Concurrent nematode infection and pregnancy induce physiological responses that impair linear growth in the murine foetus.

This study examined concurrent stresses of nematode infection and pregnancy using pregnant and non-pregnant CD1 mice infected 3 times with 0, 50 or 100 Heligmosomoides bakeri larvae. Physiological, energetic, immunological and skeletal responses were measured in maternal and foetal compartments. Resting metabolic rate (RMR) was elevated by pregnancy, but not by the trickle infection. Energy demands during pregnancy were met through increased food intake and fat utilization whereas mice lowered their body temperature during infection. Both infection and pregnancy increased visceral organ mass and both altered regional bone area and mineralization. During pregnancy, lumbar mineralization was lower but femur area and mineralization were higher. On the other hand, infection lowered maternal femur bone area and this was associated with higher IFN-gamma in maternal serum of heavily infected pregnant mice. Infection also reduced foetal crown-rump length which was associated with higher amniotic fluid IL-1 beta.

Teaching subjects with type 2 diabetes how to incorporate sugar choices into their daily meal plan promotes dietary compliance and does not deteriorate metabolic profile.

OBJECTIVE: To determine whether teaching free-living subjects with type 2 diabetes how to incorporate added sugars or sweets into their daily meal plan results in a greater consumption of calories (fat or sugar) and deteriorates their glycemic or lipid profiles but improves their perceived quality of life. RESEARCH DESIGN AND METHODS: In an 8-month randomized controlled trial, 48 free-living subjects with type 2 diabetes were taught either a conventional (C) meal plan (no concentrated sweets) or one permitting as much as 10% of total energy as added sugars or sweets (S). Mean individual nutrient intake was determined using the average of six 24-h telephone recalls per 4 months. Metabolic control and quality of life were evaluated every 2 months. Quality of life was assessed using the Medical Outcome Survey and the Diabetes Quality of Life questionnaire. RESULTS: The S group did not consume more calories (fat or sugar) and in fact ate significantly less carbohydrate (-15 vs. 10 g) and less starch (-7 vs. 8 g) and had a tendency to eat fewer calories (-77 vs. 81 kcal) than the C group. Weight remained stable, and there was no evidence that consuming more sugar worsened metabolic profile or improved their perceived quality of life. CONCLUSIONS: Giving individuals with type 2 diabetes the freedom to include sugar in their daily meal plan had no negative impact on dietary habits or metabolic control. Health professionals can be reassured and encouraged to teach the new "sugar guidelines," because doing so may result in a more conscientious carbohydrate consumption.

Increased fat intake during lactation modifies hypothalamic-pituitary-adrenal responsiveness in developing rat pups: a possible role for leptin.

High fat feeding reportedly enhances hypothalamus-pituitary-adrenal (HPA) responses to stress in adult rats. The present study tested whether elevated fat intake during suckling could have short and/or long lasting consequences on HPA regulation in the offspring. Mothers were fed either a control (C; 5% fat) or high fat (HF; 20% fat) diet during the last week of gestation and throughout lactation. After weaning (day 21), pups from C and HF mothers were fed a chow diet. Offspring from both C- and HF-fed mothers were tested for ACTH and corticosterone responses to stress on postnatal days 10 and 35. We found that HF feeding produced higher lipid levels in the milk of HF compared with C lactating rat dams and that offspring of these mothers had significantly increased retroperitoneal fat pad weight and relative adipose mass on day 21 as well as elevated plasma leptin levels on days 10 and 21 of age. After weaning, pups from the HF mothers had lower plasma leptin levels than those from C mothers. Maternal dietary fat affected HPA responsiveness in the offspring in an age-related manner. Neonatal pups (day 10) from the HF mothers exhibited a reduction in the ACTH and corticosterone responses to ether stress. However, in 35-day-old offspring from HF-fed dams, stress-induced ACTH secretion was increased compared with that in pups from the C-fed mothers. These results demonstrate that maternal diet and increased fat intake through the milk are important regulators of HPA responsiveness in neonates and prepubertal rats. During neonatal life, the blunted stress responsiveness seen with elevated fat intake and the resulting high leptin levels might protect the pups from excessive HPA activation. After removal of the maternal dietary influence and reduced leptin levels, enhanced ACTH stress responses are observed as in adult rats fed a HF diet. Because of the inverse relationship between plasma levels of leptin and HPA responses in pups, the possibility exists that the effects of the HF diet on stress responsiveness are mediated by changes in leptin exposure during development.

