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Effect of dietary fat on chronic ethanol-induced oxidative stress in hepatocytes.

BACKGROUND: Although oxidative stress and deficits in hepatic energy metabolism have been implicated as important factors in the initiation of alcoholic liver disease, their relative contribution to ethanol-induced cell death is not known. The purpose of this study was to examine the effects of chronic ethanol administration on hepatocyte reactive oxygen species (ROS) generation, energy state, and viability, as well as the effect of dietary fat on these parameters. METHODS: Male Sprague-Dawley rats were fed liquid diets that provided 36% total calories as ethanol, with fat as either 12% (low fat) or 35% (high fat) of total calories. Pair-fed controls received liquid diets in which maltose-dextrin was substituted for ethanol calories. The fluorescent probe 2',7'-dichlorofluorescin diacetate was used to detect ROS, lactate dehydrogenase leakage was used to assess viability, and ATP levels were used as a measure of the energy state. The effect of chronic ethanol feeding on these parameters was determined by incubating hepatocytes under a 5% oxygen-containing atmosphere or an atmosphere < or = 1% oxygen for 60 min. RESULTS: In general, chronic ethanol feeding stimulated ROS production and decreased ATP concentrations, which were associated with decreased viability in hepatocytes isolated from rats fed either high- or low-fat, ethanol-containing diets, compared to the corresponding controls. Incubation under an atmosphere < or = 1% oxygen and/or ethanol (10 mM) augmented these effects in both high- and low-fat control and ethanol-fed hepatocytes. The addition of antimycin to the incubations increased ROS production, decreased ATP concentrations, and accelerated loss of hepatocyte viability. Viability loss under all conditions used in this study was correlated with decreases in cellular ATP. CONCLUSIONS: Comparisons of incubations performed under the two oxygenation conditions revealed that viability loss was inversely associated with ROS production, which indicates that ATP loss and not ROS production was a better predictor of loss in cell integrity. This study also demonstrates that the level of dietary fat has only minor effects on generation of ROS and the cellular energy state. In contrast, ethanol consumption had significant effects on generation of ROS, energy state, and hepatocyte viability.

Adenosine Triphosphate↗

Inhibitory effects of chondroitin sulfate prepared from salmon nasal cartilage on fat storage in mice fed a high-fat diet.

OBJECTIVE: Chondroitin sulfate is an acidic polymer consisting of repeating D-glucuronic acid and D-N-acetylgalactosamine units, and the N-acetylgalactosamine is substituted with the sulfate at either the 4' or 6' position, with approximately one sulfate being present per disaccharide unit. The present study assessed the effects of chondroitin sulfate on the activity of pancreatic lipase and lipid uptake into brush border membrane vesicles of the rat small intestine in vitro, and on the degree of fat storage induced in mice by the oral administration of a high-fat diet for 8 weeks. DESIGN AND MEASUREMENTS: Experiments were carried out to clarify whether or not chondroitin sulfate inhibited pancreatic lipase activity in assay systems using triolein emulsified with phosphatidylcholine or gum arabic. In addition, the effects of chondroitin sulfate on lipid absorption by brush border membrane vesicles were examined. Moreover, mice were fed a high-fat diet and treated with chondroitin sulfate for 8 weeks. RESULTS: Chondroitin sulfate dose-dependently inhibited the pancreatic lipase activity in an assay system using triolein emulsified with phosphatidylcholine. In addition, chondroitin sulfate inhibited the palmitic acid uptake into the brush border membrane vesicles of the rat jejunum. Chondroitin sulfate caused the reduction of body weight and parametrial adipose tissue weight, and prevention of fatty liver and hyperlipidemia in mice fed a high-fat diet. CONCLUSION: The reduction of fat storage and the antihyperlipidemic action of chondroitin sulfate might be due to the inhibition of small intestinal absorption of dietary fat through the inhibition of pancreatic lipase activity and fatty acid uptake through brush border membrane.

Adipose Tissue↗

Regulation of blood glucose level in diabetes mellitus using palatable diet composition.

