Marginal maternal Zn intake in rats alters mammary gland Cu transporter levels and milk Cu concentration and affects neonatal Cu metabolism

Marginal zinc intake is common and leaves women particularly vulnerable to Zn deficiency due to increased demand for Zn as a consequence of reproduction. Zn deficiency during pregnancy and lactation has been associated with secondary affects on copper metabolism in the offspring; however, the underlying mechanisms are unknown. The effects of marginal maternal Zn intake on maternal and neonatal Cu metabolism were determined in rats. Plasma, milk and tissue Cu and Zn concentrations and plasma and milk ceruloplasmin (Cp) activity were measured in dams fed a control (CON, 25 mg Zn/kg diet) or a marginal Zn diet (ZD, 10 mg Zn/kg diet) and their suckling pups. There was no effect on maternal tissue Cu or Zn or milk Zn concentration; however, plasma Cp activity was higher in dams fed ZD, suggesting that Cp activity may be a useful marker for identifying marginal Zn status. Rats fed ZD had high mammary gland Ctr1, Atp7A and Atp7B levels, milk Cp activity and Cu concentration. Immunostaining and differential centrifugation indicated that ZD also altered Ctr1 and Atp7A localization in the mammary gland. Pups from dams fed ZD had higher small intestine Cu and lower plasma Cu than CON pups. These results suggest that marginal maternal Zn intake during pregnancy and lactation increase mammary gland Cu transporter levels and alter their localization, resulting in high milk Cu levels, possibly in response to transiently elevated plasma Cu levels. The combination of high milk Cu concentration and immature neonatal Cu transport exposes the suckling neonate to excess Cu; however, whether this occurs in humans is not yet known.     

Effect of zinc on biochemical parameters and changes in related gene expression assessed by cDNA microarrays in pituitary of growing rats

OBJECTIVE: The present study simultaneously investigated the effects of different zinc (Zn) levels on the growth performance and relative biochemical parameters in growing rats and analyzed the molecular mechanism of zinc influencing food intake. METHODS: Three diets with different Zn levels--Zn adequate (ZA; 35.94 mg/kg, control), Zn deficient (ZD; 3.15 mg/kg), and Zn overdose (ZO; 347.50 mg/kg)--were fed to rats for 6 wk. Dietary Zn was supplemented with ZnSO4. The relation between zinc and food intake was studied by pituitary cDNA microarrays. RESULTS: Compared with ZA group, rats fed the ZD diet showed decreases in body weight (P < 0.01), food intake (P < 0.05), tissue zinc concentrations (P < 0.01), and specific activities of alkaline phosphatase (P < 0.01) and copper/Zn superoxide dismutase (P < 0.05), whereas the ZO diet had positive effects on body weight (P < 0.05), zinc concentrations (P < 0.01), and alkaline phosphatase activity (P < 0.05). The villi of the jejunum became shorter (P < 0.01), shriveled, and flattened. This change in morphology decreased absorption surface area, and there was a substantial decrease (P < 0.01) in villi number per unit area in ZD rats. Metallothionein concentration was increased in livers of rats fed ZD (P < 0.01) and ZO (P < 0.05) diets. Moreover, ZD and ZO influenced normal growth and development of organs. The results from pituitary cDNA arrays indicated that different Zn levels affect gene expression of appetite-related peptides, including neuropeptide-Y, melanin-concentrating hormone, ghrelin, calcitonin gene-related product, and serotonin. CONCLUSION: The present results showed that zinc deficiency has a negative effect on the growth performance and biochemical parameters of rats. The ZO diet increased body weight (P < 0.05) but had no effect (P > 0.05) on food intake, copper/Zn superoxide dismutase activity, and intestinal morphology. The ZD diet decreased rat food intake by regulating appetite-related gene expression in the pituitary gland.     

Long-term marginal intakes of zinc and retinol affect retinol homeostasis without compromising circulating levels during lactation in rats.