Predictors of infant birth weight in gestational diabetes.

The objectives were to characterize and determine the predictors of birth weight among women with gestational diabetes mellitus (GDM), and to establish whether these predictors vary by prepregnancy body mass index (BMI). A cohort of 353 women with GDM was examined by using data from clinic charts and the McGill Obstetrical and Neonatal Database. Dietary treatment decreased the rate of weight gain (from 0.35 to 0.16 kg/wk, P < 0.0001) and fasting serum glucose (from 4.8 to 4.2 mmol/L, P < 0.001). Positive predictors of infant birth weight among the underweight and normal-weight women (BMI < or = 26) included prepregnancy BMI, height, parity, prediagnostic rate of weight gain, postprandial serum glucose, and gestational duration. Among the overweight and obese women (BMI > 26) the only variables that predicted increased birth weight were prediagnostic rate of weight gain, and fasting or postprandial serum glucose. Hence, prepregnancy body mass index exerts a strong effect on predictors of infant birth weight in GDM, indicating the need to consider prepregnancy weight in the treatment approach.

Food diversity versus breastfeeding choice in determining anthropometric status in rural Kenyan toddlers.

BACKGROUND: Prolonged breastfeeding in developing countries is routinely recommended as a valuable and cost-effective public health measure to promote early childhood growth. However, the effects of breastfeeding beyond 12 months are unclear, with some studies showing positive, and some showing negative effects. The role of complementary foods for children 1-3 years has been less studied. METHODS: We examined feeding behaviour and illness data in relation to anthropometric status among 154 rural western Kenyan children, aged 12-36 months. RESULTS: There was little difference in anthropometric status between partially breastfed and fully weaned children. Rather, dietary diversity (number of different foods consumed) was strongly and consistently related to anthropometric status in this age group. In addition, early complementation with starchy gruels was associated with stunting. CONCLUSIONS: Public health efforts which focus only on prolonged breastfeeding (>12 months) in developing countries will not ensure adequate early childhood growth. Important complementary feeding recommendations that promote diet diversity, through the inclusion of a variety of foods in the diets of children in the 1-3 year age group, are needed.

PIP: The effects of breast feeding and complementary foods beyond 12 months of age on child growth were investigated in a survey of 154 children 12-36 months of age from rural western Kenya. The children were identified through a door-to-door survey conducted in six villages in Kenya's Busia district in 1988. Three nonconsecutive 24-hour dietary recall interviews were conducted and anthropometric measurements were performed. At the time of the study, 98 children (64%) were fully weaned and 56 (36%) were receiving breast milk in addition to foods from the family's regular diet. Termination of breast feeding generally occurred at 12-17 months of age. Exclusive breast feeding was rarely practiced beyond 3 months of age. Porridge was introduced to 23% of children in the first month of life and 86% were receiving gruel by 4 months of age. Fruit was introduced between 3 and 6 months. 59% of partially breast-fed and 74% of weaned children were consuming leafy green vegetables at the time of the survey. Dietary diversity was consistently, positively associated with nutritional status as well as each of the five anthropometric measures. Introduction of starchy gruels before 6 months of age was associated with stunting. Fully weaned children with low dietary diversity had the lowest height-for-age scores. Interactions between dietary diversity level and feeding group were not significant for any nutrient. These findings indicate a need for greater emphasis in nutrition education programs on increasing dietary diversity among weaning-aged children.

Diet and waist-to-hip ratio: important predictors of lipoprotein levels in sedentary and active young men with no evidence of cardiovascular disease.

