Content of essential and toxic trace elements in organs of obese Wistar and Zucker leprfa rats receiving quercetin

BackgroundThe levels of a number of essential and toxic trace elements in organs and tissues are affected by the disruptions in body homeostasis caused by obesity. Some of these elements may also be influenced by the consumption of biologically active substances of polyphenolic origin, which possess potent abilities to complex with transition metal ions.AimsThe aim of this study was to determine the content of essential and toxic trace elements in Wistar outbred and hereditary obese Zucker Lepr^fa (Z) rats consuming a standard balanced diet or hypercaloric diet with excess fat and fructose, supplemented with quercetin or not supplemented.Materials and methodsMale Wistar and Z rats were fed a control AIN-93M-based semi-synthetic diet or a high-fat-high-carbohydrate diet (HFCD, with 30% fat by weight and 20% fructose provided in the drinking water). A portion of the animals in each line and diet group was administered quercetin at 50 mg/kg body weight. Essential trace elements were included in the diets as a high-purity salt mixture. After the termination of feeding on day 63, the livers, kidneys, and brains of the rats were excised and the content of 16 elements (Fe, Mg, Cu, Mn, Co, Se, Zn, Cr, Ni, Al, Cd, As, Pb, V, Cs, and Ag) was measured by inductively coupled plasma mass spectrometry (ICP-MS).ResultsIn the livers of the Z rats, the contents of Co, Zn, Mg, Fe, Se, and V were reduced and the content of Cr was increased compared to that of the Wistar rats. Supplementation with quercetin significantly decreased liver Fe, V, and Se content, which was more noticeable in the Wistar rats than in the Z rats. In kidneys of Z rats consuming control diet, the contents of Co, Cu, and Cs were decreased whereas those of Ni, Al, and Se were increased compared with the contents in the Wistar rats. The same trend was observed with HFCD feeding except for Cs content. Quercetin reduced kidney V content in both rat lines fed both diets, whereas it reduced Se and Cs only in the Z rats fed control diet. In the brains of the Z rats, a large increase was observed in some trace elements including Pb, Cd, Al, Cr, Ni, Fe, and V compared with the levels in the Wistar rat brains. Supplementation of the control diet with quercetin decreased Al and Ni in the brains of the Z rats.ConclusionThere were significant differences in the mineral content of organs between the Wistar and Z rats, with different propensities for obesity. Moreover some of these effects had no straightforward association with decreased feed consumption or hepatic fat accumulation. When introduced into the diets, quercetin affected the content of essential and toxic elements, but with ambiguous physiological significance. Thus, indicators of essential and toxic trace elements deserve to be used in the protocols of preclinical as well as clinical trials of biologically active substances and food supplements.     

Accumulation of heavy metals in rainbow trout Salmo gairdneri (Richardson) maintained on a diet containing activated sewage sludge

Rainbow trout were fed for 10 weeks with a nutritionally balanced diet containing 30% by weight of activated sewage sludge. The whole body concentrations of nine heavy metals (Cr, Mn, Fe, Co, Ni, Cu, Zn, Cd, Pb), together with four major cations (Ca, Mg, Na, K) were determined at the beginning and end of the experiment and at three intermediate stages. Fish fed on the diet containing sewage sludge had significantly elevated levels of Cr, Fe, Ni, Pb and reduced levels of Na and K compared with controls, though the values obtained for all groups fell within the range reported for uncontaminated fish. The Ni and Zn showed a marked increase towards the end of the experiment, suggesting that they might have continued to rise after 70 days.     