Marginal zinc or vitamin A intake is more common than previously thought in industrialized and developing countries, with pregnant and lactating women believed to be particularly at risk. However, the lack of sensitive indicators of zinc and vitamin A status precludes accurate assessment of marginal nutriture. Concurrent deficiencies in zinc and vitamin A intake often coexist, and the interaction between zinc deficiency and vitamin A metabolism may confound results from epidemiologic or intervention studies. To investigate effects of a maternal diet chronically restricted in zinc or vitamin A intake on indices of vitamin A metabolism, we fed rats a control diet (C) or a diet marginal in zinc (ZD), marginal in vitamin A (AD), marginal in both (DD) or pair-fed to DD (PF), preconception through lactation. Plasma retinol (ROH) was greater and retinol binding protein (RBP) was lower in rats fed ZD, AD and DD compared with those fed C. Hepatic cellular retinol binding protein (CRBP) expression was greater than controls in rats fed ZD and AD and lower in those fed DD, whereas RBP expression was greater in the DD- and PF-fed groups compared with rats C. Mammary gland CRBP and RBP expression were not affected by the diets. Milk ROH was lower in rats fed AD, and milk RBP was lower in those fed ZD and DD compared with rats fed C. In summary, chronic, marginal intake of zinc or vitamin A resulted in alterations in tissue retinol metabolism and milk retinol levels without decreasing plasma zinc, retinol or ROH:RBP during lactation. These observations are of concern because these parameters, which are commonly used to assess zinc and vitamin A status, may lead to misassessment of marginal zinc or vitamin A nutriture in some human populations.     

Zinc deficiency is associated with increased brain zinc import and LIV-1 expression and decreased ZnT-1 expression in neonatal rats

Zinc (Zn) deficiency has been associated with adverse behavioral outcomes in infants and children. However, Zn deficiency does not affect brain Zn concentration, suggesting that brain Zn homeostasis is tightly regulated. The recent identification of Zn-specific transport proteins allowed us to examine effects of low Zn intake on tissue Zn level, brain Zn uptake, and zinc transporter expression and localization in neonatal rat brain. Female rats were fed diets differing only in Zn content [7, moderately zinc deficient (ZD); 10, marginally zinc deficient (MZD); or 25 mg Zn/kg, control] and pups were killed on postnatal d 11. Plasma and brain Zn concentrations were measured, brain Zn uptake was assessed using (65)Zn, brain metallothionein-I and -III; LIV-1, zinc transporter ZnT-1, and ZnT-3 expression was measured by semiquantitative RT-PCR. LIV-1 localization in the brain was determined by immunohistochemistry; brain and hippocampi LIV-1 and ZnT-1 protein expressions were measured by Western blotting. Plasma Zn concentration was lower in MZD and ZD pups, whereas brain Zn concentration was not affected. Brain Zn uptake was higher in MZD and ZD rats compared with controls. Metallothionein-I and ZnT-1 expressions were lower and LIV-1 expression was higher in the whole brain of MZD and ZD pups. Metallothionein-III and ZnT-3 mRNA expressions were not affected. LIV-1 was localized to the plasma membrane of many brain cell types, including hippocampal pyramidal neurons and the apical membrane of the choroid plexus. Our results indicate that Zn deficiency results in alterations in Zn transporter expression, which facilitates increased brain Zn uptake and results in the conservation of brain Zn during Zn deficiency.     

