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Expression of mutant bovine growth hormone genes in mice perturbs age-related nutrient utilization patterns.

Three lines of transgenic mice expressing mutant bovine growth hormone (bGH) genes and displaying small (G119K), near normal (M11) or large (M4) phenotypes and nontransgenic control (NTC) mice were used to determine GH-associated, age-specific changes in empty body composition. The single amino acid substitution in G119K mice reduced the quantities (P < 0.001) and early rates (P < 0.05) of deposition for water, protein and ash but resulted in similar quantities of fat as the NTC mice. The change in relative quantities of empty body components indicated the G119K analogue altered nutrient partitioning, basal metabolism and (or) nutrient availability to effect the differential observed in body composition. The two amino acid substitutions in the bGH gene expressed by the M11 mice caused only a small change in phenotype, but age-related changes in the accretion of protein, fat and ash indicated these mice were not mature by 68 d of age. The bGH analogue produced by the M4 mice resulted in a doubling (P < 0.001) of body weight in comparison with the NTC mice, a result of the increasing (P < 0.001) rate of weight gain. Empty body component gain of the M4 mice also indicated they had not yet matured by 68 d of age. The G119K and M4 mutant forms of bGH altered rates and composition of growth, possibly through redirection of tissue nutrient utilization, modification of nutrient metabolism, and(or) nutrient availability.

Aging↗

Investigation into the occurrence and structure of lectin receptors on human and bovine erythrocytes milk fat globule and lymphocyte plasma-membrane glycoproteins.

The reduced disaccharide beta-D-galactosyl(1-3)-N-acetyl-D-galactosaminitol was released, after alkaline borohydride and neuraminidase treatment, from human and bovine erythrocyte membrane and fat globule membrane glycoproteins as well as from human and bovine lymphocyte plasma membranes. This disaccharide was found to be substituted to different extents by sialic acid in the various fractions. beta-D-Galactosyl(1-3)-N-acetyl-D-galactosamine is the immunodominant disaccharide of the Thomsen-Friedenreich antigen (TF) and was detected serologically using specific lectins and antibody-containing sera. Bovine fat globule membrane glycoproteins were the only source of Tn antigen. The Tn antigen was detected by anti-Tn-containing sera and by the lectins from Salvia sclarea and Helix pomatiea as well as gas chromatographic detection of N-acetylgalactosaminitol after alkaline borohydride treatment of the native glycoproteins. Human milk fat globule membrane glycoproteins showed the presence of blood group A substance by reaction with rabbit anti-A serum.

ABO Blood-Group System↗

Effects of alcohol ingestion on lipids and lipoproteins in normal men: isocaloric metabolic studies.

To investigate metabolic relationships between alcohol ingestion and fasting plasma high density lipoprotein cholesterol (C-HDL) and triglycerides, seven young normal males were assessed with isocaloric substitution of alcohol for carbohydrate in the diet. For a 5-week study period, an isocaloric low cholesterol diet containing 20% of the calories as protein, 40% as fat, and 40% as carbohydrate, with < 300 mg cholesterol per day, P/S 1.5/1, was ingested. In weeks 2 and 3, 35 and 53 g/day of 100 proof Vodka were ingested, with isocaloric substitution of alcohol for dietary carbohydrate during these study weeks. In week 5, 1.35 g/day of lecithin linoleate was added to assess another putative nutritional approach to increasing C-HDL levels. By two-way analysis of variance and Scheffe's paired t tests, there were no significant differences in either C-HDL or triglyceride levels for any of the five metabolic diet, alcohol substitution diet periods; additionally, there were no significant effects of lecithin on plasma lipids or lipoproteins. The general question asked, "Does alcohol affect C-HDL levels?" is answered negatively for isocaloric alcohol substitution, on a cholesterol-poor, high P/S, and relatively carbohydrate restricted diet, for a 2-week period of moderate alcohol intake. Alcohol's effect on C-HDL and triglyceride probably involves an interaction with total calories, and perhaps with dietary composition (cholesterol, saturated fat, carbohydrate content), as well as the amount of ethanol ingested, and duration of intake.

Adolescent↗

First data on background levels of non-ortho and mono-ortho PCBs in blood of residents from southern Germany.

