André Bach

Restoration of the jejunal mucosa in rats refed after prolonged fasting.

To investigate the importance of body fuel depletion on gut rehabilitation after food deprivation, we compared the kinetics of jejunal mucosa alteration and restoration in rats that were refed after reaching different stages in body fuel depletion. Rats (P2) were refed while still in the so-called phase II, where body protein utilization is minimized, whereas rats (P3) were refed when they had reached the stage of increasing protein utilization (phase III). There was a significant decrease in total mass of intestine (P2, -30%; P3, -40%) and jejunal mucosa (P2, -52%; P3, -60%), as well in the size of the crypts (P2, -15%; P3, -36%) and villi (P2, -37%; P3, -55%). Structural changes of the mucosa included disappearance of some villi and a reduction in the size and number of crypts. Despite the larger morphological alterations in P3, the restoration of mucosa was as fast and complete after only 3 days of refeeding for both P2 and P3 rats. The respective roles of the mitosis pressure and of the lamina propria dynamics were studied. The rapid reversibility of the gut mucosal alterations due to fasting might constitute an integrative process.

Medium-Chain Triglyceride-Based Fat Emulsions: An Alternative Energy Supply in Stress and Sepsis

Medium-chain triglycerides (MCTs) and medium-chain fatty acids (MCFAs) have special physicochemical properties such as small molecular weight, small interfacial tension against water, and for the fatty acids, solubility in biological fluids. As a result the metabolic pathways followed by these fats in an organism are different and simpler, or identical but more rapid, than those followed by long-chain triglycerides (LCTs) and long-chain fatty acids (LCFAs). Consequently the MCTs have found numerous applications in oral or enteral nutrition and, more recently, in parenteral nutrition. The infusion of conventional fat emulsions in stress and sepsis is still controversial. A main question is whether an MCT supply can be beneficial for these patients. In this review, we will discuss different aspects of modified lipid and protein metabolism: exchanges between exogenous fat particles and lipoproteins; exogenous fat clearance, storage, and oxidation; reticuloendothelial system function; nitrogen balance; and hepatic function. For each of these perturbations, the MCT/LCT and structured lipid emulsions are theoretically capable to provide an appropriate solution. The efficiency of these emulsions has been demonstrated experimentally on animal models of stress and sepsis. However, the value of MCT-based fat emulsions for these pathological states has still to be ascertained by clinical studies.

Structure and metabolic fate of triacylglycerol- and phospholipid-rich particles of commercial parenteral fat emulsions

The lipid emulsions used in parenteral nutrition are constituted of particles rich in triacylglycerols (TAG) called artificial chylomicrons (200-500 nm in diameter; monolayer of phospholipids [PL] enveloping a TAG core) and PL-rich particles called liposomes (diameter inferior to 80 nm; bilayer of PL around an aqueous phase), which represent the excess emulsifier. Introduced into the circulation, the two populations of particles come into contact with circulating lipoproteins and cell membranes and experience the same overall fate: exchanges and transfers of lipids and apolipoproteins, enzymatic hydrolysis of TAG and PL, and internalization by different tissues. The relative importance of these different metabolic processes varies depending on the type of particle. The artificial chylomicrons undergo a hydrolysis of their TAG by lipoprotein lipase, with a release of fatty acids and formation of smaller particles of remnants, which are rapidly removed by the liver. In delivering fatty acids to the tissue, artificial chylomicrons fulfill an energy transport function similar to the natural chylomicrons. The liposomes hold little energy interest, and they also have deleterious effects when infused in excess. They inhibit the lipolysis of artificial chylomicrons and, by actively capturing endogenous cholesterol, they stimulate tissue cholesterogenesis and accumulate in the blood as lipoprotein-X, a long-lived abnormal lipoprotein. To limit as much as possible the metabolic perturbations due to the intravenous administration of exogenous PL, the emulsion has to be infused at a low rate, and should contain the minimal amount of excess PL.

Biological Parameters of the Blood in the Genetically Obese Zucker Rat

A study of the various biological parameters of the blood in the genetically obese Zucker rat, the nonobese Zucker rat, and the Wistar rat has revealed great similarity between the two latter types of animals. On the other hand, in genetically obese Zucker rats as compared with the nonobese ones, (1) the blood mass per unit of weight was lower; (2) the level of nitrogenous degradation compounds was the same; (3) the lipase activity was lower; (4) the levels of substances for which liver plays a crucial role--all lipid and protein fractions, glucose, and the enzyme GPT--were higher; (5) the levels of Ca, Zn, Fe, Cu and Pi were high; (6) the blood and bone-marrow cells were unremarkable.

Data on lipid metabolism in the genetically obese Zucker rat

Abstract We assayed various lipid fractions as well as some intermediate metabolites and adenine nucleotides in the liver and the blood of the genetically obese Zucker rat (fa/fa) and compared their values with the corresponding ones obtained for nonobese controls and for Sprague-Dawley rats. Results for the two latter groups were similar, and differed greatly from those for the obese rats. The obese rats had hepatomegaly due mainly to high levels of triglycerides. The plasma of the obese animals contained high levels of triglycerides, phospholipids, cholesterol, and nonesterified fatty acids. Obese rats had slightly higher levels of ketone bodies than nonobese rats. In the liver of obese rats, we observed a decreased level of citrate/g and an elevated malate level. Levels of adenine nucleotides were similar in all rats.