Oxidative stress in mice

The aim of this study was to analyze the effect of high dietary Fe on liver antioxidant status in mice fed a corn-oil-enriched diet. Male Balb/c mice were fed for 3 wk with a standard diet enriched with 5% by weight of corn oil with adequate Fe (FCO diet) or supplemented with 1% carbonyl Fe (FCOFe diet). The control group was fed a standard diet. The high-Fe diet induced a twofold increase of hepatic Fe level. However, an increase of thymic Fe level has been induced solely by dietary fat. The hepatic copper (Cu) level slightly decreased in the FCO diet. In the spleen, the high-Fe diet-induced increase of Fe level was negatively correlated with the Cu level. The antioxidant status was influenced by both dietary fat and Fe. Mice fed corn-oil-enriched diets had a higher concentration of thiobarbituric acid-reactive substances (TBARS), with a greater increase in the FCOFe diet. Fatty acid analysis showed decreased n−3 and n−6/n−3 ratio, particularly in the FCOFe diet. Hepatic Cu/Zn superoxide dismutase (CuZn-SOD) activity was decreased in FCO diet, and Fe supplementation caused a further decrease in the enzyme activity. These results suggest that feeding with corn oil-enriched diet increases oxidative damage by decreasing antioxidant enzyme defense. The high-Fe diet additionally affects the antioxidant defense system, further increasing the tissue's susceptibility to lipid peroxidation. Additionally, both corn-oil- and Fe-enriched diets have increased the Cu requirement in mice.     

Dietary carotenoid pigment supplementation influences hepatic lipid and mucopolysaccharide levels in rainbow trout (Oncorhynchus mykiss)

We assessed the effects of dietary carotenoid pigment supplementation on liver histochemistry in the rainbow trout. One hundred and eight rainbow trout (mean mass 266 ± 10 g) were assigned to each of three replicate tanks for each of three dietary treatments; astaxanthin, canthaxanthin, or control at a target dietary inclusion of 100 mg/kg, by top-coating a pigment-free commercially extruded basal diet (Trouw Aquaculture, U.K.). Fish were fed for 3 weeks at a ration of 1.2% body mass/day, in a recirculating freshwater system maintained at 16 °C. Frozen liver sections were stained for total lipids, unsaturated lipids, glycogen, mucopolysaccharides, glycogen phosphorylase and aspartate aminotransferase. Relative amounts were measured quantitatively by image analysis. Carotenoid treatment significantly (P < 0.05) altered the total lipid profile and hepatic mucopolysaccharide contents of livers of rainbow trout. Results are discussed in relation to the catabolic potential of the liver in carotenoid pigment metabolism.     

Effects of Added CeCl<Subscript>3</Subscript> on Resistance of Fifth-Instar Larvae of Silkworm to <Emphasis Type="Italic">Bombyx mori</Emphasis> Nucleopolyhedrovirus Infection

The aim of this study was to investigate the influence of mineral sources on broiler breeders and their offsprings. Broiler breeding hens were fed with diets containing either organic or inorganic trace minerals at equal levels, i.e., (1) control group was fed with basal diet supplemented with inorganic trace minerals; (2) OZ group was fed with organic Zn instead of sulfate; and (3) OTM group was fed with organic Cu, Mn, Zn, and Se instead of inorganic sources. Results indicated that OTM supplementation decreased plasma cholesterol and triglyceride and increased yolk triglyceride via increasing high-density lipid protein cholesterol and decreasing low-density lipid protein cholesterol and very low-density lipid protein (VLDL) in plasma. OZ diets decreased plasma cholesterol and triglyceride mainly by reducing VLDL concentration. For control group, increased lipid concentrations resulted in increased lipid peroxidation in serum and malondialdehyde retention in yolk. Zn retention was not affected. Otherwise, OZ diet was observed to decrease Cu in yolk and albumen. While for OTM group, albumen Cu, albumen Se, and hepatic Se of hatched chicks were increased, but yolk Cu was decreased. Moreover, organic mineral supplementations improved broilers’ growth performance. In conclusion, organic mineral supplementation in breeders’ diets protected breeders from lipid peroxidation, increased egg nutrition retention, and benefit for growth of broilers.     

Effects of glutamine on growth performance,nutrient content,fatty acid profile,and blood parameters of rainbow trout (Oncorhynchus mykiss)

In this study, different amounts of glutamine were added to the diet of rainbow trout, and they were then fed for a period of 90 days. The current research investigated the effects of glutamine on various aspects of rainbow trout, including growth performance, condition factor, viscerosomatic index, hepatosomatic index, carcass composition, fatty acid profile, hematological parameters, and biochemical parameters. The study's findings revealed that adding glutamine to the diet of rainbow trout had a beneficial impact on their growth features. The rainbow trout group that was fed a 2% concentration of glutamine experienced the most notable increase in growth rate. A statistically significant difference in growth was observed among all groups (p < 0.05). Adding glutamine to the diet increased the amount of protein and decreased the fat content in the flesh of the fish. Glutamine exerted an influence on the blood and biochemistry parameters of fish, as well as their fatty acid composition. In conclusion, the inclusion of glutamine in the diet of fish could potentially enhance their immune system, improve the quality of their muscles, and enhance their growth performance.     

