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Biomedical subjects

C A Barth

Publications and source records attributed to C A Barth.

At least 37 records · Page 2Linked to original sources

Difference of plasma amino acids following casein or soy protein intake: significance for differences of serum lipid concentrations.

There were significant differences of postprandial plasma concentrations for 8 amino acids (Cys, Val, Met, Leu, Tyr, Lys, Trp, and Arg) depending on whether pigs consumed a meal containing casein or isolated soy protein. The postprandial plasma amino acid pattern conformed with the amino acid composition of the dietary protein (except for Ser). The data, however, do not allow to conclude unambiguously, whether specific amino acids are responsible for the difference of serum cholesterol following casein or soy protein intake. Significant differences between casein- and soy-fed rats were observed regarding total and free plasma thyroxine and triiodothyronine concentrations. This observation can explain the accompanying different serum cholesterol concentrations. The different thyroid hormone concentrations were not paralleled by differences in TSH levels suggesting that dietary proteins affect thyroid function at the thyroid gland.

Amino Acids↗

Dietary protein and atherogenesis.

Different dietary proteins determine different serum cholesterol levels if fed in a semisynthetic diet to some, but not all, animal species. In one species, the rabbit, this metabolic response is elicited without adding high sucrose or cholesterol supplements that have to be added to rat or pig diets in order to cause a similar response. Eleven out of 13 studies show that casein and soy protein do not induce different serum cholesterol levels in normal man. More important, protein-induced differences of serum cholesterol concentrations have not been reported when appropriate nutritional methodology has been applied. We conclude that no protein-induced hypercholesterolemia is observed in primates, particularly not in the human species. Dietary recommendations urging the general public to reduce consumption of animal protein because of a higher atherogenicity are not supported by the present data. The biochemical basis of the metabolic responses has been studied by many investigators, but no convincing unifying concept has yet been identified. The recent observation of higher serum thyroxine concentrations following soy protein consumption (and vegetable protein in general) when compared to casein shed new light on this problem. This endocrine response explains a wide array of metabolic features of soy-fed rodents: the lower hepatic VLDL secretion, the higher hepatic HMG-CoA reductase activity, the higher hepatic apo B, E receptor activity, the higher fecal bile acid excretion, and finally the lower serum cholesterol concentrations.

Animals↗

The effect of a free mackerel-supplemented diet on plasma and lipoprotein lipid concentrations in normolipidemic subjects.

The effect of mackerel consumption on plasma and lipoprotein lipid concentrations was studied in a seven-day experiment in eight healthy, normolipidemic subjects. Participants ate about 100 g mackerel (corresponding to about 2.5-3 g omega 3 fatty acids daily. The mean triglyceride concentrations in total plasma, VLDL, and LDL were significantly reduced by 40, 46.7, and 38.5% respectively after fish consumption. There was also a small (non-significant) reduction of plasma cholesterol and a (significant) increase of the ratio of HDL/total plasma cholesterol. These data show that a moderately increased intake of omega-3 fatty acids by fish food can change lipid characteristics in healthy normolipidemic individuals within a short-time period, even on a free diet.

Adult↗

Influence of different dietary proteins on plasma growth hormone in rats.

Dietary casein, compared to vegetable protein, causes hypercholesterolemia in some animal species. This may be associated with a change of hormonal status. Among others, GH has an important impact on cholesterol metabolism; GH deficiency results in hypercholesterolemia. This paper shows that the rhythmic variation of GH levels in rats is differently affected by different dietary proteins. Within a 4-h observation period overall mean values and integrated areas under the GH levels plotted against time are higher with casein as compared to soy protein. Secretory GH peak values are lower than reported before for chow-fed rats. These observations support the idea that different dietary proteins cause a different endocrine response. As GH levels are higher with casein, while lower levels would be expected to be associated with hypercholesterolemia, the observed differences are obviously of less relevance for the expression of casein-induced hypercholesterolemia.

