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A C Bach

Publications and source records attributed to A C Bach.

At least 19 recordsLinked to original sources

Phospholipid-rich particles in commercial parenteral fat emulsions. An overview.

In parenteral nutrition, the infusion of a fat EMU supplies both concentrated energy and covers the essential fatty acid requirements, the basic objective being to mimic as well as possible the input of chylomicrons into the blood. This objective is well met by the TAGRP of the EMU, which behave as true chylomicrons. However, commercial EMU also contain an excess of emulsifier in the form of PLRP. The number of these PLRP depends directly on the PL/TAG ratio of the EMU. They differ from the TAGRP by their composition (PL vs TAG and PL), their structure (PL in bilayer versus monolayer), and their granulometry (mean diameter 70-100 nm for PL vs 200-500 nm). The metabolic fate of the PLRP is similar in several ways to that of the TAGRP: exchanges of PL with the PL of the different cellular membranes and of the lipoproteins; captation of free CH from these same structures; and enrichment in apolipoproteins. However, because the TAGRP are the preferred substrates of the lipolytic enzymes, their clearance is much more rapid (half-life < 1 h) than that of the PLRP. As the infusion is continued, the PLRP end up accumulating and being transformed into LP-X (free CH/PL = 1; half-life of several days). As soon as the EMU is infused, the PLRP enter into competition with the TAGRP, in the lipolysis process as well as for sites of binding and for catabolism. The sites for catabolism of the two types of PAR are not the same: adipose tissues and muscles utilize the fatty acids and monoacylglycerols released by the lipolysis of the TAGRP; hepatocytes take up their remnants; the RES and the hepatocytes participate in the catabolism of the PLRP and the LP-X. Thus, prolonged infusion of EMU rich in PLRP leads to a hypercholesterolemia, or at least a dyslipoproteinemia, due to elevated LP-X, associated with a depletion of cells in CH, stimulating thus tissue cholesterogenesis. However, parenteral nutrition has evolved towards the utilization of EMU with a low PL/TAG ratio (availability of 30% formula) and less rapid delivery. For these reasons, the hypercholesterolemias that used to be observed with the 10% EMU have become much less spectacular or have even disappeared. It is interesting to note that patients on prolonged TPN, in particular those with a short small intestine, have weak cholesterolemia, reflecting a lowering of HDL and LDL not masked by elevated LP-X. At present, it seems difficult to produce sufficiently stable parenteral EMU devoid of PLRP. Notwithstanding, all the observations made since the introduction of the EMU in TPN are in favour of the use of PLRP-poor EMU. It is clear that the 10% formulas, and generally those with a PL/TAG ratio of 12/100, are ill-advised, especially in patients with a retarded clearance of circulating lipids.

Cholesterol

The usefulness of dietary medium-chain triglycerides in body weight control: fact or fancy?

Compared to long-chain triglycerides (LCT), medium-chain triglycerides (MCT) display some specific physico-chemical, and biological characteristics. Thus, MCT are currently used in clinical nutrition as energy-yielding substrates, and have been advocated for three decades as a useful mean for body weight reduction. This review encompasses most aspects of MCT metabolism arguing this slimming hypothesis pro and con. Findings in support of the opinion (lower energy density, control of satiety, rapid intrahepatic delivery and oxidation rates, poor adipose tissue incorporation) may be invalidated by counteracting data (stimulation of insulin secretion and of anabolic-related processes, increased de novo fatty acid synthesis, induced hypertriglyceridemia). The balance between these two opposing influences depends on the composition (energy intake, nature of ingredients, MCT/LCT ratio, octanoate/decanoate ratio) and duration of the regimen. Due to the high energy level (around 50%) of MCT necessary to achieve body weight loss, long-term compliance to such slimming regimens is unlikely in human nutrition.

Adipose Tissue

The selective mobilization of fatty acids is not based on their positional distribution in white-fat-cell triacylglycerols.

