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We studied ketonemia induced in rats by a single oral load of medium-chain triglycerides (MCT) (C8:0 50.5%, C10:0 48.0%, C12:0 1.0%). Medium-chain fatty acids, rather than being incorporated into the lipids synthesized by the liver, are oxidized there, with high production of ketone bodies. Severe and long-lasting hyperketonemia developed rapidly. With increased MCT loads, ketonemia also increased, although not linearly. The level of the hyperketonemia seemed equal in the two sexes. Ingestion of MCT by fasting rats caused an additional rise in ketonemia. Long-chain triglycerides were not ketogenic, since their constituent fatty acids are incorporated into lipids and are thus less subject to oxidation. Lipids induce less severe ketonemia in genetically obese rats than in normal-weight rats.

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.

The authors demonstrate a previously not described increase, in vivo, in a mean proportion of 70%, of the enzymatic activity of the clostridium collagenase in rats by erythromycin lactobionate. The pathogenesis of this phenomenon cannot yet be explained.

The effects of protein levels and types of fat in the diet on the metabolism of lean and obese Zucker rats were studied. For 40 days the rats were fed ad libitum one of four diets: two "usual protein" diets (19% protein by weight) with 19.4% triacylglycerols, either long chain (UP-LCT diet) or medium chain (UP-MCT diet); and two high protein (64% protein), carbohydrate-free diets, again with 19.4% triacylglycerols (HP-LCT and HP-MCT diets, respectively). The energy intakes of the obese rats decreased about equally on the HP-LCT, UP-MCT, and HP-MCT diets. The daily weight gain, which was high in the UP-LCT rats, was lower when carbohydrates were replaced by proteins, or when LCTs were replaced by MCTs; furthermore, when these two changes were made together, their beneficial effects on body weight were additive. The lipid gain, too, was high with the UP-LCT diet and lower both with the high protein diets and with the MCT diets; again combining the two amplified the two individual effects, so much that the final lipid concentration in the body was lowered, whereas the concentration of water increased. Hepatic acetyl CoA carboxylase activity was low when the diet supplied plenty of LCTs, but replacing carbohydrates with proteins in such a diet produced an additional decrease in this enzymatic activity. When either a normal protein or a high protein diet supplied MCTs in place of LCTs, acetyl CoA carboxylase activity was high and similar to that found with a high carbohydrate diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibitory effects of methysergide bimaleate on the collagenase of the Clostridium histolyticum have been established. Having previously shown the inhibitory action of serotonin on this bacterial collagenase, the authors have tested methysergide bimaleate as another inhibitor. After injection in the peritoneum of the rats of methysergide bimaleate and collagenase together, lesions are minimal or absent, in contrast with the dramatic effects of collagenase alone. This shows the antagonist role of methysergide bimaleate in regard to collagenase and suggest that methysergide bimaleate reduce the collagenolysis and may elucidate the possible occurrence of fibrotic lesions after treatment of migraine by methysergide bimaleate in man.

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 concentration 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 weeks 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.

The red cell uric acid concentration (E) is lower than its plasma concentration (P). In normal subjects the ration E/P is close to 0.7. Under experimental or pathological conditions (uricosuric treatment, fluid'diet, hemodialysis) causing changes in serum uric acid, the latter rises or falls proportionately less in red cells than in the plasma. There results a significant variation in the distribution of blood uric acid between the plasma and red cell compartments.

The authors showed previously that the effusions of the experimental polyseritis after intraperitoneal injections of trypsin and elastase, go from peritoneum to the pleural cavities and never from thorax to the peritoneum. The intraperitoneal injections of collagenase or of collagenase and trypsin can also cause polyseritis in the rat; but more often they provoke heavy hemorrhagic lesions of the wall of the abdomen and the diaphragm. Perforations of the diaphragm were observed in 8 rats of 32, with in 6, a intrathoracic hernia of the liver or the stomach. After the intrapleural injection of collagenase or of collagenase and trypsin, hemorrhagic lesions were seen in the thorax, but not in the abdomen. These facts are a new proof for the transdiaphragmatic propagation of the proteasic solutions injected in the peritoneum.

After reporting a case of a patient aged 69 years with an inoperable hypernephroma, in whom the presence of a polycythemia and a reduction in the provoked hyperlipemia curve was found to co-exist, the authors review the data in the published literature on the influence on the small intestine of cancers other than those in the gastro-intestinal system. Basing their comments on studies of hypernephromas, they stress that a reduction or delay in the hyperlipemia curve was found in 23 out of 28 patients. This abnormality can only be explained by hypotheses at the present time.

