Effect of diet during pregnancy and lactation on the activity of HMG-CoA reductase in the developing rat

Wistar rats were fed a control diet or a diet containing either cholestyramine or high fat and cholesterol throughout gestation and the first 14 d of lactation. New-born litters were cross-fostered from rats fed the control diet to rats fed either cholestyramine or high fat and cholesterol, or from rats fed cholestyramine to rats fed the control diet. Hepatic hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase activity, plasma cholesterol and triglycerides were assayed on gestation d 20 and postnatal d 8, 14, 22 and 30. Cholestyramine had no effect on maternal or fetal plasma lipid levels but increased fetal hepatic HMG-CoA reductase activity by approximately 50%. The increased reductase activity persisted on postnatal d 8 and 14. Control pups suckled by dams fed cholestyramine also had significantly increased HMG-CoA reductase activities on postnatal d 8 and 14. The high fat and cholesterol diet significantly increased maternal plasma cholesterol but had no effect on HMG-CoA reductase activity in the fetus or suckling pups. Neither cholestyramine nor high fat and cholesterol altered the rat milk cholesterol levels. The studies demonstrate that HMG-CoA reductase activity in the developing rat can be altered by factors dependent on maternal diet. They do not support a hypothesis for regulation by maternal dietary or milk cholesterol supply.     

The effects of maternal protein deprivation on renal development and function in neonatal rats

This study was undertaken to investigate the effects of pre- and/or postnatal maternal protein deprivation (PD) on renal functional development in the offspring. Pregnant rats were fed either a control (24% protein) or low (8 or 10%) protein diet during gestation and lactation. Progeny of these dams were cross-fostered at birth, yielding four experimental groups: pups born of control dams and nursed by PD or control dams and pups born of PD dams and nursed by control or PD dams. While the effects of prenatal PD on body and kidney growth were negligible, PD during the nursing period appeared to have a more profound effect on body and kidney weight. Renal transport functions, quantified in vitro, were differentially affected by these dietary manipulations. Renal transport capacity for organic acids and bases was depressed in pups nursed by PD dams. Maturation of the renal organic acid transport system was also delayed in these pups. alpha-Aminoisobutyric acid accumulation by renal cortical slices was enhanced only in 10-day old rats stressed by pre- and postnatal maternal PD. Renal gluconeogenic and ammoniagenic capacity was not impaired by these dietary manipulations. No differences in protein or water content of renal cortical slices were observed.     

Diets containing Sophora japonica L. prevent weight gain in high-fat diet-induced obese mice

Obesity, a worldwide epidemic, is associated with metabolic diseases such as insulin resistance, dyslipidemia, hypertension, and heart disease. Many strategies, including natural alternative antiobesity agents, have been widely used to prevent obesity. Polyphenolic compounds and flavonoids from natural products are shown to inhibit adipogenesis. Because mature fruits of Sophora japonica L. were previously shown to contain antiadipogenic compounds, we hypothesized that diets with mature fruits of S japonica L. would prevent body weight gain in high-fat diet–induced obesity. Four-week-old mice were fed either a control high-fat diet, or high-fat diet containing 1% or 5% of S japonica L. for 4 weeks. The administration of S japonica L. fed in combination with a 30% high-fat diet significantly decreased body weight gain. S japonica L. also reduced serum and hepatic triglyceride, serum total, and high-density lipoprotein cholesterol. Consistent with the effects of lowering glucose level and fat mass, S japonica L. caused a decrease in the number of large adipocytes and a concomitant increase in the number of small adipocytes, which may explain at least in part the antiobesity effects of S japonica L. Together, these data provide evidence for roles of S japonica L. in the control of body weight and obesity-related metabolic diseases.     