Zinc transporters in the rat mammary gland respond to marginal zinc and vitamin A intakes during lactation

Marginal intake of zinc and vitamin A is common during lactation and a deficiency of one micronutrient can result in a secondary deficiency of the other. However, the resistance of milk zinc (Zn) concentration to changes in dietary Zn or vitamin A indicates tight regulation of mammary gland Zn transport. Although several mammalian proteins have been identified and implicated in Zn transport, the mechanisms responsible for mammary gland Zn transport and their regulation by dietary Zn and vitamin A are unknown. In this study, we identified mammary gland Zn transporters and determined effects of marginal Zn and vitamin A intakes on their levels. Rats were fed a control [25 mg Zn/kg, 4 retinol equivalents (RE)/g], a low Zn (10 mg Zn/kg), a low vitamin A (0.4 RE/g), or a low Zn (10 mg Zn/kg) and vitamin A (0.4 RE/g) diet throughout lactation. ZnT-1, ZnT-2 and ZnT-4 were identified in the mammary gland and localized to the serosal membrane (ZnT-1) or intracellularly (ZnT-2 and ZnT-4) by immunostaining. Rats fed a low Zn or low vitamin A diet had lower ZnT-1 protein and higher ZnT-4 mRNA expression and protein levels compared with controls. There was a significant interaction between dietary Zn and vitamin A on zinc transporter mRNA expression and protein levels. Although total mammary gland Zn was not affected, mammary gland metallothionein levels were lower in rats fed low Zn and higher in rats fed low vitamin A, suggesting different mechanisms regulating zinc transporter levels. These results indicate that milk Zn level is maintained through coordinated regulation of mammary gland zinc transporters and documents an effect of vitamin A on zinc homeostasis at the molecular level during lactation.     

Marginal maternal zinc deficiency in lactating mice reduces secretory capacity and alters milk composition

Dietary analysis predicts that marginal Zn deficiency is common in women of reproductive age. The lack of reliable biomarkers limits the capacity to assess Zn status and consequently understand effects of maternal Zn deficiency. We determined effects of marginal maternal Zn deficiency on mammary gland function, milk secretion, and milk composition in mice. Mice (n = 12/diet) were fed marginal (ZD; 15 mg Zn/kg diet) or adequate (ZA; 30 mg Zn/kg diet) Zn diets for 30 d prior to conception through mid-lactation. Mice fed the ZD had a higher plasma Zn concentration (~20%; P < 0.05) but lower milk Zn concentration (~15%; P < 0.05) compared with mice fed the ZA. ZnT2 abundance was higher (P < 0.05) in mice fed the ZD compared with mice fed the ZA; no effect on ZnT4 abundance was detected. The Zn concentration of mammary gland mitochondria tended to be ~40% greater in mice fed ZD (P = 0.07); this was associated with apoptosis and lower milk secretion (~80%; P < 0.01). Total milk protein was ~25% higher (P < 0.05), although the abundance of the major milk proteins (caseins and whey acidic protein) was lower (P < 0.05) in mice fed the ZD. Proteomic analysis of milk proteins revealed an increase (P < 0.05) in four proteins in mice fed the ZD. These findings illustrate that marginal maternal Zn deficiency compromises mammary gland function and milk secretion and alters milk composition. This suggests that lactating women who consume inadequate Zn may not produce and/or secrete an adequate amount of high quality milk to provide optimal nutrition to their developing infant.     

Moderate zinc deficiency reduces testicular Zip6 and Zip10 abundance and impairs spermatogenesis in mice

Male infertility accounts for ~40% of cases of failure to conceive. Testes have a strict zinc (Zn) requirement and severe Zn deficiency compromises spermatogenesis, sperm viability, and motility, compromising fertility in men. Despite the high prevalence of marginal Zn deficiency in humans, less emphasis has been placed on understanding the consequences on male reproduction. Swiss Webster mice were used to visualize Zip protein expression during spermatogenesis using immunohistochemistry. Data suggest Zip5 imports Zn into Sertoli cells and spermatocytes, augmented by Zip10 (primary spermatocytes) and Zip8 (secondary spermatocytes). Zip6, 8, and 10 expression was retained in round spermatids, although Zip8 and Zip10 expression disappears during spermatid maturation. Zip1 and Zip6 expression was detected in mature, elongated spermatids. Zip14 was detected in undifferentiated spermatogonia and Leydig cells. Mice fed diets (n = 10/group) reduced in Zn concentration [marginal-Zn diet (MZD), 10 mg Zn/kg; low-Zn diet (ZD), 7 mg Zn/kg] for 30 d had >35% lower liver Zn concentrations than mice fed the control diet (C; 30 mg Zn/kg) (P < 0.05). Plasma Zn and testosterone concentrations and the testes Zn concentration and weight were not significantly lower than in controls. Plasma Zn was greater in the ZD group than in the C and MZD groups. Mice fed ZD had a reduced number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells (~50%; P < 0.05), compromised seminiferous tubule structure, and reduced Zip10 and Zip6 abundance (>50%; P < 0.5) compared with mice fed C. Our data provide compelling evidence that reduced Zn intake may be associated with infertility in men, perhaps independent of decreased levels of circulating Zn or testosterone, which warrants further investigation in human populations.     