Age-related changes in biological parameters in Zucker rats

Changes in a number of morphological and biochemical parameters were observed in genetically obese Zucker rats and in lean controls between 3 and 58 weeks of age. By 3 weeks, the genetically obese rats had higher proportional (wt/100 g body wt) and absolute amounts of adipose tissue, hyperlipemia affecting all the lipid fractions, and hyperproteinemia compared to lean controls. Obesity, hepatomegaly, high concentrations of hepatic lipids and hyperinsulinemia did not appear until the fifth week. In obese animals, liver lipid concentration reached a maximum at 17 weeks of age and then declined. During this time, the triacylglycerol concentrations in the serum remained stable, whereas the cholesterol and phospholipid concentrations continued to increase. The glycogen concentration in obese animals increased, both absolutely and compared to lean controls, between the 12th and 43rd week of age. From weaning, the Zucker rats, compared to lean controls, exhibited characteristics of obesity (accumulation of adipose tissue, hyperlipemia and hyperproteinemia), which persisted to the age of 58 weeks.

Studies on the tolerance of medium chain triglycerides in dogs

Two groups of five conscious dogs received total parenteral nutrition (about 100 kcal/kg body weight per 24 hr) continuously for 96 hr (0.28 g triglycerides/kg body weight per hr, constituting more than 55% of the energy supply). The only difference between the two groups was the nature of the 20% lipid emulsion. In one group, this emulsion contained only long-chain triglycerides (LCTs), and in the other it contained a mixture (vol/vol) of medium chain triglycerides (MCTs) and LCTs. MCTs thus were given in an amount of about 30% of the total energy supplied. During infusion with the MCT/LCT mixture, C8, C10, and C12 fatty acids appeared in the total plasma fatty acids. When the infusion was stopped, the medium-chain fatty acids disappeared; those with shorter chains did so more rapidly. The plasma triglyceride clearance was faster for the MCT/LCT mixture than for the LCTs, whereas phospholipid and cholesterol clearance seemed slower for the MCT/LCT mixture. With this mixture, there was a slight increase in the plasma concentrations of ketone bodies, lactate, and pyruvate, and a slight decrease in plasma glucose. The MCT/LCT mixture was well tolerated, causing no discernible problems, and, in particular, no signs of narcosis or encephalopathy.

Intralipid 10%: Physicochemical Characterization

OBJECTIVES Parenteral fat emulsions contain two populations of particles: artificial chylomicrons rich in triacylglycerols (TAG), and liposomes (bilayer of phospholipids [PL] enveloping an aqueous phase). Centrifugation permits isolating the liposomes in the infranatant called mesophase. The aim of the present work was to better characterize this mesophase chemically and to view the particles it contains by electron microscopy. METHODS Electron microscopy (Philips 410) was performed after cryofracture on native 10% Intralipid, mesophase (centrifugation for 1 h at 27 000 g), and a liposome-enriched fraction (ring of density 1.010-1.030 g/l obtained after centrifuging mesophase in a KBr density gradient at 100 000 g for 24 h). The TAG and protein content of the mesophase was analyzed and the proteins partially characterized by immunodetection (Western-blot). RESULTS This electron microscope study of 10% Intralipid gives evidence for the coexistence of artificial chylomicrons (mean diameter, 260 nm) and liposomes (43 nm), the latter being smaller than expected and containing 8% w/w TAG after purification. The solubilization of TAG in PL bilayers (reported to be < or = 3.1% w/w) might have been increased in parenteral emulsions by the manufacturing process or/and the high TAG/PL ratio. Minute amounts of proteins have also been detected and partially characterized using a specific antibody raised against the human 7 kDa Anionic Polypeptide Factor (APF), known to strongly interact with PL in bile. CONCLUSIONS This work has shown that the size (mean diameter, 43 nm) of the liposomes present in 10% Intralipid is smaller than that usually assumed. Traces of hydrophobic proteins in the emulsion may account for certain allergic reactions sometimes observed in infused patients.

Plasma carnitine in women. Effects of the menstrual cycle and of oral contraceptives.

The plasma concentrations of carnitine were determined in a group of 35 women and 35 men admitted to a clinic, and in another group of 18 women during their menstrual cycle. The values found for the women (45.1 +/- 2.6 nmol/ml of free carnitine and 59.1 +/- 2.8 nmol/ml of total carnitine) were not significantly different from the values obtained in men (respectively 42.4 +/- 1.7 and 55.5 +/- 1.9 nmol/ml). No direct relationship between the free or total carnitine concentrations and the concentrations of circulating lipids could be demonstrated. During the menstrual cycle the plasma concentrations of free and total carnitine remained unchanged. Intake of oral contraceptives caused an elevation in blood triacylglycerols and decreases in the levels of luteinizing hormone, follicle-stimulating hormone, and free and total carnitine.