D-核糖对高脂喂饲小鼠胰岛素抵抗的影响

目的观察D-核糖对高脂喂饲的C57BL/6小鼠血糖、血脂及胰岛素等的影响,探讨D-核糖对改善高脂膳食引起的糖耐量异常和胰岛素抵抗的可能性。方法 8 w龄C57BL/6雄性小鼠36只,随机分成正常对照、高脂对照、低剂量的D-核糖+高脂组(高脂+2.5%核糖)和高剂量的D-核糖+高脂组(高脂+5%核糖),喂饲12 w,记录摄食量和体重变化。11w进行葡萄糖耐量试验(OGTT),并计算葡萄糖曲线下面积(AUC)。干预12w处死,进行血生化指标及胰岛素检测。结果高脂+5%核糖组小鼠的血糖水平低于高脂对照组(P<0.05);高脂+2.5%核糖和高脂+5%核糖组糖耐量曲线下面积(P<0.01)、血清胰岛素水平(P<0.05)及胰岛素抵抗指数HOMA-IR(P<0.01)均显著低于高脂对照组。血清胆固醇(CHO)、高密度脂蛋白胆固醇(HDL-C)在核糖干预后的变化并不明显(P>0.05);高脂+5%核糖组血清低密度脂蛋白胆固醇(LDL-C)、血清甘油三酯(TG)及游离脂肪酸(FFA)低于高脂对照组(P<0.05)。结论 D-核糖可以改善高脂饲料喂饲小鼠的糖耐量异常和胰岛素抵抗。[营养学报,2013,35(2):142-145]     

Maternal fish oil supplementation ameliorates maternal high-fructose diet-induced dyslipidemia in neonatal mice with suppression of lipogenic gene expression in livers of postpartum mice

Maternal fructose consumption during pregnancy and lactation is associated with metabolic dysregulation in offspring. We tested the hypothesis that fish oil (FO) supplementation during pregnancy and lactation improves fructose-induced metabolic dysregulation in postpartum dams and offspring mice. We therefore aimed to determine the effects of FO supplementation on metabolic disruption in neonatal mice and dams induced by a maternal high-fructose diet (HFrD). The weight of the offspring of dams fed with HFrD on postnatal day 5 was significantly low, but this was reversed by adding FO to the maternal diet. Feeding dams with HFrD significantly increased plasma concentrations of triglycerides, uric acid, and total cholesterol, and decreased free fatty acid concentrations in offspring. Maternal supplementation with FO significantly suppressed HFrD-induced hypertriglyceridemia and hyperuricemia in the offspring. Maternal HFrD induced remarkable mRNA expression of the lipogenic genes Srebf1, Fasn, Acc1, Scd1, and Acly in the postpartum mouse liver without affecting hepatic and plasma lipid levels. Although expression levels of lipogenic genes were higher in the livers of postpartum dams than in those of nonmated mice, HFrD feeding increased the hepatic lipid accumulation in nonmated mice but not in postpartum dams. These findings suggest that although hepatic lipogenic activity is higher in postpartum dams than nonmated mice, the lipid consumption is enhanced in postpartum dams during pregnancy and lactation. Maternal FO supplementation obviously suppressed the expression of these lipogenic genes. These findings coincide with reduced plasma triglyceride concentrations in the offspring. Therefore, dietary FO apparently ameliorated maternal HFrD-induced dyslipidemia in offspring by suppressing maternal lipogenic gene expression and/or neonatal plasma levels of uric acid.     

Fetal programming of dietary fructose and saturated fat on hepatic quercetin glucuronidation in rats

ObjectivePhase II biotransformation of flavonoids generates bioactive metabolites in vivo. However, data on the effect of environmental and physiologic factors and fetal programming on phase II pathways toward flavonoids are limited. We examined the effect of parental exposure to a diet high in saturated fats and fructose 1 mo before conception through lactation on in vitro hepatic uridine 5′-diphosphate (UDP)-glucuronosyltransferase (UGT) activity toward quercetin in parent and offspring rats and the interaction between diet and sex.MethodsParents were fed a diet containing 9.9% coconut fat, 0.5% cholesterol, 30% fructose, and 30% glucose (SFF) or a control (C) diet containing 11% corn oil and 60% glucose. After weaning, offspring were fed the C diet for an additional 12 wk. The glucuronidation rate of microsomal UGT was determined with quercetin 30 μmol/L and 12.5 μg of protein in a total volume of 100 μL after a 15-min incubation at 37°C. Three quercetin glucuronides (7-O-quercetin glucuronide, 4′-O-quercetin glucuronide, and 3′-O-quercetin glucuronide) were quantified.ResultsIn the parent females, the SFF diet decreased by 29% and 19% the production rate of 3′- and 4′-O-quercetin glucuronide quercetin glucuronides, respectively, compared with the C diet (P ≤ 0.05). The production rate of 7-O-quercetin glucuronide quercetin glucuronide in the female offspring rats born to C dams was 59% larger than in their male counterparts (P < 0.05), but no difference was observed in the offspring of SFF dams.ConclusionHigh dietary fructose and saturated fat decreased UGT capacity toward quercetin in female rats and in utero exposure to the diet decreased the glucuronidation capacity of their pups.     