Fatty acids have been shown to be selectively mobilized from rat white fat-cells, whatever the dietary manipulations. For convenience, fatty acids have been classified as being highly, weakly and moderately mobilizable. The aim of this study was to examine whether the selective mobilization of fatty acids can be explained, even partly, by their positional distribution in adipose-tissue triacylglycerols (TAG) via the known specificity of hormone-sensitive lipase for the sn-1 and sn-3 positions. Adipose tissue was dietarily manipulated in order to obtain a wide spectrum of fatty acids, including large amounts of either very-long-chain polyunsaturated fatty acids (VLC-PUFA) or very-long-chain monounsaturated fatty acids (VLC-MUFA). The determination of fatty acid distribution in adipose tissue TAG was based on random formation of 1,2-diacyl-rac-glycerols by Grignard degradation, followed by synthesis of phosphatidic acids and hydrolysis in the sn-2 position by phospholipase A2. Regardless of the fatty acid composition and location of fat depots, highly (e.g. 18:4n-3 and some of the VLC-PUFA) and weakly (e.g. VLC-MUFA) mobilizable fatty acids were located mainly in the outer (sn-1 and sn-3) positions of the glycerol moiety (79.5% and 92.5% on average, respectively). Other fatty acids, which are rather moderately mobilizable, were more randomly distributed. We conclude that the selective mobilization of white-fat-cell fatty acids is not based on their positional distribution in TAG.

Adipocytes

Selectivity of fatty acid mobilization: a general metabolic feature of adipose tissue.

This study extends our earlier work (T. Raclot and R. Groscolas. J. Lipid Res. 34: 1515-1526, 1993), which showed that, under norepinephrine-stimulated lipolysis, fatty acids of rat retroperitoneal fat cells are selectively mobilized. The present study examines whether this selective mobilization of fatty acids 1) is based on their proportions in adipose tissue, 2) is a metabolic feature common to all adipose tissues, and/or 3) depends on the lipolysis-stimulating agent. Rat fat cells with two markedly different fatty acid compositions were isolated from four white adipose tissues and treated with three lipolytic agents. Fatty acid composition of in vitro released free fatty acids was compared with that of fat cell triacylglycerols, the ratio of percent in free fatty acid to percent in triacylglycerol being defined as the relative mobilization rate (RMR). The RMR of individual fatty acids was related to their molecular structure. It increased exponentially with unsaturation for a given chain length and decreased with increasing chain length for a given unsaturation. The selectivity of fatty acid mobilization was similar regardless of the fatty acid composition of adipose tissue, the tissue location, and the lipolytic agent used. Under conditions of stimulated lipolysis, the selectivity of fatty acid mobilization is therefore a general metabolic feature of adipose tissue. Fatty acids with 16-20 carbon atoms and 4 or 5 double bonds had the highest RMR (from 1.4 to > 5), whereas fatty acids with 20-22 carbon atoms and 0 or 1 double bond had the lowest RMR (from 0.3 to 0.7). For the other fatty acids, RMR was close to unity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Deaminase

Lipid composition and structure of commercial parenteral emulsions.

In order to study the influence of the phospholipid/triacylglycerol (PL/TG) ratio of parenteral emulsions on the distribution and the physico-chemical properties of their fat particles, commercial 10, 20 or 30% fat formulas were fractionated by centrifugation into an upper lipid cake (resuspended in aqueous glycerol) and a subnatant or mesophase, from which a PL-rich subfraction (d = 1.010-1.030 g/l) was purified by density gradient ultracentrifugation. Chemical and 31P-NMR analyses of these fractions indicated that at least two types of fat particles coexist in parenteral emulsions: (i) TG-rich particles (mean diameter: 330, 400, 470 nm in the 10, 20, 30% emulsion) which contain practically all the TG and esterified phytosterols of native emulsions, but only a fraction of their PL, unesterified cholesterol and phytosterols, and other minor lipids; (ii) PL-bilayer particles or liposomes (mean diameter: 80-100 nm) which are constituted with the remaining PL and relatively very small amounts of TG and other lipids. The higher the oil content of the emulsion, the lower the amount of these PL-rich particles, which represent the major particle population of the mesophase. Indeed, minute amounts of TG-rich particles (probably the smallest ones) are also present in the mesophase, even in the PL-rich subfraction which contains the bulk of liposomal PL. Since the PL-rich particles of the infused emulsion generate lipoprotein X-like particles, only the large TG-rich particles can be considered as true chylomicron counterparts.

Centrifugation, Density Gradient

Synthesis and NMR conformational analysis of a beta-turn mimic incorporated into gramicidin S. A general approach to evaluate beta-turn peptidomimetics.