Effects of dehulling,steam-cooking and microwave-irradiation on digestive value of white lupin (Lupinus albus) seed meal for rainbow trout (Oncorhynchus mykiss) and Atlantic salmon (Salmo salar)

A digestibility trial was conducted to assess the effect of dehulling, steam-cooking and microwave-irradiation on the apparent digestibility of nutrients in white lupin (Lupinus albus) seed meal when fed to rainbow trout (Oncorhynchus mykiss) and Atlantic salmon (Salmo salar). Six ingredients, whole lupin seed meal (LSM), dehulled LSM, dehulled LSM steam-cooked for 15 or 45 min (SC15 and SC45, respectively) and LSM microwave-irradiated at 375 or 750 W (MW375 and MW750, respectively), were evaluated for digestibility of dry matter, crude protein (CP), lipids, nitrogen-free extractives (NFE) and gross energy (GE). The diet-substitution approach was used (70% reference diet + 30% test ingredient). Faeces from each tank were collected using a settlement column. Dehulled LSM showed higher levels of proximate components (except for NFE and crude fibre), GE and phosphorus in comparison to whole LSM. Furthermore, SC15, SC45, MW375 and MW750 showed slight variations of chemical composition in comparison to dehulled LSM. Results from the digestibility trial indicated that dehulled LSM, SC15, SC45 and MW375 are suitable processing methods for the improvement of nutrients’ apparent digestibility coefficient (ADC) in whole LSM. MW750 showed a lower ADC of nutrients (except for CP and lipids for rainbow trout) in comparison with MW350 for rainbow trout and Atlantic salmon, suggesting a heat damage of the ingredient when microwave-irradiation exceeded 350 W.     

Inflammation neither increases hepatic hepcidin nor affects intestinal 59Fe-absorption in two murine models of bowel inflammation,hemizygous TNFΔARE/+ and homozygous IL-10−/− mice

Hepcidin-synthesis was reported to be stimulated by inflammation. In contrast, hepcidin synthesis was inhibited by TNFα and serum hepcidin was low. To elucidate these contradictions, we compare data on hepcidin expression, on iron absorption and homoeostasis and markers of inflammation between two murine models of intestinal inflammation and corresponding wild-types as determined by standard methods.In TNF^ΔARE/+ and IL-10^−/−-mice hepatic hepcidin expression and protein content was significantly lower than in corresponding wild-types. However, ⁵⁹Fe whole-body retention showed no difference between knock-outs and corresponding wild-types 7d after gavage, in neither strain. Compared to wild-types, body weight, hepatic non-haem iron content, hemoglobin and hematocrit were significantly decreased in TNF^ΔARE/+ mice, while erythropoiesis increased. These differences were not seen in IL-10^−/− mice. Duodenal IL-6 and TNFα content increased significantly in TNF^ΔARE/+ mice, while ferritin-H decreased along with hepatic hepcidin expression, ferritin L, and non-haem iron. In IL-10^−/− mice, these changes were less marked or missing for non-haem iron. Duodenal ferritin-L and ferroportin increased significantly, while HFE decreased.Our results corroborate the conflicting combination of low hepcidin with inflammation and without increased intestinal iron absorption. Speculating on underlying mechanism, decreased hepcidin may result from stimulated erythropoiesis. Unaltered intestinal iron-absorption may compromise between the stimulation by increased erythropoiesis and inhibition by local and systemic inflammation. The findings suggest intense interaction between counterproductive mechanisms and ask for further research.     