Diabetes mellitus results from the failure of the endocrine system to control the blood glucose levels within the normal limits. Normal people have fasting sugar level that generally run between 70-110 mg/dl, while a person is said to suffer from diabetes if the blood glucose level in the interval of 2 hours equals to or exceeds 180 mg/dl. It can be understood as a disorder of carbohydrate metabolism and characterized primarily by hyperglycemia and glycosuria with second anomalies of the metabolism of protein and fat. It is not only the leading cause of blindness, renal failure and non-traumatic amputations in adults but also a major cardiovascular risk factor in developing countries. So, it is of great interest to propose a palatable composition of quantitative diet for the human beings suffering from Diabetes Mellitus to regulate the blood glucose and insulin level. In the present study, the palatable composition is calculated by two mathematical models and given in the form of calories for protein (P), fat (F) and carbohydrate (C). For the calculations, the mixed population has been distinguished into three categories namely men, women and juvenile having various body frames i.e. small, medium and large. With the substitution of this composition in the solutions, the near-normal level of blood glucose and insulin is achieved. Hence, a plausible palatable composition of protein, fat and carbohydrate has been proposed which can be incorporated in diet for the significant regulation of blood glucose and insulin level in diabetic patients.

Adolescent↗

Long-term metabolic consequences of switching from protease inhibitors to efavirenz in therapy for human immunodeficiency virus-infected patients with lipoatrophy.

The roles of nucleoside analogues and protease inhibitors (PIs) in the development of metabolic complications and fat-distribution abnormalities associated with highly active antiretroviral therapy (HAART) are not well known. We performed an observational study in which efavirenz was substituted for a PI for 41 patients receiving HAART who had prolonged virus suppression, clinical signs of severe lipoatrophy, hyperlipidemia, and insulin resistance. Clinical follow-up was performed for 1 year. Virus suppression was maintained in most of the patients, and a significant increase in CD4(+) lymphocyte count was observed, but no change in lipid profile or insulin resistance was observed. Abdominal fat content did not change, and subcutaneous fat depletion was even more pronounced >1 year after the switch. We conclude that, for PI-treated patients who present with lipoatrophy, hyperlipidemia, and insulin resistance, substituting efavirenz for PIs can maintain virus suppression and immunologic response to HAART, but it does not improve the lipid profile or resolve insulin resistance or lipoatrophy.

Adult↗

Diabetes and nutrition: the mitochondrial part.

Diabetes mellitus is the most common genetic disease in the Western world today. It is the phenotype for >150 genotypes. Each of these genotypes is characterized by impaired glucose tolerance and impaired control of intermediary metabolism. There are many strains of mice and rats that can be used to study diabetes in its various forms. One of these is the BHE/Cdb rat, which mimics the human phenotype with a mutation in the mitochondrial (mt) DNA. The result of such mutation is a loss in metabolic control with respect to the role of the mitochondria in this control. This review addresses those aspects of control that are exerted by mt oxidative phosphorylation (OXPHOS). Diet can have both genomic and nongenomic effects on OXPHOS. The type of dietary fat influences the fluidity of the mt membranes and hence, mt function. The dietary fat effect depends on the genetic background of the consumer. Diabetes-prone BHE/Cdb rats with base substitutions in the mt ATPase 6 gene are more likely to be influenced by the diet effect on mt membrane fluidity than are normal rats. Vitamin A also affects mt function through an effect on mt gene expression. BHE/Cdb rats have a greater need for vitamin A than normal rats and supplemental vitamin A appears to influence OXPHOS.

Adenosine Triphosphatases↗

Ito cell activation induced by chronic ethanol feeding in the presence of different dietary fats.

Bronfenmajer et al. (1966) first studied Ito cells in alcoholic hepatitis (AH) by light microscopy (LM). The number of Ito cells and the number of fat droplets were increased. Okanoue et al. (1983) found that Ito cells were reduced by LM but increased by electron microscopy (EM) in scars in AH. Ito cells were activated in scars (increased RER and decreased fat in Ito cells with transition to fibroblasts). Minato et al. (1983) showed that increased RER in Ito cells correlated with increased collagen synthesis of liver biopsies in vitro. Mak et al. showed increased RER correlated with the degree of fibrosis in alcoholic baboons (1984) and alcoholic cirrhosis in man (1988). French et al. (1988b) showed morphometrically that Ito cell fat was decreased and RER was increased only in scars but not in normal sinusoids so that Ito cell activation was restricted to the scars. There was no correlation of sinusoidally located Ito cell fat or RER with the amount of perisinusoidal collagen. In rats fed ethanol and a nutritionally adequate diet including corn oil (25% of calories) by intragastric cannula for five months the fatty liver progressed to focal central fibrosis, and Ito cell activation (fat/RER) was increased. When tallow was substituted for corn oil the Ito cells were not activated and the liver histology was normal. Thus, the type of dietary fat and the local environment (scars) are important factors in the activation of Ito cells by alcohol in vivo.