OBJECTIVE: Healthy, young men were studied to determine the relationship of energy and nutrient intake and physical activity to concentrations of plasma lipoprotein and cholesteryl ester transfer protein. DESIGN: A cross-sectional study compared active and sedentary male subjects (17 to 35 years old) with no personal or family history of coronary heart disease. Participants kept 20-day food and activity journals. Individual intakes of energy, protein, carbohydrate, fat, saturated fat, monounsaturated fatty acids, polyunsaturated fatty acids, dietary fiber, and alcohol were evaluated. Measurements of blood lipids (total cholesterol and triglycerides, high- and low-density lipoprotein cholesterol); apolipoproteins; cholesteryl ester transfer protein; anthropometric variables (body mass index, waist-to-hip ratio, percentage of body fat); and aerobic capacity were taken during fall and spring data collection periods. SUBJECT SELECTION: Subjects were selected on the basis of normal blood lipid levels, absence of underlying disease, and willingness to comply with their current level of physical activity for the duration of the study. Minimal sample size for statistical power was 12 men per group: 12 of 15 subjects who exercised and 13 of 15 subjects who were sedentary completed all phases of the study. STATISTICAL ANALYSES: Statistical analyses consisted of 2-way analysis of variance (activity level and season). Pearson product moment correlations and multiple regression analyses were conducted to assess whether energy and nutrient intakes, physical activity status, and/or anthropometric variables predicted plasma concentrations of lipids and apolipoproteins. RESULTS: Lower waist-to-hip ratio, and not specifically activity level, was associated with higher levels of high-density lipoprotein cholesterol (HDL-C) and lower levels of low-density lipoprotein cholesterol (LDL-C). Dietary intake of saturated and monounsaturated fats and alcohol predicted changes in some apolipoprotein and lipoprotein levels. APPLICATIONS: Use of waist-to-hip ratio in the primary prevention of coronary heart disease is a simple and cost-effective measure to predict development of abnormal lipoprotein profiles in young men. Specific dietary recommendations include adoption of a heart-healthy diet with emphasis on monounsaturated fatty acids (10% to 12% of energy or one third of total fat intake) and the suggestion that small amounts of alcohol (< 3 drinks per week) may, indeed, be beneficial. Because alcohol and waist-to-hip ratio were both important predictors of LDL-C level, even in active young men, the consumption of low levels of alcohol may be beneficial only if waist-to-hip ratio is maintained within the healthful range by achieving an appropriate balance of physical activity and macronutrient intake.

Vitamin E inhibits fish oil-induced hyperlipidemia and tissue lipid peroxidation in hamsters.

Previous research has linked hyperlipidemia with increased serum concentrations of lipid peroxidation products; however, a specific association between diet-induced oxidative stress and hyperlipidemia has not been studied. In the present study, the relationship between tissue lipid peroxidation and hyperlipidemia induced by ingestion of fish oil was examined. In Experiment 1, male Golden Syrian hamsters were fed semipurified diets composed of 1.6 wt% safflower oil plus 15.0 wt% of either butterfat (BF), safflower oil (SAFF), or high-cholesterol menhaden oil [MHO(H-CHOL)] semipurified diets for 27 d. The cholesterol contents of the diets were adjusted to 0.088%. The MHO(H-CHOL)-fed hamsters exhibited higher serum concentrations of total cholesterol, triglycerides, apolipoprotein B, and lipid peroxides when compared to the BF and SAFF diet groups. In a further study (Experiment 2), hamsters were fed for 27 d three dietary treatments: (i) MHO(H-CHOL) with no vitamin E content; (ii) a low-cholesterol menhaden oil containing high concentrations of vitamin E (2.5 mg tocopherol/g oil or dietary concentrations of 375 mg/kg) [MHO(L-CHOL) + E]; and (iii) the MHO(L-CHOL + E) with added cholesterol (595 mg/kg) [MHO(L-CHOL) + CHOL + E] to match the cholesterol content of the MHO(H-CHOL). The MHO(L-CHOL) + E and MHO(L-CHOL) + CHOL + E diet groups showed lower concentrations of serum cholesterol, triglycerides, and hepatic lipid peroxides than the MHO(H-CHOL)-treated group. Moreover, in contrast to the hypercholesterolemia caused by the MHO(H-CHOL) feeding, the MHO(L-CHOL)+ E and MHO(L-CHOL) + CHOL + E diets did not show a serum cholesterol-elevating action. This study supports the hypothesis that oxidative stress in the Syrian hamster could play a causal role in dietary-induced hyperlipidemia which can be inhibited by high vitamin E intake.

Diet texture modifies outcome of a primary infection with Heligmosomoides polygyrus (nematoda) in mice.