Effects of excess dietary iron and fat on glucose and lipid metabolism

PurposeDiets rich in fat and energy are associated with metabolic syndrome (MS). Increased body iron stores have been recognized as a feature of MS. High-fat diets (HFs), excess iron loading and MS are closely associated, but the mechanism linking them has not been clearly defined. We investigated the interaction between dietary fat and dietary Fe in the context of glucose and lipid metabolism in the body.MethodsC57BL6/J mice were divided into four groups and fed the modified AIN-93G low-fat diet (LF) and HF with adequate or excess Fe for 7 weeks. The Fe contents were increased by adding carbonyl iron (2% of diet weight) (LF+Fe and HF+Fe).ResultsHigh iron levels increased blood glucose levels but decreased high-density lipoprotein cholesterol levels. The HF group showed increases in plasma levels of glucose and insulin and insulin resistance. HF+Fe mice showed greater changes. Representative indices of iron status, such hepatic and plasma Fe levels, were not altered further by the HF. However, both the HF and excess iron loading changed the hepatic expression of hepcidin and ferroportin. The LF+Fe, HF and HF+Fe groups showed greater hepatic fat accumulation compared with the LF group. These changes were paralleled by alterations in the levels of enzymes related to hepatic gluconeogenesis and lipid synthesis, which could be due to increases in mitochondrial dysfunction and oxidative stress.ConclusionsHigh-fat diets and iron overload are associated with insulin resistance, modified hepatic lipid and iron metabolism and increased mitochondrial dysfunction and oxidative stress.     

Hepcidin regulation of ferroportin 1 expression in the liver and intestine of the rat

Hepcidin has been implicated as the iron stores regulator: a hepatic signaling molecule that regulates intestinal iron absorption by undefined mechanisms. The possibility that hepcidin regulates the expression of ferroportin 1 (FPT1), the basolateral iron transporter, was examined in rats after administration of LPS, an iron chelator, or His-tagged recombinant hepcidin (His-rHepc). In the liver, LPS stimulated a biphasic increase of hepcidin mRNA with peaks of mRNA at 6 and 36 h. Concurrently, hepatic FPT1 mRNA expression decreased to minimal level at 6 h and then increased with a peak at 24-36 h. LPS also induced biphasic changes in intestinal FPT1 mRNA expression, with decreased levels at 6 h and increased expression at 48 h. Whereas the initial decrease of FPT1 coincides with an LPS-induced decrease in serum iron, both intestinal and hepatic FPT1 expression recovered, whereas serum iron concentration continued to decrease for at least 24 h. Dietary iron ingestion increased intestinal ferritin protein production but did not reduce intestinal FPT1 mRNA expression. The iron chelator pyrrolidinedithiocarbamate (PDTC) stimulated hepatic hepcidin without suppressing intestinal FPT1 expression. In PDTC-treated rats, LPS stimulated no additional hepatic hepcidin expression but did increase intestinal FPT1 expression. Administration of HisrHepc induced significant reduction of intestinal FPT1 expression. Taken together, these data suggest that hepcidin mediates LPS-induced downregulation of intestinal FPT1 expression and that the hepcidin signaling pathway involves a PDTC-sensitive step.     

Hepatic glucokinase is induced by dietary carbohydrates in rainbow trout, gilthead seabream, and common carp

Glucokinase (GK) plays a central role in glucose homeostasis in mammals. The absence of an inducible GK has been suggested to explain the poor utilization of dietary carbohydrates in rainbow trout. In this context, we analyzed GK expression in three fish species (rainbow trout, gilthead seabream, and common carp) known to differ in regard to their dietary carbohydrate tolerance. Fish were fed for 10 wk with either a diet containing a high level of digestible starch (>20%) or a diet totally deprived of starch. Our data demonstrate an induction of GK gene expression and GK activity by dietary carbohydrates in all three species. These studies strongly suggest that low dietary carbohydrate utilization in rainbow trout is not due to the absence of inducible hepatic GK as previously suggested. Interestingly, we also observed a significantly lower GK expression in common carp (a glucose-tolerant fish) than in rainbow trout and gilthead seabream, which are generally considered as glucose intolerant. These data suggest that other biochemical mechanisms are implicated in the inability of rainbow trout and gilthead seabream to control blood glucose closely.     