Effects of marginal zinc deficiency on subclinical lead toxicity in the rat neonate

Influence of maternal dietary zinc intake on tissue distribution of lead and zinc in neonatal rats administered lead acetate by gavage during lactation was examined. Milk from dams fed a marginally deficient diet (6 micrograms Zn/g diet) contained a lower zinc concentration at the beginning of lactation than did that from control dams (30 micrograms Zn/g diet); no differences were seen by d 11 of lactation. Dams fed the deficient diet had lower plasma zinc values in comparison with pair-fed or ad libitum-fed dams and lower femur zinc concentration in comparison with pair-fed dams. Pups suckling marginally deficient dams had lower concentrations of zinc in plasma, femurs and kidneys although hippocampal and cerebellar zinc were unaltered. Body weights of pups from marginally zinc-deficient dams were lower than those from ad libitum-fed dams, but similar to those from pair-fed dams. Lead ingestion had no effect on body weight. Marginally zinc-deficient pups had greater lead accumulation in blood, femurs, hippocampi and cerebella, but not kidney, than did zinc-adequate pups. Marginal zinc deficiency during lactation increases the body lead burden of suckling rats, an effect not attributable to increased transfer of lead into milk in response to suboptimal maternal zinc status.     

Utilization of zinc from picolinic or citric acid complexes in relation to dietary protein source in rats

Young male Sprague-Dawley rats were divided in 18 groups of eight animals each and were fed ad libitum for 24 d a purified diet with 20% casein, whey protein or serum albumin as protein source. Each diet was supplemented with zinc picolinate, zinc citrate or zinc sulfate to a level of dietary zinc equal to 5 or 10 ppm. The source of zinc had no significant effect on zinc utilization with any of the three dietary proteins or at either dietary zinc concentration. With the 5 ppm Zn diet zinc concentration in the serum, but not weight gain or the zinc concentration in femur, testis or whole body was lower in rats fed the casein diet than in those fed the whey diet. Zinc concentrations in serum, femur, testis and whole body, but not weight gain, were lower in rats fed the casein diet than in those fed the serum albumin diet. With the 10 ppm Zn diet, zinc concentrations in serum, femur and whole body, but not weight gain nor zinc concentration in testis, were lower in rats fed the casein diet than in those fed either of the other diets. These results suggest that the reason for the lower utilization of zinc from cow milk in comparison to human milk may be the higher casein concentration in cow milk.     

Low vitamin a intake affects milk iron level and iron transporters in rat mammary gland and liver