Alcoholism↗

Exocrine pancreatic secretion in suckling goats. Adaptative effects of maternal milk and a milk substitute.

Suckling goats were fed ad libitum during the first month of their life by goat milk or by a milk replacer. These diets differed in the amount of fat and the type of protein. The composition of the exocrine pancreatic secretion in the basal period and in response to food were compared in both conditions. Pancreatic juice was collected one hour before meal intake up to the 8th postprandial hour. Pancreatic flow rate, bicarbonate and chloride levels, total protein and enzyme activities were measured. In resting conditions and in response to food, the lipase activity was found to be significantly lower in the group fed with milk replacer, which was poorer in fat. These results indicate an adaptation of the enzyme output to the available quantity of its substrate, similar to that described in the rat. Postprandial differences in the pancreatic flow rate, electrolytes and total protein were found between both groups. Their origin can be attributed to the protein used (soyabean) in the milk substitute. Such soya protein alters the normal clot formation in the abomasum and allows an accelerated abomasal digesta outflow and duodenal pH alkalinisation.

Adaptation, Physiological↗

The role of the bovine growth hormone receptor and prolactin receptor genes in milk, fat and protein production in Finnish Ayrshire dairy cattle.

We herein report new evidence that the QTL effect on chromosome 20 in Finnish Ayrshire can be explained by variation in two distinct genes, growth hormone receptor (GHR) and prolactin receptor (PRLR). In a previous study in Holstein-Friesian dairy cattle an F279Y polymorphism in the transmembrane domain of GHR was found to be associated with an effect on milk yield and composition. The result of our multimarker regression analysis suggests that in Finnish Ayrshire two QTL segregate on the chromosomal region including GHR and PRLR. By sequencing the coding sequences of GHR and PRLR and the sequence of three GHR promoters from the pooled samples of individuals of known QTL genotype, we identified two substitutions that were associated with milk production traits: the previously reported F-to-Y substitution in the transmembrane domain of GHR and an S-to-N substitution in the signal peptide of PRLR. The results provide strong evidence that the effect of PRLR S18N polymorphism is distinct from the GHR F279Y effect. In particular, the GHR F279Y has the highest influence on protein percentage and fat percentage while PRLR S18N markedly influences protein and fat yield. Furthermore, an interaction between the two loci is suggested.

Amino Acid Substitution↗

Subcutaneous abdominal adipocyte size, a predictor of type 2 diabetes, is linked to chromosome 1q21--q23 and is associated with a common polymorphism in LMNA in Pima Indians.

Large subcutaneous abdominal adipocyte size (s.c. abd. AS) is associated with insulin resistance and predicts type 2 diabetes in Pima Indians. Because type 2 diabetes is familial, we aimed to determine whether mean s.c. abd. AS is also familial and if so, to identify chromosomal regions linked to this measure. Body composition (hydrodensitometry) and mean s.c. abd. AS (fat biopsy) were measured in 295 Pima Indians (179 with normal, 80 with impaired, and 36 with diabetic glucose tolerance) representing 164 nuclear families. Mean s.c. abd. AS, adjusted for age, sex, and percentage body fat was a familial trait (heritability h(2) = 0.48, P < 0.0001). A genome-wide autosomal scan revealed suggestive evidence for linkage (LOD 1.73) of adjusted mean s.c. abd. AS to chromosome 1q21--q23, a region containing LMNA, the gene encoding for the nuclear envelope proteins lamin A/C. Rare mutations in LMNA were recently shown to underlie familial partial lipodystrophy (FPLD), a syndrome characterized by regional loss of adipose tissue, insulin resistance, and glucose intolerance. A common (allelic frequency 0.43) single nucleotide polymorphism (silent 1908C --> T substitution) in exon 10 of LMNA (GenBank X03444) was associated with reduced age-, sex- and percentage body fat-adjusted mean s.c. abd. AS [0.80 +/- 0.17 (CC), 0.76 +/- 0.15 (CT), 0.73 +/- 0.16 (TT) microg lipid/cell, P < 0.05 for CC vs TT]. These findings indicate that approximately half of the variance in mean s.c. abd. AS can be attributed to familial factors and that genetic variation in LMNA might not only underlie rare cases of FPLD, but may also contribute to variation in adipocyte size in the general population.