Folic Acid and Protein Content in Maternal Diet and Postnatal High-Fat Feeding Affect the Tissue Levels of Iron, Zinc, and Copper in the Rat

Although maternal, fetal, and placental mechanisms compensate for disturbances in the fetal environment, any nutritional inadequacies present during pregnancy may affect fetal metabolism, and their consequences may appear in later life. The aim of the present study is to investigate the influence of maternal diet during gestation on Fe, Zn, and Cu levels in the livers and kidneys of adult rats. The study was carried out on the offspring (n?=?48) of mothers fed either a protein-balanced or a protein-restricted diet (18% vs. 9% casein) during pregnancy, with or without folic acid supplementation (0.005- vs. 0.002-g folic acid/kg diet). At 10?weeks of age, the offspring of each maternal group were randomly assigned to groups fed either the AIN-93G diet or a high-fat diet for 6?weeks, until the end of the experiment. The levels of Fe, Zn, and Cu in the livers and kidneys were determined by the F-AAS method. It was found that postnatal exposure to the high-fat diet was associated with increased hepatic Fe levels (p?相似文献   

Impact of D181V and A69T on the function of ferroportin as an iron export pump and hepcidin receptor

Mutations in the only known mammalian iron exporter ferroportin cause a rare iron overload disorder termed ferroportin disease. Two distinct clinical phenotypes are caused by different disease mechanisms: mutations in ferroportin either cause loss of iron export function or gain of function due to resistance to hepcidin, the peptide hormone that normally downregulates ferroportin. The aim of the present study was to examine the disease mechanisms of the thus far unclassified A69T and D181V ferroportin mutations. We overexpressed wild-type and mutant ferroportin fused to green fluorescent protein in human embryonic kidney cells and used a ⁵⁹Fe-assay, intracellular ferritin concentrations, confocal microscopy and flow cytometry to study iron export function, subcellular localization and the responsiveness to hepcidin. While the A69T ferroportin mutation seems not to affect the iron export function it causes dose-dependent hepcidin resistance. We further found that D181V mutated ferroportin is iron export defective and hepcidin resistant, similar to the loss of function mutations A77D and C367X. This indicates that intact iron export might be necessary for hepcidin-induced downregulation of ferroportin. This hypothesis was investigated by studying the hepcidin response under modulation of iron availability. Incubation of wild-type ferroportin overexpressing cells with holo-transferrin increases the hepcidin effect whereas chelating extracellular ferrous iron causes hepcidin resistance. In this study we present data that postulates to classify the D181V ferroportin mutation as loss of function and the A69T mutation as dose-dependent hepcidin resistant and outline a possible causal link between iron export function and the hepcidin effect.     

The red alga Porphyra dioica as a fish-feed ingredient for rainbow trout (Oncorhynchus mykiss): effects on growth, feed efficiency, and carcass composition

Porphyra dioica meal was added at levels of 5, 10 and 15% to a diet for rainbow trout formulated to be isonitrogenous and isolipidic. The control diet was a commercial trout diet without seaweed meal. The experimental groups were fed in triplicate for 12.5 weeks, during which fish weight increased on average from 107–261 g. Seaweed meal inclusion did not affect significantly weight gain (WG), specific growth rate (SGR), feed efficiency (FE), protein efficiency ratio (PER) and apparent digestibility coefficient of the dry matter (ADC_dm) for any of the diets. Voluntary feed intake (VFI) increased for all seaweed diets compared to the control diet but not significantly (P?>?0.05). Final weight (FW) was significantly smaller for the 15% P. dioica inclusion and hepatosomatic index (HSI) for the 10% and 15% inclusion. Carcass protein content increased for all three experimental diets, and was significantly higher for the diet with 10% seaweed inclusion. Rainbow trout fed with Porphyra meal presented a dark orange pigmentation of the flesh at the end of the trial, compared to the whitish color from the control fish. These results suggest that P. dioica can effectively be included in diets for rainbow trout up to 10% without significant negative effects on weight gain and growth performance. The pigmentation effect of the fish flesh by adding P. dioica meal to the feed is of a considerable interest to the organic salmon-farming industry.     