To test whether the property of medium-chain fatty acids (which have 6-12 carbon atoms) being incorporated only in small amounts into the various tissues of a living organism could be exploited to treat obesity, genetically obese Zucker rats and their lean littermates were fed a diet containing 20% medium-chain triacylglycerols (MCT) or long-chain triacylglycerols (LCT) for 10 weeks. MCT, as compared with LCT, had the following effects: 1) MCT did not diminish weight gain in either the nonobese or the obese rats; 2) they increased ketogenesis more in the former than in the latter; 3) they increased the concentration of triacylglycerols in the liver of the obese rats but not of the lean ones; 4) they decreased the concentration of cholesterol in the liver of the lean but not of the obese rats, and 5) they did not particularly affect the concentration of proteins, glucose and insulin in the blood. We therefore conclude that the influence of the genotype is much more important in the establishment of the biochemical characteristics of rats than is the nature of the fatty acids ingested. Replacing LCT in the diet with MCT did not correct any of the major metabolic disorders in obese rats and therefore cannot unaided constitute a solution to the problem of genetic obesity.

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.

In the rat peritoneal injections of collagenase or trypsin give rise to severe lesions. In our experience 20% of the animals remain intact. The frequency of lesions increases with older and heavier subjects. Moreover 25% of the rats who remained free of lesions after a first injection of collagenase resist to a second one. This shows that they are strongly protected against the enzyme. The exact nature and location of this protective mechanism are not known.

The influence of a diet including 18 per cent by weight of long-chain (LCT) or medium-chain (MCT) triacylglycerols on adipose tissue development, and on in-vitro adipose tissue triacylglycerol (TG) synthesis from glucose and palmitic acid, was studied using genetically obese, fa/fa, and control, Fa/-, Zucker rats. The adipose tissue mass was greater with the LCT diet than with either the MCT or control diets, but there was no significant difference between the MCT and control diets. TG synthesis from labelled substrates was not modified by the MCT diet when compared with the control, but was decreased by the LCT diet. The results suggested that the use of MCT in treating human obesity would necessitate levels too high to be therapeutically practical.

Twelve students with in apparent good health and fasting since the previous evening ingested 2 g of L-carnitine on one day and a placebo on another day in a single-blind trial. Six blood samples were taken during the 24 h following the ingestion. Their blood carnitine levels increased (the free form by 81%, and the total by 57%) to a maximum at about 3.5 h and then slowly decreased. Twenty-four hours after ingestion, blood carnitine concentrations had still not returned to their initial levels. In the time interval where the decay curve approximated a single exponential, the half-life of the carnitine appeared to be of the order of 15 h. During the 24 h after the administration of the 2 g of L-carnitine, 7% +/- 1% of it was eliminated in the urine. This work suggest that the daily administration during a long period, of 2 g of L-carnitine guarantee in a healthy subject blood carnitine concentrations superior to the normal levels. Its remains to determine if the dose is sufficient in the case where L-carnitine is given to ameliorate a primary or secondary lack of carnitine, or to lower a high level of lipids in blood.

We have previously demonstrated that intraperitoneal injections in rats of collagenase (from Clostridium histolyticum) are followed by severe lesions. Here we show that the injection of collagenase together with serotonin has no or only small effects. It appears to be partly due to serotonin. Creatinin and sulfate which form an injectable complex with serotonin have no influence on this phenomenon. The part of pH 4,4 of the injected solution is discussed. These facts suggest that serotonin may perhaps lower the collagenolysis and be thus responsible for the fibrogenetic effects of carcinoid tumors, many of these being characterised by their high production of serotonin.

The effects of a hyperlipidic diet containing medium-chain triacylglycerols (MCT) or long-chain triacylglycerols (LCT) and a control diet on the lipid composition of liver and adipose tissue in the Zucker fa/fa and Fa/- rat are compared. The weights of liver and adipose tissues of the rats fed the MCT diet are little different from those of the two other groups, but they are always higher in obese rats than in lean rats. After feeding the MCT diet, the amounts of the constituent octanoic and decanoic acids in liver and adipose tissues are higher in the fa/fa rat than in the Fa/- rat. The rate of lipogenesis in liver and adipose tissues of the obese rat fed the MCT diet remains high.