The solution structure of a gramicidin S (GS) analog containing a beta-turn mimic [BTD4-5, Lys2.2']GS has been compared to that of native GS. The linear [BTD4-5, Lys2.2']GS was synthesized by solid phase methodology and the cyclized peptide was analyzed by NMR. In the peptide portion of [BTD4-5, Lys2.2']GS, the intramolecular hydrogen bonding pattern, inter-residue NOEs, including a transannular H alpha-H alpha NOE, and JN alpha coupling constants all describe a solution structure which is equivalent to that of native GS. These data confirm that the BTD group is a competent Type II' beta-turn mimic since it does not disrupt the native conformation of GS. It also supports the use of GS as a conformational model in which to test beta-turn mimics.

Amino Acid Sequence

The mesophase of parenteral fat emulsion is both substrate and inhibitor of lipoprotein lipase and hepatic lipase.

Six 10% and 20% parenteral fat emulsions were separated by centrifugation into two fractions: (1) a supernatant containing the bulk of triacylglycerols (Tg) as fat particles stabilized by phospholipids (PL); and (2) an infranatant, called mesophase, consisting essentially of PL (one third of the original PL in the 10% formula, one sixth in the 20% formula, in the case of emulsions containing 12 g PL.L-1) and small amounts of Tg and free sterols, probably in the form of liposomes. The lipolytic enzymes, lipoprotein lipase (LPL) and hepatic lipase (HL), involved in the Tg-rich lipoprotein clearance, hydrolyze both types of particles, although Tg-fat particles are their preferred substrate. Inactivated serum (providing apo C-II) is needed to ensure the maximum LPL hydrolysis rate of both types of particles. It partially inhibits the HL activity on the mesophase. Substrate of the lipolytic enzymes, the mesophase, is also an inhibitor of their activity, the inhibition being directly proportional to the amount of PL contained in the mesophase. This inhibition is of uncompetitive type. For LPL, it seems that the mesophase acts on a site distinct from that of the apo C-II binding site. These results partly explain the low PL clearance after a fat emulsion infusion. But in particular, they help to explain the lower clearance of a 10% emulsion (larger PL excess) compared with a 20% emulsion (with the same amount of Tg, but less PL excess).

Animals

Gram-negative bacteria sepsis in the rat and tissue lipolytic activity on LCT and MCT/LCT-based commercial parenteral emulsions.

The aim of this study was to evaluate the effect of a gram-negative bacteria sepsis on the activity of the enzymes lipoprotein lipase (LPL) and hepatic lipase (HL), involved in the clearance of circulating triacylglycerol-rich fat particles. Fasting rats were intravenously injected with NaCl9 g.l-1, live or heat-killed Pseudomonas aeruginosa bacteria. After 18 h the animals were killed. When compared to controls, the 2 treated groups showed an increase in body temperature, cholesterolemia, triglyceridemia and a decrease in ketonemia, proteinemia, albuminemia and in the in vitro activity of diaphragm, heart and adipose tissue LPL and of HL. The decrease in the enzyme activities occurred independent of the type of emulsion used as in vitro substrate, whether it was based on long-chain triglycerides or on medium- and long-chain triglycerides, but in any case the activity was lower with the first than with the second type of fat emulsion.

Animals

Long-chain versus medium and long-chain triglyceride-based fat emulsion in parental nutrition of severe head trauma patients.

In order to assess the metabolic value of medium-chain triglycerides (MCT) in severely stressed intensive care unit patients, two fat emulsions containing either long-chain triglycerides (LCT), or a mixture of 50% MCT and 50% LCT were compared in 24 head trauma patients over a 10 day period. Variations of serum triglyceride, non-esterified fatty acid, glycerol and phospholipid concentrations remained comparable after both lipid infusions. Bilirubin, alkaline phosphatase and transaminase plasma levels were altered in both groups without any significant differences or clinical consequences. Cumulative nitrogen balance remained negative (-10 g N. day-1 i.e. -100 g N. 10 days-1) and comparable in both groups. However, thyroxin-binding prealbumin concentrations increased significantly in patients receiving the MCT/LCT mixture. It is concluded that MCT might have a beneficial effect on visceral protein metabolism after trauma.

Blood Proteins

Activities of lipoprotein lipase and hepatic lipase on long- and medium-chain triglyceride emulsions used in parenteral nutrition.