Blood-fat concentrations of polychlorinated biphenyls (PCB) congeners: no. 105, 118, 156 (mono-ortho-substituted) and no. 77, 126, 169 (non-ortho-substituted) and PCB congeners no. 28, 52, 101, 138, 153 and 180 were measured. The investigations were carried out in pooled samples from children and in individual samples from adults. Additionally polychloro-p-dibenzodioxins and -furans (PCDD/PCDF) were investigated.

Adipose Tissue↗

[MR-tomography and -spectroscopy of skeletal muscles using high magnetic field strengths].

Intact as well as neuromuscular affected skeletal muscles can be precisely analysed by MR tomography with high magnetic field strengths. The substitution of muscle by adipose tissue under atrophic conditions is seen most clearly in fat images, while the morphology of small structures is predominantly shown by water images. The aim of in-vivo spectroscopy is an identification and quantification of metabolites. A relative increase in the amount of adipose tissue within atrophic muscles was confirmed by the 1-H spectrum. As concluded from 13-C and 31-P spectra there was neither a change in adipose tissue composition nor a modification of energy metabolism.

Adenosine Triphosphate↗

Fats and fatty acids as growth factors for Lactobacillus delbrueckii.

The effects of various fats and fatty acids on the growth of Lactobacillus delbrueckii strains have been studied using modified MRS broth without Tween 80 as a basic growth medium. Among the six L. delbrueckii strains studied all except one strain required Tween 80 or Tween 20 as a fatty acid supplement for the growth. Tween 40 and Tween 60, which contain solely medium and long chain saturated fatty acids, inhibited the growth of all L. delbrueckii strains when present as a sole fat supplement in MRS broth. Free oleic acid but not free lauric acid could substitute Tween 80 or Tween 20 supplement suggesting that unsaturated fatty acids are essential growth factors for most L. delbrueckii strains. Among the natural food oils tested, the oils containing the lowest amounts of saturated long chain fatty acids promoted the growth of L. delbrueckii most effectively. Especially cellular C18:1 and C19 cyclopropane fatty acid contents of L. delbrueckii were strongly affected by exogenous fatty acid composition and by strain suggesting genetic diversity and polymorphism among the genes encoding and/or regulating cyclopropane synthase. In addition obviously most if not all L. delbrueckii strains lack particular synthase, desaturase and/or dehydrase activities required for de novo synthesis of long chain unsaturated fatty acids. These biochemical features could be used as informative chemotaxonomic characteristics for L. delbrueckii starter strain identification and selection.

Fatty Acids↗

Increased plasma clearance rate of thyroxine despite decreased 5'-monodeiodination: study with a peroxisome proliferator in the rat.

In euthyroid rats a 17-day treatment with nafenopin, a hypolipidemic agent and peroxisome proliferator, decreased serum total and free T4 concentrations to 32 +/- 5% and 62 +/- 8% (mean +/- SEM; n = 10), respectively, with no change in serum T3 and TSH concentrations. In methimazole-treated rats infused with 3 nmol T4/day/100 g BW, the nafenopin inhibitory effect was not significantly different from that in euthyroid rats. Nafenopin treatment had the following effects on peripheral T4 and T3 metabolism in euthyroid rats. The plasma clearance rate of T4 (PCR), which was measured by Alzet minipump infusion of tracer, was increased 2-fold (1.58 +/- 0.09 vs. 0.82 +/- 0.06 ml/h.100 g BW; P less than 0.001; n = 5), while the PCR of T3 was decreased (37.5 +/- 1.3 vs. 53.8 +/- 1.8; P less than 0.001; n = 5). The fecal clearance rate of radioactivity derived from T4 was increased 2-fold (1.93 +/- 0.10 vs. 0.77 +/- 0.07 ml/h.100 g BW), whereas the urinary clearance rate was not significantly modified. The 5'-deiodinase (5'D) activity, measured by deiodination of labeled rT3, was strongly inhibited in liver and kidney, not modified in brown fat and anterior pituitary, and increased in cerebral cortex. In methimazole-treated rats substituted with isopropyl-diiodothyronine only hepatic 5'D activity was decreased. It is concluded that the decrease in serum total and free T4, without alteration in serum T3 and TSH concentrations, resulting from nafenopin treatment is mainly due to changes in peripheral T4 and T3 metabolism, since it is also observed in T4-substituted animals. The increased PCR of T4 cannot be explained by an increase in deiodination activity, since the major 5'D pathways are inhibited after nafenopin treatment, and the urinary clearance rate is not modified. It can partly be explained by an increase in the fecal clearance rate of T4, which could be due to an increase in glucoronoconjugation. In addition, nafenopin was found to be a weak competitor of T4 binding to serum proteins, leading to a small increase in the free T4 fraction which might also contribute to the increased T4 PCR. The decrease in T3 PCR remains to be explained.

