Dietary Fibre,Coronary Heart Disease and Diabetes Mellitus

Maternal nutrition has been identified as a factor determining fetal growth and risk of adult disease. In rats, the feeding of a low protein diet during pregnancy retards fetal growth and induces hypertension in the resulting offspring. Rat models of low protein feeding have been extensively used to study the mechanisms that may link maternal nutrition with impaired fetal growth and later cardiovascular disease and diabetes. Low protein diets of differing composition used in different laboratories have yielded inconsistent data on the relationship between maternal protein intake and offsprings' blood pressure. Two separate low protein diet protocols were compared in terms of their ability to programme hypertension during fetal life. Pregnant rats were assigned to receive one of four diets. Two diets were obtained from a commercial supplier and provided casein at 22 or 9% by weight (H22, control; H9, low protein). The other two diets, manufactured in our own facility, provided 18% casein (S18, control) or 9% casein (S9, low protein) by weight. The diets differed principally in their overall fat content, fatty acid composition, methionine content and the source of carbohydrate. Feeding of the experimental diets commenced on the first day of pregnancy and continued until the rats delivered their litters. Following weaning all the offspring had blood pressure determined on a single occasion. Both low protein diets reduced maternal weight gain relative to their corresponding control diets. Despite this litter sizes were unaffected by the dietary protocols. Both low protein diets reduced birthweights of the pups. Systolic blood pressure was significantly elevated in the offspring of rats fed a low protein S9 diet relative to all other groups (P < 0.05). Animals exposed to H9 diet in utero had similar blood pressures to their H22 controls. It is concluded from this work that differing low protein diet manipulations in rat pregnancy elicit different programming effects upon the developing cardiovasculature. The balance of protein and other nutrients may be a critical determinant of the long-term health effects of maternal undernutrition in pregnancy.     

Critical differences between two low protein diet protocols in the programming of hypertension in the rat

Maternal nutrition has been identified as a factor determining fetal growth and risk of adult disease. In rats, the feeding of a low protein diet during pregnancy retards fetal growth and induces hypertension in the resulting offspring. Rat models of low protein feeding have been extensively used to study the mechanisms that may link maternal nutrition with impaired fetal growth and later cardiovascular disease and diabetes. Low protein diets of differing composition used in different laboratories have yielded inconsistent data on the relationship between maternal protein intake and offsprings' blood pressure. Two separate low protein diet protocols were compared in terms of their ability to programme hypertension during fetal life. Pregnant rats were assigned to receive one of four diets. Two diets were obtained from a commercial supplier and provided casein at 22 or 9% by weight (H22, control; H9, low protein). The other two diets, manufactured in our own facility, provided 18% casein (S18, control) or 9% casein (S9, low protein) by weight. The diets differed principally in their overall fat content, fatty acid composition, methionine content and the source of carbohydrate. Feeding of the experimental diets commenced on the first day of pregnancy and continued until the rats delivered their litters. Following weaning all the offspring had blood pressure determined on a single occasion. Both low protein diets reduced maternal weight gain relative to their corresponding control diets. Despite this litter sizes were unaffected by the dietary protocols. Both low protein diets reduced birthweights of the pups. Systolic blood pressure was significantly elevated in the offspring of rats fed a low protein S9 diet relative to all other groups (P < 0.05). Animals exposed to H9 diet in utero had similar blood pressures to their H22 controls. It is concluded from this work that differing low protein diet manipulations in rat pregnancy elicit different programming effects upon the developing cardiovasculature. The balance of protein and other nutrients may be a critical determinant of the long-term health effects of maternal undernutrition in pregnancy.     

Gestational protein restriction induces a reduced number of glomeruli in the young

In order to study the effect of low protein content in maternal diet on kidney development of pups, Wistar female rats were fed isocaloric diets containing 4%, 8% or 20% protein throughout pregnancy and transferred to a commercial diet during lactation. Birth weight of pups was significantly lower (p < 0.05) only when mothers were fed 4% protein diet. Offspring of the 3 groups of dams were weaned on the 21^st day and sacrificed 7 days later. Significant reduction (p < 0.05) in the number of glomeruli but not in their diameter, glomerular sclerosis index or interstitial fibrosis index were found in the pups born to mothers fed both low protein diets. Plasma creatinine was significantly higher (p < 0.05) in offspring of both low protein diets, while homocysteine only in that born to the 4% protein fed mothers. So, our results are consistent with the hypothesis that maternal undernutrition can determine a reduction in nephron number and hence influence adult cardiovascular and renal diseases.     