Adipocytes↗

The Val81 missense mutation of the melanocortin 3 receptor gene, but not the 1908c/T nucleotide polymorphism in lamin A/C gene, is associated with hyperleptinemia and hyperinsulinemia in obese Greek caucasians.

Obesity-related phenotypes have been linked to human chromosomes 1q21 and 20q13, regions where the lamin A/C gene (LMNA) and the melanocortin 3 receptor gene (MC3R) map, respectively. Recently, a common single nucleotide polymorphism (SNP) in LMNA (1908C/T) was associated with plasma leptin and obesity indices in aboriginal Canadians, but these associations have not yet been explored in other populations. In contrast, no significant associations of MC3R variants with obesity have been detected, although a significant association with hyperinsulinemia has been reported in Caucasian populations. We investigated the associations between the LMNA 1908C/T variant and the 241G/A variant of the MC3R gene (Val81Ile missense mutation) and body composition, as well as plasma leptin and insulin levels, in two samples of unrelated healthy Greek subjects. A group of 112 young nonobese subjects, and a group of 116 adult women with a body mass index (BMI) ranging from 23.2 to 47.7 kg/m2 were studied cross-sectionally. We found no significant association of the LMNA 1908C/T and a borderline significant association of MC3R 241G/A SNPs with body composition variables, in the entire study sample. However, unlike the LMNA 1908C/T genetic variation, the MC3R 241G/A genetic variation was significantly associated with hyperleptinemia and huperinsulinemia in obese subjects, and there was evidence of interaction between this polymorphism and fat mass or BMI in predicting hyperinsulinemia. Our results suggest that the LMNA 1908C-->T substitution and the Val81Ile mutation of the MC3R gene are unlikely to be major predictors of body composition in Greek Caucasians, but the latter genetic variation may predispose obese subjects to develop insulin and leptin resistance. Future studies are needed to confirm these data and assess whether individuals carrying this mutation are more resistant to weight-reducing and insulin-sensitizing treatments.

Adult↗

Water maze performance is unaffected in artificially reared rats fed diets supplemented with arachidonic acid and docosahexaenoic acid.

Four groups of male Long-Evans rats were reared artificially from postnatal d 5 to 18 by being fed through a gastrostomy tube with rat milk substitutes containing oils providing 10% linoleic acid and 1% alpha-linolenic acid (g/100 g fat); with the use of a 2 x 2 design, they were fed one of two levels of arachidonic acid (AA) and docosahexaenoic acid (DHA) (0.0 and 2.5 g/100 g of fatty acids). A fifth artificially reared group was fed a diet high in saturated fat, and a sixth group was reared by dams fed a standard AIN-93M diet. The pups were weaned onto modified AIN-93G diets, with a fat composition similar to that fed during the artificial rearing period. Behavioral testing was conducted between 6 and 9 wk of age; brain lipid composition was then assessed. Relative to the unsupplemented group (0.0 g/100 g AA and DHA), dietary supplementation resulted in a wide range of AA (84-103%) and particularly DHA (86-119%) levels in forebrain membrane phospholipids. AA supplementation increased AA levels and decreased DHA levels, and DHA supplementation increased DHA levels and decreased AA levels, with the magnitude of these effects dependent on the level of the other fatty acid. DHA levels were very low in the saturated fat group. The groups did not differ on the place or cued version of the Morris water-maze, but on a test of working memory, the saturated fat group was impaired relative to the suckled control group. Further correlational analyses in the artificially reared animals did not support a relationship between the wide range of DHA and AA levels in the forebrain and working-memory performance.

Animals↗

Feeding lactose-intolerant children with a powdered fermented milk.