Adipose Tissue, Brown↗

[Supplementation of wheat flour with chickpea (Cicer arietinum) flour. I. Preparation of flours and their properties for bread making].

The feasibility of adding chick-pea flour substituting part of wheat flour in yeast-leavened bread-making in order to increase the protein value, was studied. A 70% extraction chick-pea flour of commercial granulometry (150 mu) was prepared. Wheat flours of 74% and 78% extraction were then blended with 5%, 10% and 15% of chick-pea flour. Every flour and blend were subsequently analyzed to determine protein, ash, fiber, fat and maltose content, as well as sedimentation, farinogram and bread-making. Addition of chick-pea flour increased protein, fiber, ash and fat content in the blends, not causing a severe effect on quality, even at the 15% level of substitution. Blends showed an increase in maltose content, W value and bread specific volume. Furthermore, breads prepared were of good quality even without the use of maturing agents.

Bread↗

Effect of 347-serine mutation in apoprotein A-IV on plasma LDL cholesterol response to dietary fat.

Lipid response to dietary fat and cholesterol is, to a large extent, genetically controlled. Apoprotein (apo) A-IV has been related to fat absorption and to the activation of some of the enzymes involved in lipid metabolism. One mutation has been described in the apo A-IV gene that causes substitution of Ser for Thr at position 347. To study the influence of this mutation on the plasma LDL cholesterol (LDL-C) response in diets of various fat content and fatty acid saturation, 41 healthy male subjects were studied, 25 of whom were homozygous for the Thr allele (347Thr) and the rest who were either homozygous (n = 2) or heterozygous carriers of the Ser allele (347Ser). They consumed three consecutive diets, each of 4 weeks' duration: one rich in saturated fat (SFA diet: 38% fat, 20% saturated), a National Cholesterol Education Program (NCEP) type 1 diet (28% fat, 10% saturated), and a third rich in monounsaturated fat (MUFA diet; 38% fat, 22% monounsaturated). Carriers of the 347Ser allele presented a greater decrease in total cholesterol (-0.7 vs -0.44 mmol/L, P < .034), LDL-C (-0.62 vs -0.31 mmol/L, P < .012), and apo B (-14 vs -8 mg/dL, P < .01) levels when they were switched from the SFA to the NCEP type 1 diet than homozygous carriers of the 347Thr allele. The change from the NCEP type 1 to the MUFA diet resulted in a greater increase in total cholesterol (0.18 vs -0.05 mmol/L, P < .028) and apo B (5 vs -1 mg/dL, P < .006) levels in the 347Ser than in the 347Thr individuals. In a previous study, we demonstrated that the G-->A polymorphism at position -76 of the gene promoter of apo A-I affects the LDL-C response to dietary fat. We therefore decided to study the effect of the interaction between these mutations on this response. We found that both mutations have an additive effect on total cholesterol, LDL-C, and apo B dietary-induced changes. Our results suggest that total cholesterol and LDL-C response to dietary fat is influenced by the 347Ser mutation of apo A-IV.

Adult↗

No effect of oral or sample temperature on sensory assessment of fat content.

This work examined the possible influences of oral and sample temperature on the perception of fat content of a model food system. Melting or related phenomena may contribute to the greater sensation of fat content and the highly acceptable textural characteristics associated with certain fats. Thirty-one adults assessed the fat content of 0%, 12%, 24%, 36%, and 48% oil-in-water emulsions prepared with a commercial cocoa butter substitute having a melting range of 17-41 degrees C. Samples were evaluated at combinations of sample and mouth temperatures of 20 and 36 degrees C, with oral temperatures manipulated by repeated cold- and warm-water rinses prior to assessments. There were no significant differences amongst these treatments on perceived fat content of the samples, nor were subject characteristics of age or body composition related to judgments of fat content in these stimuli. Although previous studies had shown that degree of fat saturation is associated with enhanced perception of fat content (11), that does not appear to be related to the degree or occurrence of melting in the mouth over the ranges studies here.