Marginal vitamin A deficiency is common and can result in a secondary iron (Fe) deficiency. A positive correlation between maternal Fe status and milk Fe was observed in lactating women supplemented with both vitamin A and Fe but not with Fe alone, suggesting effects of vitamin A on mammary gland Fe transport. We hypothesized that low vitamin A intake during lactation elicits differential effects on mammary gland and liver Fe transport and storage proteins, thus affecting milk Fe concentration but not maternal Fe status. We fed rats a control (CON, 4 RE/g) or a marginal vitamin A diet (AD, 0.4 RE/g) through midlactation. Effects on plasma, milk, liver and mammary gland Fe and vitamin A concentrations, and divalent metal transporter-1 (DMT1), ferroportin (FPN), ferritin (Ft), and transferrin receptor (TfR) expression were determined. Dams fed AD were not vitamin A or Fe deficient. Milk and liver vitamin A and Fe and mammary gland Fe concentrations were lower in rats fed AD compared with rats fed CON. Liver TfR expression was higher, whereas mammary gland TfR expression was lower in rats fed AD compared with rats fed CON. Liver Ft was unaffected, whereas mammary gland Ft was lower in rats fed AD compared with rats fed CON. Liver and mammary gland DMT1 and FPN protein levels were lower in rats fed AD compared with rats fed CON. Our results indicate that the mammary gland and liver respond differently to marginal vitamin A intake during lactation and that milk Fe is significantly decreased due to effects on mammary gland Fe transporters, putting the nursing offspring at risk for Fe deficiency.     

A high dietary lipid intake during pregnancy and lactation enhances mammary gland lipid uptake and lipoprotein lipase activity in rats.

Rats fed a diet with high fat concentration produce larger amounts of milk with a higher lipid concentration than rats fed a lower fat diet. This investigation was designed to study the relationship between dietary fat intake, mammary gland lipid uptake and lipogenesis in rat dams fed, during pregnancy and lactation, one of two purified diets, with equal energy density, containing 2.5 (LL) or 20 g fat/100 g diet (HL). Milk lipid concentration and fatty acid composition were determined at d 14 of lactation. Mammary gland lipogenesis, lipoprotein lipase (LPL) activity and the uptake of [1-(14)C]triolein by the mammary gland and its transfer to the pups was measured. The intestinal absorption of oral (14)C-lipid, (14)CO(2) production and the amount of (14)C-lipid transferred to the pups (milk clot + pups carcass) were significantly higher in the HL group than in the LL group (P < 0.05). Mammary gland lipogenesis was 75% lower and LPL activity was 30% higher in the HL group (P < 0.05). Medium-chain fatty acids (C6-C14) excretion was 46% lower and that of long-chain fatty acids was 142% (P < 0.001) higher in the HL group than in the LL group. The higher milk lipid excretion in the rats fed a high-fat diet resulted from a larger uptake of dietary lipid by the mammary gland, indicated by a larger transfer of (14)C-lipid to the pups and by a higher LPL activity in the mammary gland.     

锌对热应激大鼠垂体POMC mRNA表达的影响

目的：通过锌对热应激大鼠垂体阿黑皮素原（ＰＯＭＣ）ｍＲＮＡ表达的影响研究，探讨锌对热应激大鼠的保护机理。方法：２０只ＳＤ雄性大鼠随机等分４组，即高锌高温暴露组（Ａ组）、中锌高温暴露组（Ｂ组）、低锌高温暴露组（Ｃ组）和正常锌室温对照组（Ｄ组）。在ＡＩＮ－９３Ｍ饲料配方基础上，以碳酸锌为锌源，配制成高锌、中锌、低锌和正常锌饲料，每公斤饲料锌含量测定值分别为９２．２ｍｇ、４５．６１ｍｇ、２１．７０ｍｇ和４５．６１ｍｇ。４组大鼠在室温下饲以相应饲料１４天后，将Ａ、Ｂ、Ｃ组大鼠置于高温室（Ｔｄｂ４０℃，Ｔｗｂ３０．８℃）中连续暴露３小时。用Ｎｏｒｔｈｅｒｎｂｌｏｔ杂交分析法（探针为地高锌标记的ＰＯＭＣｃＲＮＡ），观察垂体ＰＯＭＣｍＲＮＡ表达水平。结果：（１）高温应激可使大鼠垂体ＰＯＭＣｍＲＮＡ表达水平增高；（２）高锌摄入可使热应激大鼠垂体ＰＯＭ－ＣｍＲＮＡ表达水平升高，而低锌摄入则相反。结论：锌对热应激大鼠垂体ＰＯＭＣ基因有调控作用，作用环节可能在转录水平上     