Animals↗

Influence of casein versus soy protein isolate on lipid metabolism of minipigs.

This report describes whether a complete exchange of soy protein isolate for casein affects serum lipid or lipoprotein levels. For this purpose, 10 adult minipigs underwent two 6-week crossover experiments, one with 11 and one with 22 weight % protein in a western-style diet. Cholesterol levels were 2.02 +/- 0.06 and 1.98 +/- 0.04 mmol/l with casein and soy, respectively (22 weight %) and 2.08 +/- 0.06 and 2.04 +/- 0.05 mmol/l, respectively (11 weight %). There was a significant rise of high-density lipoprotein cholesterol by the lower protein intake, both with casein and soy. In all experiments nitrogen balance was positive. Soy feeding was accompanied by a significant rise of fecal bacterial protein excretion, as calculated from diaminopimelic acid. In summary, no statistically significant difference of plasma or low-density lipoprotein cholesterol levels were observed, neither due to the kind nor to the amount of dietary protein.

Animals↗

Bile acids inhibit secretion of very low density lipoprotein by rat hepatocytes.

The influence of taurocholate on very low density lipoprotein (VLDL) triacylglycerol synthesis and secretion was studied by isolated rat liver-parenchymal cells. The incorporation of [3H]glycerol into cell-associated and VLDL triacylglycerols were measured after incubation in medium containing 0.75 mM oleate. Taurocholate caused a maked decrease in VLDL [3H]triacylglycerol secretion from the hepatocytes: 50-150 microM taurocholate inhibited secretion of VLDL [3H]triacylglycerols by 70-90%. Similar results were obtained when the mass of secreted VLDL triacylglycerols was measured. Taurocholate caused a decreased secretion of VLDL [3H]triacylglycerols after 15-30 min incubation. A higher amount of cellular triacylglycerols was found in taurocholate-supplemented cells. Furthermore taurocholate did not change the intracellular lipolysis of triacylglycerols. These results suggest that bile acids interfere more probably with the assembly and/or secretion of VLDL-particles and not with earlier stages of VLDL formation, e.g. triacylglycerol synthesis.

Animals↗

Oral intake of glucose plus galactose and erythrocyte galactose-1-phosphate. A nutritional evaluation of hydrolyzed lactose.

This study deals with the metabolic effects of hydrolyzed lactose: After an overnight fast 5 healthy adult volunteers consumed a glucose-galactose mixture equivalent to 61.4 g of lactose (or 125 g of a dried skim milk powder with hydrolyzed lactose). The postprandial rise of erythrocyte galactose-1-phosphate (gal-1-P) never exceeded 22.3 mumol per liter packed red blood cells. This amounts to no more than 22% of the levels known from galactosemic children to be safe, concerning ocular, neural or hepatic damage. We conclude that the consumption of the hydrolyzed lactose does not cause a risk for consumer's health as judged from this galactose metabolite. A considerably higher risk, however, may accompany the consumption of galactose alone which causes around 17-fold higher plasma galactose levels and around 8-fold higher erythrocyte gal-1-P concentrations for more extended time periods.

Adult↗

Effects of oral and intracecal pectin administration on blood lipids in minipigs.

The effects on blood lipids of oral and intracecal pectin administration for 4 wk were examined in six male adult hypercholesterolemic minipigs (total serum cholesterol = 8.4 mmol/L. The pigs were fitted with a cecal cannula and were assigned to three groups of two pigs each; the groups underwent an experiment in 3 X 3 Latin square design. The control period was designated as that during which water was infused into the cecum. Total serum cholesterol concentration was about 50% lower after feeding 75 g pectin per day than during the control period. The intracecal infusion of the same amount of pectin had no effect on total serum cholesterol concentration compared to the control period. The cholesterol level in the low density lipoproteins (LDL), in the very low density lipoproteins (VLDL) and in the high density lipoproteins (HDL) was lower after feeding pectin than in the control period. The HDL cholesterol, but not LDL or VLDL cholesterol, was at a lower level after intracecal infusion of pectin than during the control period. Thus, the study clearly demonstrates that the passage of pectin through the small intestine is necessary for its hypocholesterolemic action.