Effects of geophagia (kaolin ingestion) on the maternal blood and embryonic development in the pregnant rat

Geophagia, in the form of clay-eating, is often observed during pregnancy in the human population. The intent of this study was to determine the effects of kaolin (clay) ingestion on the maternal blood and embryonic development of the pregnant rat. Thirty-six Sprague-dawley female rats were divided into three groups: control diet, 20% kaolin diet, and iron-supplemented 20% kaolin diet. The diets were fed 37 to 68 days, 69 to 95 days, and 96 to 117 days prior to fertilization, and the same diets were fed for the duration of the gestation period. The rats fed the kaolin diet exhibited significant reductions in hemoglobin, hematocrit, and red blood cell levels, thus indicating maternal anemia. There was also a significant reduction in the birth weight of the pups born to kaolin fed rats. The kaolin fed rats receiving an iron supplement maintained hematocrit, hemoglobin, red blood cell levels, and pup weight within the normal range.     

Maternal protein restriction during pregnancy and lactation in rats imprints long-term reduction in hepatic lipid content selectively in the male offspring

Maternal protein restriction during pregnancy and lactation reduces whole body lipid stores and alters lipid homeostasis in the adult offspring. Lipid homeostasis in the body is regulated, in part, by the liver via the metabolic processes of synthesis and utilization of lipids. The present study tested the hypothesis that maternal protein restriction will imprint changes in hepatic lipid metabolism and thereby alter the hepatic lipid content of the adult offspring. Pregnant rats were fed purified diets containing 19% protein (control group) or 8% protein (low-protein group) throughout pregnancy and lactation. On day 28, pups from both groups were weaned onto regular laboratory chow. On days 65 and 150, male and female pups from each litter in both groups were killed and blood and liver collected. Maternal protein restriction was found to reduce birth weight and produce long-term reduction in the body weight of the offspring. On day 65, liver triglyceride content was decreased by 40% in the male offspring that were fed a low-protein diet. The reduction in liver triglyceride content persisted until day 150, at which time it was accompanied by decreases in hepatic cholesterol content. No such changes were observed in the female offspring. To determine if the alterations in liver lipid content resulted in compensatory changes in liver carbohydrate stores, hepatic glycogen content was measured in male offspring. Hepatic glycogen content was similar between the 2 groups on days 65 and 150. In conclusion, the present study in rats showed that maternal protein restriction during pregnancy and lactation imprints long-term changes in hepatic lipid content selectively in the male offspring.     

Prenatal programming of angiotensin II type 2 receptor expression in the rat

Exposure to undernutrition during fetal life has been proposed as an underlying cause of adult hypertension. Epidemiological studies demonstrating relationships between low birth weight and later CVD are supported by animal experiments indicating that manipulations of the maternal diet in pregnancy exert programming effects upon blood pressure control. Pregnant female Wistar rats were fed a control diet (n 13) or a low-protein diet (n 12) throughout pregnancy. At delivery all animals were fed the same standard laboratory chow diet. Analysis of nephron number in kidneys obtained from 4-week-old offspring showed that this was significantly (P<0.05) reduced in animals exposed to maternal protein restriction. At this age rats exposed to low-protein diets in utero had systolic blood pressures that were significantly greater than those of control animals (+23 mmHg, P<0.05). Administration of ascending doses of angiotensin II (1-40 ng/kg body weight intravenously) to 10-week-old anaesthetised female rats showed that the pressor response to the peptide was greater and more prolonged in animals exposed to low-protein diets in utero. Renal expression of mRNA for the angiotensin II type 1A receptor was similar in the two groups of rats, but low-protein-exposed animals had significantly lower renal expression of the type 2 receptor (P=0.023). These results suggest that maternal nutritional status programmes expression of the renal angiotensin II type 2 receptor. This may play a key role in the impairment of renal development and the elevation of blood pressure noted in rats exposed to intra-uterine protein restriction.     

