A) gradients across the subcutaneous adipose tissue bed were calculated. The data demonstrate that ASP is produced in vivo (positive V-A gradient) With maximal production at 3-5 h postprandially. The plasma triacylglycerol (TAG) clearance was evidenced by a negative V-A gradient. It increased substantially after 3 h and remained prominent until the final time point. There was, therefore, a close temporal coordination between ASP generation and TAG clearance. In contrast, plasma insulin and non-esterified fatty acid (NEFA) had an early (1-2 h) postprandial change. Fatty acid incorporation into adipose tissue (FIAT) was calculated from V-A glycerol and non-esterified fatty acid (NEFA) differences postprandially. FIAT was negative during the first hour, implying net fat mobilization. FIAT then became increasingly positive, implying net fat deposition, and overall followed the same time course as ASP and TAG clearance. There was a direct positive correlation between total ASP production and total FIAT (r = 0.566, P < 0.05). These data demonstrate that ASP is generated in vivo by human adipocytes and that this process is accentuated postprandially, supporting the concept that ASP plays an important role in clearance of TAG from plasma and fatty acid storage in adipose tissue.     

Plasma membrane phospholipid fatty acid composition of cultured skin fibroblasts from schizophrenic patients: comparison with bipolar patients and normal subjects

Recent studies have found lower red cell plasma membrane contents and composition of the long chain polyunsaturated essential fatty acid derivatives, particularly arachidonic acid and docosahexaenoic acid, in a subgroup of chronic schizophrenic patients. These fatty acids are particularly enriched in the brain. Red blood cell levels of fatty acids are influenced by diet, medications, and other factors. Cell plasma membrane compositions of arachidonic and docosahexaenoic acids were therefore examined in cultured skin fibroblasts from 12 schizophrenic patients, 8 of whom were drug-naive and in a first episode of psychosis, 6 bipolar patients, and 8 normal control subjects. Docosahexaenoic acid as well as total n-3 essential fatty acid contents were significantly lower in cell lines from schizophrenic patients than in cell lines from bipolar patients and normal subjects, with no difference between the latter two groups. Arachidonic acid levels did not differ across the groups. The essential fatty acid profile observed is consistent with deficient delta-4 desaturase activity in schizophrenic patients.     

Dietary linoleic acid increases and palmitic acid decreases hepatic LDL receptor protein and mRNA abundance in young pigs

The present study was conducted to determine the effects of dietary fatty acids on hepatic LDL receptor (LDLr) protein abundance and mRNA levels. Sixty pigs were randomized into 10 groups and fed corn-soybean meal diets containing three cholesterol levels (0.25%, 0.5%, and 1.0%, w/w) with no added fat, or fats rich (30% of calories) in palmitic acid or linoleic acid. A control group was fed the base diet with no added fat. After 30 days, plasma LDL-cholesterol (LDL-C) levels increased as the dietary cholesterol increased (P < 0.05); however, there was no significant effect of either fatty acid. Dietary fatty acids, however, had distinctly different effects on hepatic LDLr protein (analyzed by ELISA) and mRNA (analyzed by Northern blot) abundance. When pigs consumed diets containing 0.25% cholesterol, linoleic acid increased hepatic LDLr protein 40% whereas palmitic acid reduced it 40% (P < 0.05). These changes in LDLr protein abundance were accompanied by parallel changes in hepatic LDLr mRNA; linoleic acid increased LDLr mRNA 2-fold (P < 0.01), whereas palmitic acid decreased it 60% (P < 0.01). The differential effects of fatty acids on LDLr expression were only observed at 0.25% cholesterol, suggesting that higher intakes of cholesterol have a dominant and repressive effect on regulation of LDLr expression. Cholesterol intake increased hepatic total cholesterol levels (P < 0.01) while dietary fatty acids had no effect on hepatic sterols. In summary, our results indicate that dietary linoleic acid and palmitic acid have markedly different effects on hepatic LDLr protein abundance that are mediated by differential effects on LDLr mRNA and protein levels. Further studies are needed to fully elucidate the molecular mechanisms by which fatty acids regulate LDLr mRNA and protein levels.     

6-methylprednisolone ''mini-pulses'': a new modality of glucocorticoid treatment in systemic onset juvenile chronic arthritis

Fatty acid ethyl esters (FAEE), esterification products of ethanol and fatty acids, have been implicated as mediators of ethanol-induced organ damage. Because cytosolic enzymes such as aspartate aminotransferase, lipase, and amylase appear in the blood after liver or pancreatic damage, we hypothesized that FAEE synthase, which is both cytosolic and membrane bound, is also released into the blood of patients with liver or pancreatic disease. We used a method involving thin-layer chromatography coupled with gas chromatography-mass spectrometry to reliably identify and quantify FAEE. In this study, we demonstrated that patients with liver or pancreatic disease release FAEE synthase into their plasma in amounts proportional to the amount of aspartate aminotransferase (r = 0.78), amylase (r = 0.65), and lipase (r = 0.63). These data indicate that liver and pancreatic damage results in release of FAEE synthase into the blood. The presence of FAEE synthase in plasma permits nonoxidative ethanol metabolism in the plasma.