Fresh yogurt has been proposed as a milk substitute for lactase-deficient patients. We investigated the possibility that a dried, low-fat milk fermented by yogurt microorganisms would be effective. Processing of a fermented milk by spray-drying led to a powder with persistence of lactase activity (11.7 units/g) without storage at 4 degrees C and stable at room temperature (20-23 degrees C). The tolerance and absorption of 10.5 g of lactose in a volume of 150 ml was studied in 25 Gabonese lactase-deficient children aged 5-14 years in the form of a standard humanized milk formula followed 1 week later by the powdered fermented milk formula. Results of the breath hydrogen test showed that in 24 of 25 cases, lactose absorption was normal with a maximal rise of hydrogen over baseline of under 13 ppm after ingestion of the powdered fermented milk. The rise was above 20 ppm in the 25 children with the same load of lactose in the form of the standard formula and one-third had symptoms of lactose intolerance. This powdered fermented milk preparation should be considered as a valid approach in programs of nutritional support targeted to countries with a high prevalence of lactase deficiency.

Adolescent↗

Switch to efavirenz in a protease inhibitor-containing regimen.

PURPOSE: This report evaluated the efficacy and safety of switching from a protease inhibitor (PI)-containing HIV treatment regimen to an efavirenz (EFV)-containing regimen. METHOD: We retrospectively analyzed data from 64 patients, with a plasma viral load (VL) less than 50 copies/mL and CD4+ counts >200 cells/mL at baseline, who had been taking a regimen consisting of a PI and two nucleoside reverse transcriptase inhibitors (NRTIs; d4T/3TC [n = 45]; AZT/3TC [n = 19]) for a median of 27.5 months (range, 6-41 months) and who chose to substitute EFV for the PIs in the regimens. Statistical analyses were performed by Wilcoxon test. Fat atrophy was evaluated by physician's assessment and patients' subjective self-estimation with the criteria of well being and body state. RESULTS: 57 patients completed 36 weeks on the EFV regimen; 4 patients changed therapy but continued EFV, 2 moved to another area, and 1 discontinued EFV. During the first weeks of therapy, 56.3% of patients suffered from moderate nervous system symptoms. The plasma VL of 63 patients remained at <50 copies/mL at final analysis. Compared with time of switching to EFV, analysis at 36 weeks showed no statistically significant change from 626+/-283 to 643+/-296 cells/mL in mean absolute CD4+ cells and a statistically significant increase from 26.8+/-9.6% to 28.0+/-9.1% in relative CD4+ cells. There was a statistically significant reduction in relative CD8+CD38+ from 62.2+/-16.3% at time of switching to EFV to 55.1+/-15.0% at week 36. At baseline, 27 patients suffered from lipodystrophy, including fat atrophy and fat accumulation. After 36 weeks, nine patients showed intensified fat atrophy. In contrast, five patients improved their state concerning fat redistribution and 13 patients showed no alterations. CONCLUSION: The switch to a non-PI-containing regimen with EFV offers a good drug alternative for patients with suppressed viral load, problems of adherence, and/or adverse events due to PIs but not for patients suffering from lipoatrophy caused by nucleoside reverse transcriptase inhibitors. The intention of such a switch aims at the avoidance of fatal mutations in HIV.

ADP-ribosyl Cyclase↗

Changing concepts in lipid nutrition in health and disease.

Fat remains a hot topic because of concerns over associations between consumption of fats and the incidence of some chronic conditions including coronary artery disease, diabetes, cancer and obesity. Dietary fats serve multiple purposes. The effects of dietary fats generally reflect the collective influences of multiple fatty acids in the diet or food. This presentation highlights some recent developments on the role of dietary fats and oils in health and disease. Debate continues over the role of dietary modification in coronary prevention by lipid lowering. The degree to which a recommended diet will result in health benefits for an individual is difficult to predict, because the outcome will depend on the influence of other factors such as a person's genetic constitution, level of physical activity and total diet composition. There can now be little doubt about the importance of genetic factors in the etiology of cardiovascular disease, diabetes, obesity and cancer. The importance of antioxidant status in the prevention of cardiovascular disease as well as many cancers is being increasingly recognised. It is now evident that not all saturated fatty acids are equally cholesterolemic. Recent accounts evaluating palm oil's effects on blood lipids and lipoproteins suggest that diets incorporating palm oil as the major dietary fat do not raise plasma total and LDL cholesterol levels to the extent expected from its fatty acid composition. Palm oil is endowed with a good mixture of natural antioxidants and together with its balanced composition of the different classes of fatty acids, makes it a safe, stable and versatile edible oil with many positive health and nutritional attributes. In recent times, adverse health concerns from the consumption of trans fatty acids arising from hydrogenation of oils and fats have been the subject of much discussion and controversy. Trans fatty acids when compared with cis fatty acids or unhydrogenated fats have been shown to lower serum HDL cholesterol, raise serum LDL cholesterol and when substituted for saturated fatty acids, increase lipoprotein Lp (a) level, an independent risk factor for the development of coronary heart disease. The idea of which foods, nutrients and supplements are "healthy" is often being amended as new scientific data is presented and then simplified for the consumers. What was once perceived as a healthy diet is often no longer considered as such and vice versa. Dietary recommendations have to change with time and the evidence available. Nutritional recommendations should encourage eating a great variety of nutrient sources within our food supply in moderation. Various lifestyle options to improve health should also be promoted.