Evidence of progressive deterioration of renal function in rats exposed to a maternal low-protein diet in utero

Intrauterine growth retardation associated with maternal undernutrition is proposed to play a significant role in the aetiology of hypertension and CHD. Animal experiments suggest that the kidney, which is extremely vulnerable to the adverse effects of growth-retarding factors, may play an important role in the prenatal programming of hypertension. Maintenance of renal haemodynamic functions following structural impairment in fetal life is proposed to require adaptations which raise systemic blood pressure and promote a more rapid progression to renal failure. Rats were fed on diets containing 180 g casein/kg (control) or 90 g casein/kg (low protein) during pregnancy. The offspring were studied in terms of blood pressure, creatinine clearance, blood urea N, plasma and urinary albumin, renal morphometry and metabolic activity at 4, 12 and 20 weeks of age. Blood pressure was elevated at all ages in the low-protein-exposed offspring, relative to control rats. Rats (4 weeks old) exposed to the low-protein diet had smaller kidneys which were shorter and wider than those of control animals. Creatinine clearance was significantly reduced in 4-week-old rats exposed to the low-protein diet. Renal morphometry and creatinine clearance at older ages were not influenced by prenatal diet. Blood urea N, urinary output and urinary albumin excretion were, however, significantly greater in low-protein-exposed rats than in control rats at 20 weeks of age. These findings are suggestive of a progressive deterioration of renal function in hypertensive rats exposed to mild maternal protein restriction during fetal life. This is consistent with the hypothesis that adaptations to maintain renal haemodynamic functions following impairment of fetal nephrogenesis result in an accelerated progression towards glomerulosclerosis and increased intrarenal pressures mediated by rising vascular resistance.     

Intergenerational programming of impaired nephrogenesis and hypertension in rats following maternal protein restriction during pregnancy

Associations between birth weight and CVD in adult life are supported by experiments showing that undernutrition in fetal life programmes blood pressure. In rats, the feeding of a maternal low-protein (MLP) diet during gestation programmes hypertension. The present study aimed to assess the potential for a nutritional insult to impact across several generations. Pregnant female Wistar (F0) rats were fed a control (CON; n 10) or MLP (n 10) diet throughout gestation. At delivery all animals were fed a standard laboratory chow diet. At 10 weeks of age, F1 generation offspring were mated to produce a second generation (F2) without any further dietary change. The same procedure produced an F3 generation. Blood pressure in all generations was determined at 4, 6 and 8 weeks of age and nephron number was determined at 10 weeks of age. F1 generation MLP-exposed offspring exhibited raised (P < 0.001) systolic blood pressure (male 143 (sem 4) mmHg; female 141 (sem 4) mmHg) compared with CON animals (male 132 (sem 3) mmHg; female 134 (sem 4) mmHg). Raised blood pressure and reduced nephron number was also noted in the F2 generation (P < 0.001) and this intergenerational transmission occurred via both the maternal and paternal lines, as all three possible offspring crosses (MLP x CON, CON x MLP and MLP x MLP) were hypertensive (132 (sem 3) mmHg) compared with CON animals (CON x CON; 123 (sem 2) mmHg). No effect was noted in the F3 generation. It is concluded that fetal protein restriction may play a critical role in determining blood pressure and overall disease risk in a subsequent generation.     

Maternal protein deficiency causes hypermethylation of DNA in the livers of rat fetuses

Maternal protein deficiency during pregnancy is associated with changes in glucose tolerance and hypertension in the offspring of rats. In this study the growth of rat fetuses was examined when the dams were fed diets containing 18% casein, 9% casein or 8% casein supplemented with threonine. The extra threonine was added to reverse the decrease in circulating threonine concentrations that occurs when pregnant rats are fed protein-deficient diets. The fetuses of the group fed the low protein diet supplemented with threonine were significantly smaller than those of the control group and not significantly different from those fed low protein. Homogenates prepared from the livers of dams fed the diet containing 9% casein oxidized threonine at approximately twice the rate of homogenates prepared from dams fed the diet containing 18% casein. We conclude that circulating levels of threonine fall as a consequence of an increase in the activity of the pathway that metabolizes homocysteine produced by the transulfuration of methionine. Serum homocysteine was unaffected in the dams fed low protein diets compared with controls, but was significantly greater in dams fed the low protein diet supplemented with threonine. Elevated levels of homocysteine are associated with changes in the methylation of DNA. The endogenous methylation of DNA was greater than that of controls in the livers of fetuses from dams fed the 9% protein diets and increased further when the diet was supplemented with threonine. Our results suggest that changes in methionine metabolism increase homocysteine production, which leads to changes in DNA methylation in the fetus. An increase in maternal homocysteine may compromise fetal development, leading to the onset of glucose intolerance and hypertension in adult life.     