Mineral supplementation of white wheat flour is necessary to maintain adequate mineral status and bone characteristics in rats

This experiment was designed to compare the effect of ingestion of a wheat flours on mineral status and bone characteristics in rats. White flour was tested either without further mineral supplementation or with Mg, Fe, Zn and Cu supplementation. The flour diets were compared to a control purified diet. Four groups of 10 male Wistar rats each were fed one of the experimental diets for 6 wk and mineral status and tissue retention as well as bone characteristics were determined. As expected, mineral intake, except for calcium, was significantly lesser in rats fed the white flour diet than in the other groups. The rats fed the white flour diet had the lowest food intake, weight gain, fecal excretion and intestinal fermentation. The most important result was that Mg and Fe status were drastically lower in rats fed the white flour diet than in those fed whole flour or control diets. The status of these both elements were significantly improved by the mineral supplementation of white flour. There were no major significant differences between mineral-supplemented white flour and whole flour groups in mineral status. Furthermore, bone mineral densities (total, metaphyseal and diphyseal) were significantly lower in rats fed white flour diet compared to the other diet groups, while no significant difference was observed between the mineral-supplemented white flour, whole flour or control diet groups. In conclusion, the present work shows clearly the importance of mineral-supplementation of white wheat flour to sustain an adequate intake of minerals. Our results indicate also that the whole wheat flour did not negatively alter mineral bioavailability, in comparison to mineral supplemented white flour. Clinical studies are still needed to confirm these rat results in human.     

Zinc supplementation decreases hepatic copper accumulation in LEC rat

The effect of dietary zinc (Zn) supplementation on copper (Cu)-induced liver damage was investigated in Long-Evans Cinnamon rats (LEC), a model for Wilson's disease (WD). Four-week-old LEC (N=64) and control Long-Evans (LE) (N=32) female rats were divided into two groups; one group was fed with a Zn-supplemented diet (group I) and the other was given a normal rodent diet (group II). LEC rats were killed at 6, 8, 10, 12, 18, and 20 wk of age; the LE control rats were killed at 6, 12, 18, and 20 wk of age. Cu concentration in the liver was reduced in LEC rats fed the Zn-supplemented diet compared with LEC rats on the normal diet between 6 and 18 wk of age. Metallothionein (MT) concentration in the livers of LEC rats in group I increased between 12 and 20 wk of age, whereas hepatic MT concentration in LEC rats from group II decreased after 12 wk. Hepatocyte apoptosis, as determined by TUNEL, was reduced in Zn-supplemented LEC rats at all ages. Cholangiocellular carcinoma was observed only in LEC rats in group II at wk 20. These results suggest that Zn supplementation can reduce hepatic Cu concentration and delay the onset of clinical and pathological changes of Cu toxicity in LEC rats. Although the actual mechanism of protection is unknown, it could be explained by sequestration of dietary Cu by intestinal MT, induced by high dietary Zn content.     

Postprandial regulation of hepatic microRNAs predicted to target the insulin pathway in rainbow trout

Rainbow trout are carnivorous fish and poor metabolizers of carbohydrates, which established this species as a model organism to study the comparative physiology of insulin. Following the recent characterisation of key roles of several miRNAs in the insulin action on hepatic intermediary metabolism in mammalian models, we investigated the hypothesis that hepatic miRNA expression is postprandially regulated in the rainbow trout and temporally coordinated in the context of insulin-mediated regulation of metabolic gene expression in the liver. To address this hypothesis, we used a time-course experiment in which rainbow trout were fed a commercial diet after short-term fasting. We investigated hepatic miRNA expression, activation of the insulin pathway, and insulin regulated metabolic target genes at several time points. Several miRNAs which negatively regulate hepatic insulin signaling in mammalian model organisms were transiently increased 4 h after the meal, consistent with a potential role in acute postprandial negative feed-back regulation of the insulin pathway and attenuation of gluconeogenic gene expression. We equally observed a transient increase in omy- miRNA-33 and omy-miRNA-122b 4 h after feeding, whose homologues have potent lipogenic roles in the liver of mammalian model systems. A concurrent increase in the activity of the hepatic insulin signaling pathway and the expression of lipogenic genes (srebp1c, fas, acly) was equally observed, while lipolytic gene expression (cpt1a and cpt1b) decreased significantly 4 h after the meal. This suggests lipogenic roles of omy-miRNA-33 and omy-miRNA-122b may be conserved between rainbow trout and mammals and that these miRNAs may furthermore contribute to acute postprandial regulation of de novo hepatic lipid synthesis in rainbow trout. These findings provide a framework for future research of miRNA regulation of hepatic metabolism in trout and will help to further elucidate the metabolic phenotype of rainbow trout.