The role of liquid diet formulation in the postnatal ethanol exposure of rats via mother's milk

The nutritional adequacy of three liquid diets containing ethanol to support lactation was studied in rats. Diets 1 and 2 provided 18 and 25% kcal, respectively, as protein with 36% of total calories as ethanol, while in diet 3 alcohol provided 28% and protein 25% of total calories. Three series of isoenergetically pair-fed rats, as well as an ad libitum group fed a solid diet, were studied. A primary maternal malnutrition was evident in rats fed diet 1. With respect to diet 2, the 96% postnatal mortality which occurred may have been due to an inhibition of milk production mediated by exaggerated blood alcohol concentrations present in the lactating dams. Diet 3 seemed to be nutritionally adequate for the extra requirements for lactation and a direct effect of ethanol was observed in the sucklings. High blood alcohol levels (25-50 mmol/1) were obtained in dams fed ethanol diets 1 and 3; however only 1% of maternal blood alcohol appeared in the blood of sucklings, demonstrating a low transfer of ethanol from mother to offspring through the milk. Finally the model for postnatal exposure to alcohol via mother's milk is discussed in terms of other indirect alcohol-related factors which make it difficult to evaluate the direct impact of ethanol per se in the normal development of the suckling pups.     

Maternal micronutrient supplementation suppresses T cell chemokine receptor expression and function in F1 mice

Prenatal environmental exposures play a critical role in determining late-life chronic disease susceptibility. However, the mechanisms linking the in utero environment and disease development in the offspring are poorly understood. Recent investigations have confirmed a central pathogenic role of T cell chemokine receptors, particularly C-C chemokine receptor (CCR) 2 and CCR5, in chronic inflammatory conditions. This study was designed to determine the effect of a synthetic prenatal micronutrient supplementation (MS) diet rich in methionine pathway metabolites on the T cell chemokine system in F1 C57Bl/6 mice. Female mice were fed either an MS or control diet 3 wk prior to mating, during pregnancy, and lactation. At 4 wk of age, F1 mice were killed for experiments or were fed the standard NIH-31 diet and allowed to age. Food consumption, maternal weight gain, and litter size were similar in dams fed the control and MS diets. However, the F1 offspring of dams fed the MS diet were smaller in size (P < 0.001). T cells from the MS F1 offspring had global hypermethylation compared with control F1 offspring (P < 0.005), corresponding to lower T cell chemokine receptor expression [CCR2 (P < 0.001), CCR5 (P < 0.001), and C-x-C chemokine receptor 3 (P < 0.01)] and cytokine expression [TNFα (P < 0.05), IL-2 (P < 0.001), and IL-4 (P < 0.01)]. Reduced T cell chemokine receptor gene expression in MS F1 mice was associated with decreased chemotaxis in vitro to C-C chemokine ligand (CCL) 2 and C-X-C chemokine ligand 10 (P < 0.01) and in vivo to CCL2 (P < 0.01). Taken together, the results suggest that epigenetic alteration through prenatal diet manipulation reduces the response to proinflammatory signals in mice.     

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.     

Altered lactational performance in rats fed low carbohydrate diets and its effect on growth of neonatal rat pups

The possibility that low carbohydrate diets fed to nursing rat dams altered milk composition and impaired neonatal growth and development was explored. Pregnant control dams fed a 62% glucose diet were paired at parturition with experimental dams fed diets with either severe (0% glucose) or moderate (6% glucose) carbohydrate restriction. At birth half of the littermates of each pair were cross-fostered so that each dam nursed a litter consisting of one-half deficient and one-half control pups. All pups born to dams fed the 0% glucose diet died within 24 h of birth whether they were nursed by control or deficient dams. Control pups cross-fostered to these deficient dams died by the second day; the 0% glucose diet failed to support milk production. In contrast, the dams fed the 6% glucose diet produced milk, but its composition was significantly lower in carbohydrate and lipid than was milk of control dams. This altered milk composition was associated with retarded postnatal growth and development. Control pups cross-fostered to 6% glucose dams showed decreased survival (83% vs. 97%) and significantly reduced body weight (10 g vs. 12 g) at d 7. Conversely, 6% glucose pups cross-fostered to control dams showed improved survival (54% vs. 29%) and significantly increased body weight (9 g vs. 7 g) at d 7. These data showed that carbohydrate-restricted diets altered milk production and/or composition, which, in turn, reduced growth and increased mortality in the pups nursed by dams fed these diets. The results demonstrate that an adequate source of dietary carbohydrate is important for optimal lactational performance.     