Effect of maternal iron restriction during pregnancy on renal morphology in the adult rat offspring

In rats, maternal anaemia during pregnancy causes hypertension in the adult offspring, although the mechanism is unknown. The present study investigated the renal morphology of adult rats born to mothers who were Fe-deficient during pregnancy. Rats were fed either a control (153 mg Fe/kg diet, n 7) or low-Fe (3 mg/kg diet, n 6) diet from 1 week before mating and throughout gestation. At delivery, the Fe-restricted (IR) mothers were anaemic; the IR pups were also anaemic and growth-retarded at 2 d of age. At 3 and 16 months, systolic blood pressure in the IR offspring (163 (sem 4) and 151 (sem 4) mmHg respectively, n 13) was greater than in control animals (145 (sem 3) and 119 (sem 4) mmHg respectively, n 15, P<0.05). At post mortem at 18 months, there was no difference in kidney weight between treatment groups, although relative kidney weight as a fraction of body weight in the IR offspring was greater than in control animals (P<0.05). Glomerular number was lower in the IR offspring (11.4 (sem 1.1) per 4 mm(2), n 13) compared with control rats (14.8 (sem 0.7), n 15, P<0.05). Maternal treatment had no effect on glomerular size, but overall, female rats had smaller and more numerous glomeruli per unit area than male rats. When all animals were considered, inverse relationships were observed between glomerular number and glomerular size (r-0.73, n 28, P<0.05), and glomerular number and systolic blood pressure at both 3 months (r-0.42, n 28, P<0.05) and 16 months of age (r-0.64, n 28, P<0.05). Therefore, in rats, maternal Fe restriction causes hypertension in the adult offspring that may be due, in part, to a deficit in nephron number.     

Influence of Dietary Fats Upon Systolic Blood Pressure in the Rat

Studies were performed to determine whether feeding diets with differing fatty acid content and composition had an influence on systolic blood pressure in the rat. Weanling male rats were fed standard laboratory chow (2.9% fat in total), or synthetic diets (10% fat in total) containing fish oil, butter, coconut oil or corn oil, for 5 weeks. Coconut oil and butter diets were rich in saturated fatty acids, whilst fish oil and corn oil were rich in the n-3 and n-6 unsaturated fatty acids respectively. Systolic blood pressure was measured using an indirect tail-cuff method at the end of the feeding period, and compared to a group of weanling rats.

Feeding the different diets did not alter the growth of the rats, so all animals were of similar weights at the time of blood pressure determination. Control (chow fed) animals, at nine weeks of age, had higher systolic blood pressures than the weanling, baseline control group. Fish oil fed rats had similar pressures to the chow fed rats. Corn oil fed rats had significantly lower systolic pressures than the controls. The rats fed the diets rich in saturated fatty acids (butter and coconut oil) had significantly higher blood pressures than all other groups. Systolic blood pressure was found to be significantly related to the dietary intakes of saturated and unsaturated fatty acids. The dietary intake of linoleic acid was significantly higher in corn oil fed rats than in other groups. Systolic blood pressure was inversely related to linoleic acid intake. Feeding a diet rich in saturated fatty acids significantly increases blood pressure in the rat. A high intake of n-6 fatty acids, and in particular linoleic acid, appears to have a hypotensive effect. Prenatal exposure of the rats to a maternal low protein diet, abolished the hypertensive effects of the coconut oil diet and the hypotensive effect of the corn oil diet upon young adult females. The intrauterine environment may, therefore, be an important determinant of the effects of these fatty acids on blood pressure in later life.     

Long-term effect of green tea extract during lactation on AMPK expression in rat offspring exposed to fetal malnutrition

ObjectiveThe fetal and neonatal environments are important determinants of disease risk in adult life. The aim of this study was to determine whether maternal green tea extract (GTE) intake during lactation affects the expression and activity of adenosine monophosphate-activated protein kinase (AMPK) in the kidneys of male offspring of protein-restricted dams during gestation.MethodsPregnant Wistar rats were fed control (C) or low-protein diets (LP) during gestation. Following delivery, dams received a control or GTE-containing control diet during lactation as follows: C on control diet (CC), LP on control diet (LPC), LP on 0.12% GTE-containing control diet (LPL), or LP on 0.24% GTE-containing control diet (LPH). Some of the male pups from each dam were sacrificed at week 3, and the remaining male pups were fed a standard diet and sacrificed at week 30. Blood chemistry and expression levels of AMPKα, mammalian target of rapamycin (mTOR), and Akt in the kidneys of the male offspring were examined.ResultsThe level of phosphorylated AMPKα in the LPH group at week 3 was higher than that in the LPC group. At week 30, the protein levels of total and phosphorylated AMPK in the LPL and LPH groups were lower than those in the LPC group. The protein levels of mTOR and Akt at week 30 in the LPL and LPH groups were lower than those in the LPC group.ConclusionGTE intake during lactation modulates AMPK, Akt, and mTOR expression in the kidneys of the adult male offspring of dams fed a protein-restricted diet and may induce long-term alterations in the expressions of these proteins in the kidneys.     