To determine if dietary texture altered the establishment, survival and reproduction of Heligmosomoides polygyrus during a primary infection, commercial mouse chow (Purina Chow) was fed in either pelleted or powdered form to 2 groups of infected BALB/c mice, and a semipurified, biotin-fortified, egg-white-based diet was provided in powdered form to a third group of mice. Diet texture (powdered vs. pelleted) modified parasite establishment, as evidenced by higher worm recovery 6 days postinfection (PI) in both groups of mice fed powdered diets compared with the group fed the pelleted diet, but diet texture had no detectable effect on net or per capita egg production or on day 30 worm survival. However, almost twice as many worms were recovered from mice fed the semipurified, powdered diet than those fed either textural formulation of the commercial mouse chow on day 30 PI, indicating that a dietary component in the semipurified diet, such as the single fiber source cellulose, facilitated parasite survival, or that other ingredients in the commercial mouse chow, perhaps the more complex fiber components, reduced worm survival, or both. We conclude that dietary texture influences parasite establishment and that specific fibers that change texture can individually and independently modify H. polygyrus survival.

Tissue mineral distributions are differentially modified by dietary protein deficiency and a murine nematode infection.

This study was designed to investigate whether mineral concentrations in the spleen, serum, and liver were modified by challenge infection with a gastrointestinal nematode, by infection dose, or by protein deficiency despite adequate dietary intakes of minerals. BALB/c mice fed protein-sufficient (PS, 24%) or protein-deficient (PD, 3%) diets were infected with 100 L3 of Heligmosomoides bakeri, drug-treated, and then re-infected with either 0, 100, or 200 L3. Protein deficiency and infection, but not dose, independently modified tissue mineral distributions. H. bakeri infection lowered serum iron concentrations in both diet groups. Despite this, PD mice had elevated iron and calcium concentrations and Ca/Zn ratio in the spleen as well as Fe/Zn ratio in liver, but they had reduced calcium, zinc, copper, and sulfur concentrations, and Cu/Zn ratio in the liver. Infection reduced calcium and iron concentrations and the Ca/Zn ratio in the spleen. We suggest that tissue mineral distribution is a consequence of Th2 immune and inflammatory responses induced by infection in PS mice and the switch to predominant Th1 inflammation in PD, nematode-infected mice.

Mechanisms underlying reduced expulsion of a murine nematode infection during protein deficiency.

Balb/c mice infected with the gastrointestinal nematode Heligmosomoides bakeri were fed protein sufficient (PS, 24%) or deficient (PD, 3%) diets to investigate whether diet, infection or dose of larval challenge (0, 100 or 200 larvae) influenced gut pathophysiology and inflammation. Among the PS mice, worms were more posteriorad in the intestine of mice infected with 200 compared with 100 larvae, suggesting active expulsion in the more heavily infected mice. This was consistent with the positive correlation between worm numbers and fluid leakage in PS mice; similar patterns were not detected in the PD mice. Infection also induced villus atrophy, which was more pronounced in PS than in PD mice. Our cytokine screening array indicated that infection in PD mice elevated a wide range of pro-inflammatory cytokines and chemokines. Whereas serum leptin concentrations were higher in PD mice, monocyte chemotactic protein-5 (MCP-5) in serum increased with increasing larval dose and concentrations were lower in PD than PS mice. We suggest that elevated MCP-5 together with villus atrophy may contribute to the apparent dose-dependent expulsion of H. bakeri from PS mice but that delayed expulsion in PD mice appeared related to a predominant Th1 cytokine profile that may be driven by leptin.

Re-feeding rapidly restores protection against Heligmosomoides bakeri (Nematoda) in protein-deficient mice.