Effect of maternal carbohydrate intake on mitochondrial activity and on lipogenesis by the young and mature progeny

The influence of maternal dietary sucrose on lipogenesis and on oxygen consumption and ATP production by isolated hepatic mitochondria was studied. During gestation and lactation, female BHE rats were fed either a 65% starch or a 65% sucrose diet. At weaning, male progeny were fed either the diet of their dam or the alternate diet. Rates of oxygen consumption and ATP production from isolated hepatic mitochondria, rates of 3H incorporation into fatty acids, and percent liver lipid were determined at 50 and 150 days of age. Correlation coefficients between mitochondrial function and hepatic lipogenic activity were calculated. Analysis of variance of these data indicated that state IV oxygen consumption was influenced by age and by an interaction of the maternal diet and the diet fed the progeny from weaning. The respiratory control ratio was influenced by the interaction of the maternal diet and the diet fed the progeny and by the interaction of the maternal diet and the age of the progeny when killed. ATP synthesis and recovery of ADP as ATP was influenced by an interaction of all three variables: maternal diet, growth diet and age. In progeny killed at 150 (but not 50) days of age, sucrose feeding increased the incorporation of tritium into fatty acids. Liver lipid levels were influenced by age and diet. Mitochondrial ATP synthesis was negatively correlated with hepatic lipid content, and mitochondrial ATP recovery from ADP was negatively correlated with 3H incorporation and percent liver lipid. These results suggest that alterations in hepatic mitochondrial ATP production may be associated with the increase in hepatic lipid synthesis and serum lipid levels frequently observed in sucrose-fed animals as they age.     

Lowering serum cholesterol level by feeding a 40% ethanol-eluted fraction from HP-20 resin treated with hot water extract of adzuki beans (Vigna angularis) to rats fed a high-fat cholesterol diet

ObjectiveHot water extract of adzuki beans (Vigna angularis) was subjected to HP-20 resin chromatography. The fraction eluted from the column using 40% ethanol (EtEx.40) was investigated by its effect on serum lipids in rats fed a high-fat cholesterol and/or cholesterol-free high-fat diet.MethodsThe rats were divided into 4 groups. Groups 1 and 2 were fed a high-fat cholesterol diet with or without 3.5% EtEx.40 for 2 wk. Group 3s and 4 were fed a high-fat cholesterol-free diet with or without 3.5% EtEx.40 for 2 wk.ResultsIn the high-fat-cholesterol diet groups, there was no significant difference in food intake in the experimental diet group when compared with the control group. Serum total cholesterol level was significantly decreased in the rats fed the EtEx.40 diet, but there was no difference in fecal excretion of cholesterol and bile acid between the two dietary groups. Conversely, in the high-fat cholesterol-free diet groups, ingestion of EtEx.40 reduced serum triacylglycerol concentration.ConclusionIngestion of EtEx.40 suppressed serum cholesterol level in rats fed the high-fat cholesterol and serum triacylglycerol level in rats fed the high-fat cholesterol-free diet. These mechanisms did not become clear in this experiment.     

Effects of riboflavin repletion during different developmental phases on behavioral patterns, brain nucleic acid and protein contents, and erythrocyte glutathione reductase activity of male rats.

Effects of riboflavin repletion of rats at various stages of development were evaluated by biochemical and behavioral parameters. One group of dams received diets containing a suboptimal level of riboflavin, approximately 15 mug, and another group, control, received approximately 40 mug of the vitamin daily 2 weeks before mating. Rats fed the control diet received approximately 120 mug riboflavin daily during pregnancy and lactation; suboptimals received approximately 15 mug daily. Some rats fed the control diet were pair-fed to rats fed the suboptimal ration. A group of dams fed the suboptimal diet was switched to control after parturition. At weaning, male offspring were fed the same riboflavin levels their respective dams received before mating except one group, whose dams were fed the suboptimal diet, received the control diet. Male progeny of dams pair-fed the control diet to suboptimal rats were either pair-fed to offspring of suboptimal dams or to offspring riboflavin-repleted at weaning. Rats that always received the suboptimal diet had significantly higher general activity scores at 60 days of age than the scores of other animals. Brains from rats always fed the suboptimal diet and those receiving riboflavin repletion at weaning had lower, sometimes significantly, DNA, RNA, and protein contents than those from other animals. Riboflavin restriction during gestation and lactation, but not gestation alone, appeared to produce permanent alterations in general activity scores and brain nucleic acid and protein contents of male rat progeny.     