Marginal zinc deficiency exacerbates experimental colitis induced by dextran sulfate sodium in rats

We investigated the impact of Zn status on the maintenance of mucosal homeostasis. Rats were fed diets containing different amounts of Zn (30, 10, 5, <1 mg Zn/kg diet) for 21 d. Serum Zn concentrations were lower in rats fed marginally Zn-deficient (MZD; 5 mg Zn/kg diet) and severely Zn-deficient (<1 mg/kg) diets but not in those fed the marginally Zn-adequate diet (10 mg/kg) or the Zn-adequate (ZA; 30 mg/kg) group (P < 0.05). However, organ weights, colonic epithelial cell proliferation, and crypt fission did not differ between the MZD and ZA groups. We then evaluated whether MZD modulated dextran sulfate sodium (DSS)-induced colonic inflammation by administering 2% DSS to the MZD and ZA groups for 7 d. Myeloperoxidase activity and TNFα production increased in response to DSS in the MZD group (P < 0.03). Colonic permeability in the 2 groups did not differ after DSS administration. In a culture experiment using isolated mesenteric leukocytes, TNFα production was higher (P < 0.05) and TNF receptor type I (TNFR1) expression was detected in culture medium containing 20 and 30 μmol/L of Zn compared with culture medium lacking Zn supplementation. These results suggest that MZD exacerbated colitis by modulating the immune response through the impairment of TNFα production and TNFR1 expression rather than through the impairment of epithelial barrier function.     

Vitamin A during lactation: relationship of maternal diet to milk vitamin A content and to the vitamin A status of lactating rats and their pups

We have investigated the effects of maternal vitamin A intake during pregnancy and lactation or during lactation alone on the concentration of vitamin A in rat's milk and on vitamin A levels in plasma and liver of dams and their pups. Groups of Sprague-Dawley rats were fed diets having either a high vitamin A content [15 retinol equivalents (R.E.)/g diet] or a low vitamin A content (0.6 R.E./g) for 42 d, including 7-8 d prior to pregnancy, pregnancy, and for 14 d of lactation. The concentration of vitamin A in milk on d 14 of lactation was significantly greater on the high vitamin A diets [114 +/- 16 micrograms/dl (mean +/- SEM; n = 8) versus 52 +/- 7.3 micrograms/dl (n = 11), P less than 0.005]. However, milk vitamin A concentration on d 1 of lactation did not vary with maternal vitamin A intake during pregnancy. In a second study in which supplementation with vitamin A (30 R.E./g diet) was begun on d 1 postpartum, the milk vitamin A content increased progressively with duration of lactation. Maternal plasma vitamin A concentrations did not differ between rats fed the higher or lower vitamin A diets. However, liver vitamin A concentrations both of dams and of their 14-d-old pups were significantly higher when dams were fed the higher vitamin A diets during pregnancy and/or lactation. The results of these studies indicate that the transfer of vitamin A from mother to offspring by milk and the vitamin A status of dams and their suckling neonates is influenced by maternal vitamin A intake during lactation.(ABSTRACT TRUNCATED AT 250 WORDS)     

锌缺乏对孕鼠及其胎鼠体内元素分布的影响

为了解锌缺乏对妊娠大鼠及胎鼠体内元素分布的影响 ,将Wistar妊娠大鼠分为缺锌组、对喂组、补锌组和对照组 ,分别喂饲缺锌 (0 7mg kg)和正常锌 (10 0mg kg)饲料 ,在妊娠第 2 1天时处死孕鼠 ,取其血液、肝、脾、肾、胎盘和胎鼠 ,用原子吸收分光光度法测定锌、铜、铁、锰、钙含量。结果表明 ,缺锌组孕鼠各组织中锌和其他元素含量均显著低于补锌组和对照组 ;而且其血液、肝、脾、肾脏中铜、铁、锰含量显著低于对喂组 ,说明锌和其他元素在肠道吸收和组织分布方面存在协同关系 ,锌缺乏所致的动物摄食量减少不是引起组织中元素含量降低的主要原因。缺锌组胎盘中铁和胎鼠中铁、钙含量则显著高于其他三组 ,反映了锌与铁元素在胎盘可能存在竞争性转运。提示锌缺乏的母体和胎儿各元素在组织中分布不一致。     