This study determined whether the timing of re-feeding of protein-deficient mice restored functional protection against the gastrointestinal nematode, Heligmosomoides bakeri. Balb/c mice were fed a 3% protein-deficient (PD) diet and then transferred to 24% protein-sufficient (PS) diet either on the day of primary infection, 10 days after the primary infection, on the day of challenge infection, or 7 days after the challenge infection. Control mice were fed either the PD or PS diet. Onset of challenge, but not primary, infection caused short-term body weight loss, anorexia and reduced feed efficiency. Weight gain was delayed in mice when re-feeding commenced on the day of challenge infection; alkaline phosphatase (ALP) was also elevated in these mice on day 28 post-challenge. In contrast, other re-feeding groups attained similar body weights to PS mice within 4 days and had similar ALP at day 28. Serum leptin was higher in PD than PS mice and positively associated with food intake. As expected, worm survival was prolonged in mice fed the PD diet. However, egg production and worm burdens were similar in all re-feeding groups to the PS mice, indicating that protein re-feeding during either the primary or challenge infection rapidly restored normal parasite clearance.

Oral polyamine administration modifies the ontogeny of hexose transporter gene expression in the postnatal rat intestine.

Gastrointestinal mucosal polyamines influence enterocyte proliferation and differentiation during small intestinal maturation in the rat. Studies in postnatal rats have shown that ornithine decarboxylase (ODC) protein and mRNA peak before the maximal expression of brush-border membrane (BBM) sucrase-isomaltase (SI) and the sugar transporters sodium-dependent glucose transporter 1 (SGLT1) and glucose transporter 2 (GLUT2). This study was undertaken to test the hypothesis that the oral administration of spermidine in postnatal rats upregulates the expression of ODC, thereby enhancing the expression of SI and SGLT1 in the brush-border membrane as well as basolateral membrane-facilitative GLUT2 and Na(+)-K(+)-ATPase. Northern and Western blot analyses were performed with antibodies and cDNA probes specific for SI, SGLT1, GLUT2, alpha(1)- and beta(1)-subunits of Na(+)-K(+)-ATPase, and ODC. Postnatal rats fed 6 mumol spermidine daily for 3 days from days 7 to 9 were killed either on postnatal day 10 (Sp10) or day 13 following a 3-day washout period (Sp13). Sp10 rats showed a precocious increase in the abundance of mRNAs for SI, SGLT1, and GLUT2 and Na(+)-K(+)-ATPase activity and alpha(1)- and beta(1)-isoform gene expression compared with controls. ODC activity and protein and mRNA abundance were also increased in Sp10 animals. The increased expression of these genes was not sustained in Sp13 rats, suggesting that these effects were transient. Thus, 3 days of oral polyamine administration induces the precocious maturation of glucose transporters in the postnatal rat small intestine, which may be mediated by alterations in ODC expression.

Evidence for a critical period during late gestation when maternal dietary carbohydrate is essential for survival of newborn rats.

Two experiments were designed to test the hypotheses that 1) maternal dietary carbohydrate is required on d 20-21 of gestation (gd 20-21), when fetal liver glycogen is accumulating, to ensure the postnatal survival of the newborn rat pup and that 2) the lack of maternal dietary carbohydrate during this critical 2-d period will cause high neonatal mortality. Pregnant dams were fed one of two lipid-based, carbohydrate-restricted experimental diets. In experiment 1, the primary energy source was soybean oil; the diets contained no added glucose but contained 4% glucose-equivalents as lipid-glycerol. In experiment 2, the major lipid component was food-grade oleic acid; this diet was supplemented with 4% glucose. A crossover design was used. For gd 0-19, dams were fed either the high carbohydrate diet (62% glucose) or one of the carbohydrate-restricted diets (4% glucose or 4% lipid-glycerol); beginning on gd 19 and through neonatal d 7 (nd 7), the opposite diet was fed. For controls in each experiment, a high carbohydrate diet (62% glucose) and the respective carbohydrate-restricted diets were fed throughout pregnancy. The results showed that restriction to 4% glucose equivalents beginning on gd 20 resulted in high first-day neonatal mortality that was comparable in magnitude to nd-1 mortality rates in dams fed the carbohydrate-restricted diets throughout pregnancy. Repletion with the high carbohydrate, control diet after gd 19 significantly reduced mortality. These experiments demonstrate that maternal dietary carbohydrate beginning in late gestation is essential for the postnatal survival of rat pups.

Comparison of effects of dietary glucose versus fructose during pregnancy on fetal growth and development in rats.