Overweight induced by high-fat diet delays rat cutaneous wound healing

Prolonged wound healing is a complication that contributes to morbidity and mortality. Overweight people regularly undergo surgery and trauma, and often develop chronic wounds, but the effects of the adipose tissue excess on cutaneous wound healing are not well understood. This study tested the hypothesis that overweight induced by a high-fat diet impairs rat cutaneous wound healing. Male Wistar rats were fed with either a high-fat or a standard (control) diet. After 15 weeks, an excisional lesion was done and the animals were killed 21 d later. Wound contraction and re-epithelialization, blood pressure, glucose and retroperitoneal fat were evaluated. After killing, lesion and adjacent normal skin were formol-fixed and paraffin-embedded. Inflammatory infiltrate, myofibroblasts, collagen fibres and cellular proliferation were analysed and blood vessels were evaluated using stereological methods. There was no difference in blood pressure and glucose, but retroperitoneal fat increased in the high-fat diet group. Animals fed with the high-fat diet presented delayed wound contraction and re-epithelialization. It was found that 21 d after wounding, overweight induced by a high-fat diet increased the inflammatory infiltrate and delayed myofibroblastic differentiation, collagen deposition, epithelial and connective tissue cell proliferation, and angiogenesis. These findings support the hypothesis that a high-fat diet exerts negative effects on rat cutaneous wound healing, due mainly to the prolongation of the inflammatory phase.     

Effects of maternal iron restriction in the rat on hypoxia-induced gene expression and fetal metabolite levels

The mechanism by which maternal Fe deficiency in the rat causes fetal growth retardation has not been clearly established. This study compared the effects on the fetuses from dams fed a control diet with two groups of dams fed Fe-restricted diets. One Fe-restricted group was fed the Fe-restricted diet for 1 week prior to mating and throughout gestation and the second Fe-restricted group was fed the Fe-restricted diet for 2 weeks prior to mating and throughout gestation. On day 21 of gestation Fe-restricted dams, and their fetuses, were anaemic. Fetal weight was reduced in both Fe-restricted groups compared with controls. Expression of hypoxia-inducible factor (HIF)-1alpha and vascular endothelial growth factor (VEGF) are induced by hypoxia. The levels of HIF-1alpha mRNA were highest in placenta, then in kidney, heart and liver but were not different between the groups. Levels of plasma VEGF were not different between the groups. Maternal plasma triacylglycerol was decreased in the 1-week Fe-restricted dams compared with controls. Maternal plasma cholesterol and free fatty acid levels were not different between the groups. In fetal plasma, levels of triacylglycerol and cholesterol were decreased in both Fe-restricted groups. In maternal plasma, levels of a number of amino acids were elevated in both Fe-restricted groups. In contrast, levels of a number of amino acids in fetal plasma were lower in both Fe-restricted groups. Fetal plasma lactate was increased in Fe-restricted fetuses but fetal plasma glucose and beta-hydroxybutyrate were not affected. These changes in fetal metabolism may contribute to fetal growth retardation in this model. This study does not support the hypothesis that the Fe-restricted fetus is hypoxic.     

Low arachidonic acid rather than alpha-tocopherol is responsible for the delayed postnatal development in offspring of rats fed fish oil instead of olive oil during pregnancy and lactation