Adolescent↗

Influence of substitution method and of food intake on bioassays to determine metabolisable energy with chickens.

Several different methods of assaying the metabolisable energy (ME) of ground maize and a maize and glucose mixture were studied. Over a 24-h period fasted cockerels lost more energy and nitrogen in their excreta than those fed 15 g maize and 15 g glucose monohydrate. Discrepancies in ME values of maize were found between 1) Hill's method (substitution for glucose) and 2) Sibbald's method (the difference between energy ingested and excreted, corrected for endogenous losses by a comparison with fasted controls). These discrepancies were attributed to differences in endogenous energy losses between fed and fasted birds and interactions between the test substance and reference diet. No significant differences could be detected when substitution for glucose was compared to substitution for the entire diet in three experiments. Significant differences in the ME of maize because of the composition of the basal diet were found (semi-purified:practical; 17.20: 14.56 kJ/g; and 50 g/kg added fat: 100 g/kg added fat; 15.94: 16.69 kJ/g). Food intakes equal to 70, 60 or 30% of ad libitum did not affect the ME of maize when the substitution for glucose method was used. It is concluded that basal diets for ME determinations should be carefully selected because of possible interactions between dietary components. When ME is determined by feeding small amounts of the test material, endogenous losses may be over-estimated because the control birds are in a different physiological state (fasted).

Animal Feed↗

Bioisosterism in drug design: identification of and structure-activity relationships in a series of glycine anilide ACAT inhibitors.

To examine the effects of bioisosteric replacement on the biological activity of our previously disclosed disubstituted urea inhibitors of the enzyme acyl-CoA:cholesterol acyltransferase (ACAT), we prepared a series of N'-substituted and N',N'-disubstituted glycine anilides. These compounds were tested for the ability to inhibit ACAT in vitro and lower plasma total cholesterol in cholesterol-fed rats given a single high-fat, high-cholesterol meal. ACAT inhibitory potency was greatest in compounds containing 2,6-diisopropyl substituents in the anilide portion with the glycine nitrogen substituted by a 1,1-diphenylmethyl moiety. Small improvements in potency in vitro were obtained by substitution of electron donating groups in the 2-, 3- or 5-positions of the aryl rings of the 1,1-diphenylmethyl moiety, but not by substitution in the 4-position. In vitro potency was maintained, but not improved by acylation of the glycine nitrogen. Through a QSAR analysis of in vitro ACAT inhibition for this set of compounds, an equation could be derived which accounted for 85% of the variance in the dataset. An optimal clogp of 6.65 was found, comparable to that found for other series of ACAT inhibitors. In general, compounds from this series displayed inhibitory potency against ACAT in vitro and hypocholesterolemic activity in the in vivo rat model of hypercholesterolemia comparable to that found with the ureas.

Acyl Coenzyme A↗

Serum lipid response to oat product intake with a fat-modified diet.

Healthy adult volunteers (no. = 208), men and women aged 30 to 65 years, participated in a 12-week study on dietary fat modification plus oat product ingestion (60 gm/day) to test whether moderate daily intake of oat bran and oatmeal enhanced serum lipid response. During weeks 0 to 6, all participants followed the American Heart Association fat-modified eating style. At 6 weeks, participants were randomly assigned to one of three groups. All participants continued to follow the fat-modified eating pattern; groups 1 and 2 were asked during weeks 7 to 12 to consume two servings of either oat bran or oatmeal per day, for a total of 60 gm/day isocalorically substituted for other carbohydrates. Group 3 ingested no oat products. At baseline, the group mean cholesterol level was 208.4 mg/dl. After 6 weeks of dietary fat intervention, the level was 197.6--a fall of 10.8 mg/dl (5.2%). At 12 weeks, the mean serum cholesterol level fell further, by 5.6, 6.5, and 1.2 mg/dl for groups 1, 2, and 3, respectively. Group mean weight loss was small--1.9 lb during the first 6 weeks and 0.6 to 0.8 for the three groups during weeks 7 to 12. Reported oat product ingestion was 39 and 35 gm per person per day, respectively, for groups 1 and 2 (2.2 and 1.4 servings per person per day, respectively). Dietary fat composition remained similar among the three groups during weeks 7 to 12. Pooled results indicated that the addition of oat products at a moderate and practical level enhanced serum lipid response (p less than .05) to a fat-modified eating pattern among free-living adults.

Adult↗