Prolonged parenteral nutrition frequently includes lipid emulsions. This report investigates how emulsions containing triacylglycerols of different molecular weight affect the rate of clearance in vivo and the activity in vitro of the two enzymes responsible for this clearance: diaphragm lipoprotein lipase (LPL) and hepatic endothelial lipase (HL). Whatever their molecular weight, the triacylglycerols of the emulsions were hydrolyzed by LPL and HL. However, the reaction was faster with medium-chain triglycerides (MCT) than with long-chain triglycerides (LCT). To be active, LPL required the presence of serum (apolipoprotein CII); for maximum activity less serum was required for MCT than for LCT. In the case of HL, serum inhibited the effect on LCT but not on MCT. However, hydrolysis of emulsified triacylglycerols by LPL and HL required the presence of albumin as a transporter of the fatty acids released. Less albumin was needed for maximum activity with MCT than with LCT. In vivo, although MCT emulsions were eliminated more rapidly than LCT emulsions, the former resulted in a greater increase in plasma concentrations of triacylglycerols and free glycerol than did the latter. This is explained by the fact that MCT provides about 1.8 times more triacylglycerol molecules than the LCT. In vitro, LPL and HL hydrolyzed structured lipids (randomly esterified triacylglycerols of medium- and long-chain fatty acids) slightly less rapidly than they did control lipids, but there was no comparable difference in the blood lipid parameters examined in vivo. Because the MCT emulsions are cleared rapidly, their fatty acids are rapidly made available to the various tissues where they are oxidized.

3-Hydroxybutyric Acid

Fat emulsion particle size: influence on the clearance rate and the tissue lipolytic activity.

In lipid emulsions for parenteral use the mean particle diameter of the droplets in the 20% emulsions is larger than in the 10% emulsions. In long-chain triglyceride emulsions it is greater than in medium-chain triglyceride emulsions. As the particle diameter decreases, the total interfacial area increases, as does the lipoprotein lipase (LPL) and hepatic lipase (HL) activity. For a given quantity of triglycerides and phospholipids the lipolytic activity is proportional to the total interfacial area. A doubling of the phospholipid concentration is accompanied by a small reduction in the activity of both enzymes. In going from long-chain to medium-chain triglycerides, there is an acceleration in the clearance rate of infused lipid. For a similar emulsion, the clearance rate decreases as the particle size decreases. It seems plausible that the larger the mean droplet diameter, the greater the participation of the reticuloendothelial system in the clearance.

Animals

Solution structures of the rabbit neutrophil defensin NP-5.

Solution structures of the rabbit neutrophil defensin NP-5 have been determined by 1H nuclear magnetic resonance (n.m.r.) spectroscopy and distance geometry techniques. This 33 amino acid peptide is part of the oxygen-independent mammalian defense system against microbial infection. The structures were generated from 107 n.m.r. derived inter-residue proton-proton distance constraints. A distance geometry algorithm was then used to determine the range of structures consistent with these distance constraints. These distance geometry calculations employed an improved algorithm that allowed the chirality constraints to be relaxed on prochiral centers when it was not possible to make stereo-specific assignments of protons on these centers. This procedure gave superior results compared with standard distance geometry methods and also produced structures that were more consistent with the original n.m.r. data. Analysis of the NP-5 structures shows that the overall folding of the peptide backbone is well defined by the n.m.r. distance information but that the side-chain group conformations are generally less well defined.

Animals

Prolonged submaximal exercise and L-carnitine in humans.

Changes in the main physiological parameters and circulating indicators of carbohydrate, protein, lipid (and ketone body) metabolism were measured in ten exercising subjects before L-carnitine (L-carn) loading, after 4 weeks of daily loading with 2 g L-carn, and 6-8 weeks after terminating L-carn administration. Measurements were made on venous blood samples collected during each experiment at fixed time intervals over an initial rest of 45 min, 60 min bicycle exercise performed near 50% VO2max and 120 min recovery. Free and total plasma carnitine levels reached a plateau corresponding to an average rise of 25% for both fractions, 9-10 days after the beginning of the L-carn diet. These levels returned to their initial values 6-8 weeks after cessation of the supply. Generally L-carn supplementation did not significantly modify the physiological parameters and circulating metabolites. No distinct increase of the relative participation of endogenous lipids in the fuel supply of prolonged submaximal exercise was observed. In normal human subjects the increased demand for fatty acid oxidation resulting from exercise seems to be adequately supported by endogenous levels of carnitine.

Adult

Medium-chain triglycerides in parenteral nutrition in the newborn: a short-term clinical trial.