Low intensity exercise and varying proportions of dietary glucose and fat modify milk and mammary gland compositions and pup growth.

Exercise during pregnancy or lactation may create a competition for glucose between the exercising muscle and either the developing fetus or the lactating mammary gland. To test these two hypotheses, pregnant rats were randomly assigned to isoenergetic diets with varying levels of glucose (20, 40 or 60% by weight) and fat (30, 22 or 14%, respectively, by weight) and were rested (R) or exercised (E) on a motorized treadmill at 20 m/min, 60 min/d (low intensity), 7 d/wk throughout pregnancy and lactation. Main effects and selected interactions of diet and exercise during pregnancy and diet, exercise and litter size during lactation were tested using 3 x 2 and 3 x 2 x 2 factorial designs, respectively. Neither diet nor exercise affected pregnancy outcomes. In contrast, during lactation, milk and mammary gland compositions and pup growth were altered. Exercise produced higher milk protein concentrations (40% glucose diet) and lower milk lactose concentrations (20% glucose diet). Exercise also lowered mammary gland fat content and produced higher milk fat concentrations. The 60% glucose diet resulted in the highest milk fat concentrations, but pups of dams fed the 40% diet were heavier on lactation d 15 than pups of dams fed the 60% diet. Taken together, these results support the claim of decreased availability of glucose to the mammary gland for lactose synthesis during chronic low intensity exercise. Additionally, the best lactation performance was not supported by a high carbohydrate (60% glucose), lower fat (14%) intake. A more moderate carbohydrate (40% glucose), higher fat (22%) intake promoted greater pup weights at weaning, suggesting an overlooked role for macronutrient composition in optimizing lactation performance.     

Reevaluation of zinc deficiency on concanavalin-A-induced rat spleen lymphocyte proliferation

Zinc concentrations of serum, nonlymphoid and lymphoid tissues, and the responsiveness of concanavalin-A (Con-A)-stimulated spleen lymphocytes (SL) and cervical lymph node cells ( CLNC ) from ad libitum-fed zinc-deficient (ZD), pair-fed (PF) and ad libitum-fed zinc-adequate rats (AL) were determined. In vitro effects of serum from ZD, PF and AL rats on responsiveness of Con-A-stimulated SL and CLNC were determined. Weanling male Long-Evans rats were fed ad libitum zinc-deficient (less than 1.0 microgram Zn/g diet) and zinc-adequate (20 micrograms Zn/g diet) diets for 7-42 days. Effects of undernutrition on test parameters were determined on PF rats, which received a restricted zinc-adequate diet (restricted in amount to that consumed by ZD rats). Growth, food intake and zinc concentrations in serum, liver and pancreas were significantly depressed in ZD and PF rats. Zinc per gram of thymus tissue and per number of SL was elevated in ZD and PF rats. Spleen lymphocytes from ZD and PF rats displayed equivalent to significantly increased levels of proliferation following stimulation with Con-A. [3H]Thymidine incorporation by Con-A-stimulated SL and CLNC from ZD, PF and AL rats was not significantly different when cultured in medium containing serum from ZD, PF and AL rats. The present study shows that zinc deficiency causes major changes in total-body and organ growth but minor changes in zinc content and mitogen-induced proliferation of lymphocytes.     