Administration, Oral↗

Modulation of very low-density lipoprotein secretion by dietary protein is age-dependent in rats.

The Triton WR-1339 technique was used in order to study age-dependent changes of the rate of very low-density lipoprotein (VLDL) lipid secretion in rats consuming either casein or soy protein isolate. There was a significantly higher influx of lipoprotein cholesterol and triglycerides into the plasma compartment (of fasted animals) after a casein than after a soy diet, both in 10-week-old animals (cholesterol: 0.78 +/- 0.06 vs. 0.52 +/- 0.03 mmol X 1(-1) X h-1) and 25-week-old animals (cholesterol: 0.50 +/- 0.07 vs. 0.32 +/- 0.05 mmol X 1(-1) X h-1), but secretion rates diminished with age. The higher secretion rates following casein were paralleled by higher serum cholesterol levels in the fasted younger animals and also, though to a lesser degree, in the fed animals. These data contribute further evidence to our earlier proposal that dietary protein may induce different serum lipid levels by the modulating rate of lipid influx into the plasma compartment.

Aging↗

Influence of dietary casein and soy protein isolate on intestinal cholesterol and bile acid concentration.

This study reports quantitative and qualitative differences in intestinal bile acids and cholesterol in miniature pigs following dietary casein or soy protein isolate. The total amount of bile acids in the small intestine was significantly higher when soy protein isolate was fed in comparison to casein. The values were (mean +/- SEM) 4.51 +/- 0.39 mmol and 2.43 +/- 0.08 mmol, respectively, when the proteins were given as the sole component of the diet. When the proteins were given as part of a semi-purified diet, these values were 6.44 +/- 1.04 mmol and 3.95 +/- 0.39 mmol, respectively. Hyocholic acid amounted to 39.6%, hyodeoxycholic acid to 31%, and chenodeoxycholic acid to 27.6% of total bile acids in the small intestine when casein was fed. The soy-fed animals tended to have more secondary bile acids. The total small bowel chymus content, on a wet weight basis, was 63% higher in the soy group. In all experimental conditions studied, there was a close correlation between small bowel chyme content and bile acid content. The distribution of bile acids in the small intestine showed that the soy fed animals tended to have more bile acids in the distal parts of the jejunum. The intestinal cholesterol contents were not significantly different between dietary groups.

Animals↗

Influence of hormones and growth factors on viability, DNA, and protein content of adult hepatocytes in primary culture.

The survival of adult rat hepatocytes in monolayer culture was studied in the presence of different hormones (neurotensin, oxytocin, thyrotropin releasing hormone, luteinizing hormone releasing hormone, cholecalciferol, bradykinin, substance P, aldosterone, melanocyte stimulating hormone, 3,3',5-triiodo-1-thyronine, corticosterone, human growth hormone, glucagon, insulin, progesterone, testosterone, estradiol, and dexamethasone phosphate) or growth factors (fetal bovine serum). For this purpose trypan blue exclusion, lactate dehydrogenase, and DNA and protein content were measured at 24 and 72 h of culture. 10(-7) M Dexamethasone, a mixture of eight hormones, 10% fetal bovine serum, and a combination of the latter two supplements caused a more than 64% higher DNA content at 72 h when compared to control cultures. A striking agreement of these results with changes of lactate dehydrogenase leakage was observed, whereas trypan blue exclusion gave erratic results. Considerable changes of cell arrangement apparently specific for each supplement were observed by low magnification microscopy. It is concluded that glucocorticoids and fetal bovine serum have an outstanding effect on cell viability and that DNA or protein content or both are reliable indicators of cell viability in amitotic cultures.

Animals↗

Influence of lysine on urea cycle activity and orotate formation in the isolated perfused rat liver.