In order to study the effects of infusions of medium-chain triglycerides (MCTs) in newborns (2 to 4 weeks old), we administered these fats to patients requiring short-term (48 h) parenteral nutrition. The regimens provided glucose (10 g.kg-1 B.W..24 h), amino acids (1 g.kg-1 B.W..24 h), and, between 8.00 a.m. and 8.00 p.m. of each day, a 10% fat emulsion (1.5 g triglycerides.kg-1 B.W.). The one group (n = 10) received an emulsion containing long-chain triglycerides (LCTs), while the other group (n = 12) was given an MCT/LCT emulsion. No adverse reaction related to either emulsion occurred. Plasma Na, K, Ca and Cl levels and the capillary gasometry did not change during the trials. Plasma triglycerides, non-esterified fatty acids, and free glycerol were increased immediately at the end of the lipid infusion. Concerning triglycerides and non-esterified fatty acids, the increase was greater with the MCT/LCT emulsion than with the LCT emulsion but all values returned to normal within 12 h after the end of the fat infusion. The blood ketone body concentrations did not change and there was no ketonuria. Under our conditions, the MCT/LCT emulsion maintained the plasma glucose and urea levels better than the LCT emulsion.

Female

Carnitine supplementation and fat emulsion clearance and utilization.

The aim of the present work is to learn if intravenous administration of L-carnitine accelerates the clearance of a lipid emulsion. Intravenous fat tolerance tests have been done on rats (0.4 g triacylglycerols.kg-1 B.W.). Measurement of the light scattering index of the plasma permitted determination of the exogenous lipid concentration and thus allowed to represent the clearance curve of the infused emulsion. It was found that prior administration of L-carnitine (110, 160 or 560 mg.kg-1 B.W.) does not modify the clearance rate either of a long chain triglyceride emulsion or of a medium chain triglyceride based emulsion. The observed clearance in L-carnitine deficient animals, resulting either from intraperitoneal injections of D-carnitine (3 g.kg-1 B.W. for four days) or from a 6-months long diet of suboptimal amounts of precursor amino acids and vitamins for carnitine biosynthesis, was not reduced relative to the clearance in corresponding control animals. Also, the in vitro activities of the two enzymes involved in the clearance of the infused lipids, lipoprotein lipase (diaphragm and adipose tissue) and hepatic endothelial lipase, were unmodified by the L-carnitine.

Animals

Two-dimensional NMR studies of the antimicrobial peptide NP-5.

Nearly complete proton resonance assignment of the rabbit antimicrobial peptide NP-5 has been made from two-dimensional NMR data taken at a single temperature. The assignment procedure involved acquisition of phase-sensitive double-quantum-filtered correlation spectra, relayed coherence-transfer spectra, total correlation (homonuclear Hartmann-Hahn) spectra, double- and triple-quantum spectra, and nuclear Overhauser effect spectra. The combination of these complementary experiments simplified and accelerated resonance assignment of the peptide. Individual assignments were made at 20 degrees C for all amide and C alpha protons in the peptide, and for all nonlabile side-chain protons on 26 of the 33 amino acid residues in NP-5. Analysis of the proton-proton nuclear Overhauser effect connectivities, the slowly exchanging amide protons, and the proton chemical shifts in NP-5 indicates that the peptide has a stable, ordered structure in solution. These data also indicate that residues 19-29 in NP-5 are involved in an antiparallel beta-sheet that has a hairpin conformation.

Amino Acid Sequence

Metabolic effects of high-protein diets in Zucker rats.

The effects of dietary protein on the metabolism of proteins, carbohydrates, and especially, lipids were investigated in genetically obese Zucker rats and their lean siblings. For 40 days the rats received diets containing 15%, 64%, or 82% protein, included at the expense of cornstarch. In the obese animals, the high-protein diets led to decreased food intake and weight gain. While these diets decreased the activities of lipogenic enzymes along with the lipid gain, they did not decrease the final body-fat content. The increase protein intake stimulated hepatic ureogenesis and gluconeogenesis. Lipolysis was stimulated, as demonstrated by an accumulation of ketone bodies in the liver. Blood levels of triacylglycerols, free glycerol, and nonesterified fatty acids were concomitantly decreased, which suggests an accelerated turnover of lipids. Whatever the composition of the diet, total energy retention of the lean rats was always less than that of the obese rats. The changes observed on high-protein diets were essentially the same for the two groups, except that the final body-content of lipids in the lean rats was significantly lower. In the absence of exogenous carbohydrate, the lean rats were barely able to retain nitrogen and to maintain hepatic lipogenesis. Unlike the rats from other strains, the lean Zucker rats could not adapt to a low-carbohydrate diet; this failure may be due to a metabolic disorder.

Acetyl-CoA Carboxylase