Disease↗

Interaction of dietary saturated and polyunsaturated triglycerides in regulating the processes that determine plasma low density lipoprotein concentrations in the rat.

These studies were undertaken to determine how polyunsaturated (n-3 and n-6) and saturated triglycerides interact to regulate rates of low density lipoprotein (LDL) production and rates of receptor-dependent and receptor-independent LDL transport. Animals were fed diets containing 20% (by wt) hydrogenated coconut oil or diets in which the coconut oil was progressively removed and replaced with safflower oil or fish oil concentrate. Plasma LDL concentrations fell when either of the polyunsaturated triglycerides was substituted for saturated triglycleride in the diet; however, the reduction in LDL concentrations was greater with fish oil than with safflower oil at all ratios of polyunsaturated to saturated triglyceride that were examined. The lower plasma LDL concentrations when coconut oil was replaced with fish oil could be attributed almost entirely to a much greater increase in hepatic LDL receptor activity when fish oil was used as the substitute than when safflower oil was used as the substitute. To examine the effect of polyunsaturated triglycerides when used to supplement a high saturated fat diet rather than to replace saturated fat in the diet, animals were fed a diet containing 15% coconut oil (by wt) with or without an additional supplement of 5% fish oil or safflower oil. The addition of 15% coconut oil to low fat control diet increased the rate of LDL production causing circulating LDL levels to rise by 40%. The further supplementation of this high saturated fat diet with fish oil concentrate markedly increased hepatic LDL receptor activity causing plasma LDL concentrations to return to control values whereas supplementation with safflower oil had little effect. Thus, at least in the rat, supplementation of a high saturated fat diet with a fish oil concentrate lowers plasma LDL concentrations as effectively as removing the saturated fat from the diet, although in the former case, both the production and the receptor-dependent uptake of LDL are greatly increased.

Animals↗

Milk response to concentrate supplementation of high producing dairy cows grazing at two pasture allowances.

Twenty multiparous Holstein cows (four ruminally cannulated) in five 4 x 4 Latin squares with 21-d periods were used to study the effect of concentrate supplementation when grazed at two pasture allowances. The four dietary treatments resulted from the combination of two pasture allowance targets (low, 25 vs. high, 40 kg of dry matter/cow per day) and two concentrate supplementation levels (zero vs. 1 kg of concentrate/4 kg of milk). Concentrate supplementation decreased pasture dry matter intake 2.0 kg/d at the low pasture allowance (17.5 vs. 15.5 kg/d) and 4.4 kg/d at the high pasture allowance (20.5 vs. 16.1 kg/d). Substitution rate was lower at the low pasture allowance (0.26 kg pasture/kg concentrate) than at the high pasture allowance (0.55 kg of pasture/kg of concentrate). Total dry matter intake of both supplemented treatments averaged 24.4 kg/d. Milk production of both supplemented treatments averaged 29.8 kg/d, but was increased with higher pasture allowance in the unsupplemented treatments (19.1 vs. 22.2 kg/d). Milk response to concentrate supplementation was 1.36 and 0.96 kg of milk/kg of concentrate for the low and high pasture allowances, respectively. Concentrate supplementation reduced milk fat percentage but increased milk protein percentage. Rumen pH and NH3-N concentration were decreased with concentrate supplementation. Substitution rate was likely related to both negative associative effects in the rumen (reductions in rumen pH, rate of pasture digestion, and NDF digestibility) and reductions in grazing time. The latter was more important, quantitatively explaining at least 80% of the reduction in pasture dry matter intake observed.