Dietary carbohydrate during pregnancy is essential. Whether this requirement is specific to glucose was investigated. We examined whether fructose at low, intermediate and high levels can substitute for an isoenergetic amount of glucose by feeding graded levels of both carbohydrates (0, 4, 12, 60%) in a triglyceride-based diet throughout pregnancy. It was concluded that the carbohydrate requirement for the rat during pregnancy is not specific to glucose and that the level, not the type, of carbohydrate was critical (experiment 1). A second aspect of the study (experiment 2) was the comparison of isoenergetic, low carbohydrate diets containing different sources of 4% glucose equivalents: glucose, fructose or lipid-glycerol. Fructose and lipid-glycerol were not equivalent substitutes for glucose in the pregnant rat dam at these very low intakes.

Amniotic fluid composition responds to changes in maternal dietary carbohydrate and is related to metabolic status in term fetal rats.

The objective of this study was twofold: 1) to determine whether amniotic fluid composition responded to differences in the level or source (glucose vs. fructose) of maternal dietary carbohydrate, and 2) to establish whether any dietary-induced changes in amniotic fluid composition correlated with maternal or fetal metabolic status at term. Pregnant rat dams were fed graded levels (0, 4, 12 and 60%) of glucose or fructose in a triglyceride-based diet (Experiment 1) or isoenergetic low carbohydrate diets having 4% glucose equivalents as glucose, fructose, or lipid-glycerol (Experiment 2) throughout pregnancy. Amniotic fluid and maternal and fetal samples were collected at term (d21). Results demonstrated a significant increase in amniotic fluid glucose and a significant decrease in amniotic fluid uric acid as the level of carbohydrate increased in the maternal diet. Pearson correlation coefficients showed amniotic fluid glucose to be positively associated with maternal and fetal liver glycogen and fetal weight; amniotic fluid uric acid and urea nitrogen were negatively correlated with these same measures. Regression analysis indicated that amniotic fluid glucose was predictive of fetal body weight and fetal liver glycogen at term. The findings show that amniotic fluid can be modified by maternal diet and suggest that composition of amniotic fluid might be used as an accessible nutritional indicator of carbohydrate status in the developing fetus.

Effect of low carbohydrate diets during pregnancy on parturition and postnatal survival of the newborn rat pup.

To test the hypothesis that maternal dietary carbohydrate is essential for the postnatal survival of the newborn rat pup, two experiments were designed. Pregnant dams were fed one of two basal carbohydrate-free diets. In experiment 1, the primary energy source was edible oleic acid; in experiment 2, it was soybean oil. Supplemental glucose was substituted for lipid. In experiment 1, pregnant dams were fed 4% dietary glucose for d 0-8 to allow successful implantation, as shown previously. Beginning on d 9 the dams were fed 0, 2, 4, 8, 12 or 62% glucose. Control dams (62% glucose) normally delivered pups weighing 5.6 g on d 21. Dams fed zero glucose delivered pups, weighing 3.1 g, 2 d late. The survivability of the litters increased with maternal dietary carbohydrate. All pups from dams fed 0-4% glucose died within 48 h. Pup survival to d 7 was 10% at 8% glucose, 23% at 12% glucose and 82% at 62% glucose. In experiment 2 soybean oil-based diets (basal supplied ca. 4% glycerol) with 0, 4, 12 and 62% glucose were fed from d 0. At zero glucose, fewer dams delivered late and birth weights were greater than in experiment 1. However, all pups born to zero-glucose dams died by d 4. Pup survival to d 7 was 48% at 4% glucose and 84% at 12% glucose. The data demonstrate that maternal dietary carbohydrate is required for fetal growth, normal parturition and postnatal survival of rat pups. The results indicate that late gestation, parturition and the neonatal period may be especially vulnerable to maternal carbohydrate deprivation.

Gastrointestinal nematodes, nutrition and immunity: breaking the negative spiral.

Nutritionists have long understood that intestinal nematode parasites have deleterious effects on host nutritional status, but only recently has the importance of malnutrition as a predisposing factor to intestinal nematodes been recognized. Here we review experimental and field studies on the effects of protein, energy, zinc, vitamin A, and iron deficiencies on gastrointestinal (GI) nematodes of humans, livestock, and laboratory rodents, and draw certain conclusions about the state of our current understanding. In general, malnutrition promotes the establishment, survival, and fecundity of these parasites, but the magnitude of the effect depends on factors such as host species, parasite species, particular infection protocol used, magnitude of the infection, severity of the nutritional deficiency, and presence of single or multiple infections and single or multiple nutritional deficiencies. We highlight the Th2 arm of the immune system as a component of primary importance in the association between malnutrition and GI nematode infections. We summarize what is known about underlying mechanisms that may account for the observed patterns. Finally, we suggest future research directions.