Influence of reduced food intake on polyunsaturated fatty acid metabolism in zinc-deficient rats

The influence of reduced food intake on metabolism of liver phospholipids (PL) in zinc-deficient (ZD) rats was measured. Wealing male Long-Evans rats were fed ad libitum zinc-deficient (2 micrograms Zn/g diet) and zinc-adequate (20 micrograms Zn/g diet) diets for 21 days. A pair-fed (PF) group was included. ZD and PF rats displayed significantly increased levels of linoleic (18:2 omega 6) and dihomo-gamma-linolenic acid (20:3 omega 6). Both ZD and PF rats displayed increased levels of gamma-linolenic acid (18:3 omega 6), but the increase was significant only in PF rats. ZD and PF rats displayed decreased levels of arachidonic acid (20:4 omega 6), but the decrease was significant only in PF rats. Both ZD and PF rats displayed significantly reduced levels of 22:5 omega 6. Both ZD and PF rats displayed increased products of delta 6 desaturation and decreased products of delta 5 and delta 4 desaturation. Significantly increased products of delta 9 desaturation were noted in both ZD and PF rats. ZD and PF rats displayed significant increases in C20 elongation products. ZD and PF rats displayed significantly decreased levels of omega 6 metabolites but not total omega 6 acids. ZD rats showed significantly increased levels of total omega 3 acids and omega 3 metabolites. ZD and PF rats showed significant increases in omega 9 acids but not significant changes in omega 9 metabolites. This study does not indicate that zinc affects the delta 6 desaturase in the metabolism of essential fatty acids. The aberrations previously attributed to zinc deficiency are probably due to the accompanying decreased food intake.     

Effects of isolated zinc deficiency on the composition of skeletal muscle, liver and bone during growth in rats

We investigated the effects of zinc deficiency on body composition by using intragastric force-feeding to obviate decreased food intake and altered eating patterns. Weanling male Sprague-Dawley rats were fed a purified zinc-deficient diet: the ad libitum-fed control group (AL; eight rats) was given powdered diet and water containing 25 ppm zinc; the zinc-replete group (ZN; nine rats) was force-fed a diet blended with water containing zinc in an amount of equal caloric intake to the AL group and allowed access to water containing zinc. The zinc intake of ZN rats was approximately twice that of AL rats based on water intake. The zinc-deficient group (ZD; 13 rats) was fed similarly to the ZN group except deionized water was used for diet preparation and drinking water. After 8 d, body and muscle weight were lower in the ZD group than in the ZN group. Femur weights were similar in the two groups. Serum, liver and femur zinc concentrations were 85, 22 and 42% lower, respectively, in the ZD group than in the ZN group. Serum glucose, relative liver weight, liver glycogen and liver lipids were higher, but muscle and liver DNA were lower in the ZD group than in control groups.     

Influence of different levels of dietary pyridoxine on milk composition in the rat

The effects of five different levels of dietary pyridoxine on milk composition were studied in the rat. Sprague-Dawley strain rats received diets containing 1.2, 2.4, 4.8, 9.6 or 19.2 mg pyridoxine-HCl/kg diet throughout growth, gestation and lactation. Milk samples obtained on days 10, 11, and 12 of lactation were similar in concentrations of total fat, solids-not-fat, carbohydrate, casein and non-casein protein for rats fed the five levels of pyridoxine. The level of vitamin B-6 in milk was significantly higher for rats fed 9.6 or 19.2 mg pyridoxine.HCl/kg diet compared to values for rats fed the three lower levels of vitamin. A higher level of dietary pyridoxine (9.6 mg/kg diet) was required to increase the levels of the vitamin in mammary gland and milk than was needed for maternal liver (4.8 mg/kg) or muscle tissue (2.4 mg/kg). The findings indicated that as the level of pyridoxine was decreased in the diet from an apparently adequate level, the concentration of the vitamin in milk decreased before that in liver or muscle tissue. This suggested that the concentration of the vitamin in milk was an indicator of marginal deficiency of vitamin B-6.