Animal Feed↗

Chicken and fish diet reduces glomerular hyperfiltration in IDDM patients.

OBJECTIVE: To compare the effect of a normal protein diet (test diet) in which chicken and fish were substituted for red meat with a low-protein diet (LPD) on glomerular filtration rate (GFR) in normoalbuminuric insulin-dependent-diabetes mellitus (IDDM) patients. RESEARCH DESIGN AND METHODS: A crossover randomized clinical trial was performed in 15 normoalbuminuric IDDM patients, 9 normofiltering, and 6 hyperfiltering patients. They followed three diets for a 3-week period each: a usual diet (UD), an LPD (0.5 g.kg-1.day-1 of proteins, 7% calories as protein, 33% as fat, and 60% as carbohydrates), and a normoproteic isocaloric test diet in which white meat (chicken and fish) was substituted for red meat of the UD. At the end of each diet, a clinical evaluation and measurements of GFR (51Cr-ethylenediaminetetraacetate (EDTA) single injection technique), urinary albumin excretion (UAE), and plasma amino acids were performed. Dietary compliance was assessed by a 24-h urinary urea and weekly interviews with the dietitian. RESULTS: In all diabetic patients, GFR after the LPD (114.9 +/- 16.5 ml.min-1 x 1.73 m-2) and after the test diet (122.7 +/- 16.7 ml.min-1 x 1.73 m-2) was significantly lower than after the UD (132.0 +/- 27.7 ml.min-1 x 1.73 m-2) (P = 0.001). Similar results were found in the hyperfiltering group: after UD = 161.1 +/- 15.4 ml.min-1 x 1.73 m-2, after LPD = 129.8 +/- 9.0 ml.min-1 x 1.73 m-2, and after the test diet = 136.5 +/- 3.1 ml.min-1 x 1.73 m-2, (P < 0.001). In the normofiltering group, no significant changes in GFR were observed after the three diets. Metabolic control, nutritional indexes, blood pressure (BP), and UAE did not change after the three diets in all patients. CONCLUSIONS: A normoproteic diet with chicken and fish as the only meat protein source decreases the GFR in the hyperfiltering normoalbuminuric IDDM patients. The GFR reduction after this diet is similar to that observed after an LPD.

Adult↗

Direct repeats bind the EcR/USP receptor and mediate ecdysteroid responses in Drosophila melanogaster.

The steroid hormone 20-hydroxyecdysone plays a key role in the induction and modulation of morphogenetic events throughout Drosophila development. Previous studies have shown that a heterodimeric nuclear receptor composed of the EcR and USP proteins mediates the action of the hormone at the transcriptional through binding to palindromic ecdysteroid mediates the action of the hormone at the transcriptional level through binding to palindromic ecdysteroid response elements (EcREs) such as those present in the promoter of the hsp27 gene or the fat body-specific enhancer of the Fbp1 gene. We show that in addition to palindromic EcREs, the EcR/USP heterodimer can bind in vitro with various affinities to direct repetitions of the motif AGGTCA separated by 1 to 5 nucleotides (DR1 to DR5), which are known to be target sites for vertebrate nuclear receptors. At variance with the receptors, EcR/USP was also found to bind to a DR0 direct repeat with no intervening nucleotide. In cell transformation assays, direct repeats DR0 to DR5 alone can render the minimum viral tk or Drosophila Fbp1 promoter responsive to 20-hydroxyecdysone, as does the palindromic hsp27 EcRE. In a transgenic assay, however, neither the palindromic hsp27 element nor direct repeat DR3 alone can make the Fbp1 minimal promoter responsive to premetamorphic ecdysteroid peaks. In contrast, DR0 and DR3 elements, when substituted for the natural palindromic EcRE in the context of the Fbp1 enhancer, can drive a strong fat body-specific ecdysteroid response in transgenic animals. These results demonstrate that directly repeated EcR/USP binding sites are as effective as palindromic EcREs in vivo. They also provide evidence that additional flanking regulatory sequences are crucially required to potentiate the hormonal response mediated by both types of elements and specify its spatial and temporal pattern.

Animals↗