This study was designed to compare in rats the effects of dietary fish oil and olive oil during pregnancy and lactation on offspring development, fatty acid profile and vitamin E concentration. From d 0 of pregnancy, female Sprague-Dawley rats were divided into two groups that were fed purified diets that differed only in their nonvitamin lipid components. One diet contained 10 g fish oil/100 g diet (FOD), whereas the other contained 10 g olive oil/100 g diet (OOD). At d 20 of gestation, maternal adipose tissue fatty acid profile did not differ between rats fed the two diets, whereas both maternal and fetal plasma and liver arachidonic acid (AA) contents were proportionally lower and eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid contents were higher in the FOD group than in the OOD group. alpha-Tocopherol concentration was lower in maternal and fetal plasma, liver and brain in the FOD group than in the OOD group. The postnatal increase in body weight and length was less and body and psychomotor maturation indices were delayed in pups from FOD-fed dams compared with those from OOD-fed dams. This difference was maintained when pups were cross-fostered at birth, with the delay in postnatal development present in the pups suckling dams fed FOD during lactation. At age 21 d, pups suckling dams fed FOD had lower AA and higher EPA and DHA concentrations in brain phospholipids. Although alpha-tocopherol in plasma and liver was lower in pups suckling dams fed FOD rather than OOD, brain alpha-tocopherol concentrations did not differ. Milk yield and milk alpha-tocopherol and AA concentrations were lower and EPA and DHA were higher in the milk of dams fed FOD compared with those fed OOD. Postnatal development indices and the proportion of plasma, liver and brain AA concentrations, although not plasma, liver and brain alpha-tocopherol concentrations, recovered to the values found in dams fed OOD when the FOD was supplemented with gamma-linolenic acid. However, postnatal development indices were not recovered when the FOD was supplemented with sufficient exogenous vitamin E to increase plasma and liver alpha-tocopherol concentrations above those in dams fed OOD. Thus, although feeding FOD during pregnancy and lactation decreases both alpha-tocopherol and AA concentrations, the latter deficiency rather than the former seems to be responsible for delayed postnatal development of rat pups.     

High Maternal Omega-3 Supplementation Dysregulates Body Weight and Leptin in Newborn Male and Female Rats: Implications for Hypothalamic Developmental Programming

Maternal diet is critical for offspring development and long-term health. Here we investigated the effects of a poor maternal diet pre-conception and during pregnancy on metabolic outcomes and the developing hypothalamus in male and female offspring at birth. We hypothesised that offspring born to dams fed a diet high in fat and sugar (HFSD) peri-pregnancy will have disrupted metabolic outcomes. We also determined if these HFSD-related effects could be reversed by a shift to a healthier diet post-conception, in particular to a diet high in omega-3 polyunsaturated fatty acids (ω3 PUFAs), since ω3 PUFAs are considered essential for normal neurodevelopment. Unexpectedly, our data show that there are minimal negative effects of maternal HFSD on newborn pups. On the other hand, consumption of an ω3-replete diet during pregnancy altered several developmental parameters. As such, pups born to high-ω3-fed dams weighed less for their length, had reduced circulating leptin, and also displayed sex-specific disruption in the expression of hypothalamic neuropeptides. Collectively, our study shows that maternal intake of a diet rich in ω3 PUFAs during pregnancy may be detrimental for some metabolic developmental outcomes in the offspring. These data indicate the importance of a balanced dietary intake in pregnancy and highlight the need for further research into the impact of maternal ω3 intake on offspring development and long-term health.     

Influence of maternal cholestyramine treatment on cholesterol and bile acid metabolism in adult offspring

To reduce ileal reabsorption of bile acids and to deplete hepatic cholesterol pools, female rats were fed a diet containing 5% (wt/wt) cholestyramine from 4 days prior to mating. Control rats were fed the same diet without cholestyramine. In one group on day 20 of gestation diet-fed dams and their fetuses were investigated. Additional pups were raised in litters of eight and nursed by their mothers for 30 days at which time they were weaned to the control diet. All dams were given the control diet from day 14 of lactation; at no time did neonates have access to cholestyramine. Offspring were raised until 3 months of age then fed the control, cholestyramine or a high fat, high cholesterol diet for 5 days. Maternal cholestyramine produced significant elevation of fetal hepatic 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase; fetal 7 alpha-hydroxylase (7 alpha-OH) activity, plasma cholesterol and triglyceride levels, however, were not significantly altered. The elevated HMG-CoA reductase activity persisted in liver and in addition was present in jejunum of 3-month-old male offspring challenged with the control or cholestyramine diet for 5 days. When challenged with the high fat, high cholesterol diet, male offspring from cholestyramine-treated dams had significantly higher plasma cholesterol levels but HMG-CoA reductase and 7 alpha-OH activity similar to controls. Maternal treatment had no apparent effect on plasma triglyceride or hepatic 7 alpha-OH in 3-month-old male offspring.(ABSTRACT TRUNCATED AT 250 WORDS)