Maternal dietary glucose modifies phosphoenolpyruvate carboxykinase (PEPCK) gene expression in the kidney of newborn rats.

The consequence of low maternal dietary glucose on perinatal phosphoenolpyruvate carboxykinase (PEPCK EC 4.1.32) gene expression was investigated. Pregnant rats were fed isoenergetic diets containing graded levels of glucose (0, 12, 24, and 60%) from gestation day 2 to lactation day 15. The postnatal developmental profile of PEPCK mRNA in the neonatal kidney was analysed by Northern blot and presented as PEPCK/GAPDH mRNA ratios. In comparison with the 24 and 60% dietary groups, maternal dietary glucose restriction (0 or 12%) during pregnancy resulted in a significant delay in postnatal renal PEPCK gene expression. In these glucose restricted pups, renal PEPCK mRNA was barely detected at birth and was fully visualized only at 4-6 hr; it peaked 24 hr after birth, which was 12 hr later than pups born to dams fed 24 or 60% glucose diets. These results demonstrate for the first time that maternal dietary glucose can modify postnatal renal PEPCK gene expression during perinatal development when glucose homeostasis via gluconeogenesis is critical for neonatal survival.

Glucose-restricted diets alter milk composition and mammary gland development in lactating rat dams.

To examine the effects of chronic restriction of maternal dietary glucose on lactational performance, pregnant dams were fed one of four isoenergetic diets containing graded levels of glucose (0, 12, 24 and 60%) from d 2 of pregnancy to d 15 of lactation. Dams fed the 0% glucose diet produced colostrum with higher protein and lower lactose and fat concentrations than normal, but all pups born to these dams failed to survive more than 24 h postpartum. Dams fed glucose-restricted diets (12 and 24%) had significantly lower d 15 milk fat concentration than dams fed the control diet, but there were no differences in milk protein, lactose and glucose concentrations. On d 15, pups suckling dams fed the 12% glucose diet had significantly lower body weights than pups of dams fed 24 and 60% glucose diets. Restriction of dietary glucose to 12% resulted in significantly smaller mammary gland cell size but failed to produce any significant differences in mammary gland composition (protein, fat and glycogen). The results indicate that the level of glucose in the maternal diet is an important determinant of milk composition and that > 24% glucose is needed for optimal milk fat concentration, whereas 12% dietary glucose is sufficient to sustain normal milk lactose concentration. The altered lactational performance in response to dietary glucose restriction was not mediated through changes in mammary gland composition, but in part by the reduced mammary gland size.

Zinc deficiency impairs immune responses against parasitic nematode infections at intestinal and systemic sites.

Research on the complex interactions among host nutritional status, parasitic infection and immune responsiveness has focused on the detrimental consequences of parasitic infections on host nutritional status and on mechanisms by which malnutrition impairs immunocompetence. Curiously, relatively few studies have examined the effects of malnutrition on the immune response in the parasite-infected host, and even fewer have considered the events occurring at the intestinal level, where absorption of nutrients occurs, intestinal parasites reside, and the gastrointestinal-associated lymphoid tissues play a role in directing both the local and the more systemic immune responses. Our work using a zinc-deficient nematode-infected mouse model reveals that parasites are better able to survive in the zinc-deficient hosts than in well-nourished hosts; that the production of interleukin-4 in the spleen of zinc-deficient mice is depressed, leading to depressed levels of IgE, IgG(1) and eosinophils; and that the function of T cells and antigen-presenting cells is impaired by zinc deficiency as well as by energy restriction. Given the paramount role of the gastrointestinal-associated lymphoid tissues in inducing and regulating immune responses to intestinal parasites and in orchestrating responses in the spleen and peripheral circulation, we conclude that zinc deficiency (in association with energy restriction) exerts profound effects on the gut mucosal immune system, leading to changes in systemically disseminated immune responses and, importantly, to prolonged parasite survival.