There was a reversible inhibition of urea formation in the perfused rat liver caused by 2.25-27 mM lysine acting with a Ki of 10.8 mM in competition with ornithine. Urea formation in the presence of inhibitory concentrations of lysine ranged between 2.3 and 2.9 mumol X min-1 X (g, liver wet)-1 after addition of 1 mM of citrulline, argininosuccinate or arginine, whereas it amounted to 0.5 mumol X min-1 X (g, liver wet)-1 after addition of ornithine, showing that lysine inhibited the urea cycle between ornithine and citrulline. There was a rise of basal orotate formation of 0.03 +/- 0.02 mumol X h-1 X (g, liver wet)-1 towards a maximum of 0.6 +/- 0.04 mumol X h-1 X (g, liver wet)-1 after addition of 13.5 mM lysine, provided orotate utilization was blocked with allopurinol. Maximal rates of orotate formation were reached when ammonium concentrations exceeded 1 mM. We conclude that an inhibition of urea synthesis and a rise of orotate formation are caused by lysine in the isolated liver in vitro at rates observed in vivo. Hence, these metabolic alterations observed in the whole animal are most probably due to changes of liver metabolism.

Ammonia↗

Influence of dietary casein or soy protein on serum lipids and lipoproteins of monkeys (Macaca fascicularis).

In order to learn whether a complete exchange of dietary soy protein for casein causes a change of serum lipid levels in primates, 8 Macaca fascicularis monkeys were fed a semi-purified ration; its basic composition was similar to diets consumed in Western Europe. In a crossover experiment, casein was exchanged for a soy protein isolate and vice versa. Plasma and lipoprotein cholesterol and triglyceride levels were determined following a 3-week dietary regimen. There was no significant difference of total serum cholesterol levels between the soy protein and casein periods (4.6 vs. 4.7 mmol/l). However, high-density lipoprotein (HDL) cholesterol levels were significantly higher (1.6 vs. 1.2 mmol/l, p less than 0.01) and very-low-density lipoprotein (VLDL) cholesterol levels were significantly lower (0.39 vs. 0.55 mmol/l, p less than 0.01) following the soy protein diet. There was no distinct change in total or lipoprotein triglyceride levels following exchange of the dietary protein. It is concluded that in nonhuman primates a complete exchange of soy protein for casein produces changes of HDL, but not of total or low-density lipoprotein (LDL) cholesterol.

Animals↗

Regulation and interaction of cholesterol, bile salt and lipoprotein synthesis in liver.

The liver is the junction of several inter-organ metabolic cycles which are essential for the homeostasis of mammalian metabolism. Two of these are described in greater detail and their role in control of lipid metabolism will be presented. The fatty acid-triglyceride cycle is of particular importance for our understanding of the mechanisms governing serum lipid levels. This is due to the fact that the lipoprotein secreted by the liver in the course of this metabolic cycle - very low density lipoprotein - has a relatively long half-life in the plasma compartment. Data have been collected from the literature to show that different nutritional and pharmacological stimuli affecting serum lipid levels do so by interfering with the rate of very low density lipoprotein input into the plasma compartment. The enterohepatic circulation of steroids is another cycle which contributes to control of lipid metabolism. Data are presented which show that bile acids, the major steroids circulating in this cycle, exert direct feedback control of hepatic cholesterol synthesis. This characteristic of bile acids may explain why certain bile acids, when given orally, reduce serum cholesterol levels. Several clinical and experimental observations suggest a close relation between bile acid and triglyceride metabolism. It is characterized by an inverse relation between bile acid pool size and serum triglyceride levels. Moreover, a reduction of the bile acid pool size is accompanied by an enhanced hepatic fatty acid and triglyceride synthesis and secretion into blood. The molecular basis and physiological significance of these observations have still to be explored.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile Acids and Salts↗

Regulation of lipogenic enzymes in human diploid fibroblasts by hormones.

The hormonal regulation of two regulatory enzymes of fatty acid synthesis acetyl-CoA carboxylase (EC 6.4.1.2) and glucose-6-phosphate dehydrogenase (EC 1.1.1.49), has been investigated in human diploid fibroblasts. There was a 35% increase in acetyl-CoA carboxylase activity, 72 h following addition of 10 microU/ml insulin to the culture medium. Addition of 1 microgram/ml of 3,3'5-triiodothyronine for 72 h resulted in an increase in acetyl-CoA carboxylase activity to 166% of the controls. The simultaneous addition of 1 microgram/ml triiodothyronine and 10 mU/ml insulin caused the enzyme activity to rise to 240% of the controls. A dose-dependent reduction in acetyl-CoA carboxylase activity was brought about by 1 X 10(-4) to 1 X 10(-3) M dibutyryl cyclic AMP. The earliest effect of dibutyryl cyclic AMP was observed within 24 h. Glucose-6-phosphate dehydrogenase followed qualitatively the same pattern of response, whereas the constitutive enzyme, lactate dehydrogenase (EC 1.1.1.27), did not show significant changes in these experiments. The data demonstrate common features of hormonal regulation of lipogenesis in human fibroblasts with liver and adipose tissue and substantiate the growing evidence that thyroid hormones are of major importance for the regulation of this process.

Acetyl-CoA Carboxylase↗

Influence of fatty acids on cholesterol synthesis of hepatocytes in monolayer culture.

The short-term (6-hour) and long-term (72-hour) influences of a wide spectrum of fatty acids on cholesterogenesis in monolayer cultures of rat hepatocytes were studied. A 6-hour addition of 0.5 mmol/liter of oleate to the culture medium raised 3-hydroxy-3-methylglutaryl-CoA reductase [mevalonate:NADP+ oxidoreductase (CoA-acylating), EC 1.1.1.34] activity by 62%. Octanoate, palmitate, stearate, linoleate, arachidonate and linolenate did not change enzyme activity significantly under these circumstances. A 72-hour incubation led to a 162% rise of enzyme activity by oleate and a 33% lowering by arachidonate, the other long-chain fatty acids having no significant effect (linoleate, linolenate, palmitate and stearate). These modulations of enzyme activity were paralleled by comparable changes of cholesterogenesis as measured by incorporation of [1-14C]acetate into cholesterol. The results are compatible with the concept that the response of hepatic cholesterogenesis to dietary triglycerides in vivo (observed by earlier investigators) is due to influences of the triglyceride fatty acids on hepatocyte 3-hydroxy-3-methylglutaryl-CoA reductase activity.

Acetates↗

Hormonal regulation of lipogenesis in human diploid fibroblasts from normal subjects and from patients with familial hypertriglyceridaemia.

Lipogenesis has been investigated in diploid fibroblasts derived from patients with familial hypertriglyceridaemia (FHT) and compared with cells from healthy persons. There was no difference in acetyl-CoA carboxylase activity in both cell types. Incorporation of [2-14C]-acetate into triglyceride fatty acids was slightly increased (34%) by the FHT lines. Addition of triiodothyronine caused a marked rise in [2-14C]-acetate incorporation by the FHT lines whereas the normal lines exhibited only control values. Maximal rise in [2-14C]-acetate incorporation was obtained with 5 micrograms/ml for 72 h. Under these conditions, acetate incorporation by the FHT lines was 220% of the controls, compared with 94% by the normal lines. Measurements of acetyl-CoA carboxylase specific activity supported the results obtained with measurements of acetate incorporation into triglyceride fatty acids. Individual FHT lines differ much in their quantitative answer to thyroid hormones, although the described effects were obtained with all eight lines under study. Insulin increased acetyl-CoA carboxylase activity and incorporation of [2-14C]-acetate in lipids in both cell types, but with no difference between normal and FHT lines. The results seem to reflect a higher lipogenic capacity of the hypertriglyceridaemic fibroblasts compared with normal cells.

Acetates↗