Maternal dietary fat type influences the growth and fatty acid composition of newborn and weanling rats

To determine whether the long-term consumption of different amounts or types of fat by female rats affects the growth and development of their progeny, Wistar rats were fed from weaning either a low fat diet (4.5% by weight) or one of three high fat (32%) diets containing predominantly beef tallow (high saturated fat), corn oil (high polyunsaturated fat) or equal portions of tallow and corn oil (high mixed fat). Offspring were killed at birth or weaning. Weight of newborn pups was lower with maternal consumption of high polyunsaturated fat diets. Carcass composition of newborn pups and body weight of weanling rats was unaffected by maternal diet. The percentage of carcass lipid was greater in weanling rats from all high fat-fed dams. In both newborn pups and weanling rats, percent composition in carcass lipids of 16:0, 16:1 and 18:1 fatty acids generally decreased and 18:2 increased as the high fat maternal diet became more unsaturated. The consumption of diets high in polyunsaturated fatty acids prior to and throughout gestation thus seemed to have a transitory effect on reducing fetal growth in rats.     

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)     

孕哺期PM2.5和高脂饮食联合暴露对大鼠仔鼠血压、血脂、血糖的影响

目的 探讨孕哺期细颗粒物（fine particulate matter,PM2.5）和高脂饮食（high fat diet,HFD）联合暴露对大鼠仔鼠血压、血脂、空腹血糖的影响,观察生命早期同时暴露PM2.5和HFD对子代发育的影响。方法 成年SD大鼠按照雌雄2[DK]∶1进行交配,孕鼠随机分为对照组（CC组）、高脂饮食组（HFD组）、PM2.5低暴露组（L-PM2.5组）、PM2.5高暴露组（H-PM2.5组）、高脂饮食+PM2.5低暴露组（HFD+L-PM2.5组）和高脂饮食+PM2.5高暴露组（HFD+H-PM2.5组）。对照组和PM2.5低、高暴露组给予普通饲料,其余给予高脂饲料。PM2.5染毒采用细颗粒物在线浓缩和动物染毒系统,低、高暴露剂量分别设为室外大气PM2.5浓度的2倍和4倍。母鼠从孕0日开始染毒,每天5h,每周5d,直至仔鼠出生后第21d（Postnatal day,PND21）,记录仔鼠体长和尾长,测量仔鼠的血压、心率,检测空腹血糖、血清甘油三酯、胆固醇水平。结果 PND21雄鼠HFD组、HFD+L-PM2.5组、HFD+H-PM2.5组体长较CC组增加,PND21雌鼠HFD+L-PM2.5组尾长较L-PM2.5组增加（P<0.05）。析因分析显示,PM2.5（F=3.492,P<0.05）和HFD（F=4.346,P<0.05）均使雌鼠收缩压升高,二者不存在交互作用（P>0.05）;HFD使雄鼠收缩压（F=9.259）、舒张压（F=5.981）、平均动脉压（F=7.754）升高（P均<0.05）,HFD+H-PM2.5组雄鼠收缩压、舒张压、平均动脉压均高于CC组（P<0.05）,PM2.5和HFD不存在交互作用（P>0.05）。PM2.5、HFD使雌鼠（F值分别为13.346,32.277,P均<0.05）、雄鼠血清甘油三酯（F值分别为5.723,10.360,P均<0.05）均升高,HFD+H-PM2.5组雌雄仔鼠甘油三酯含量均高于CC组,两者对雌鼠的血清甘油三酯含量存在协同作用（F=8.651,P<0.05）,对雄鼠不存在交互作用（P>0.05）。各组仔鼠空腹血糖水平差异无统计学意义（P>0.05）。结论 PM2.5和HFD联合暴露能引起PND21仔鼠血压、血脂升高,二者对血压的影响不存在交互作用,对雌性仔鼠血脂的影响存在协同作用。PM2.5和HFD对血压的影响存在性别差异。     

Protein malnutrition during pregnancy alters maternal behavior and anxiety-like behavior in offspring

Objective: The aim of this study was to evaluate the effects of protein malnutrition during pregnancy on maternal behavior, on the early behavior in pups by ultrasonic vocalizations (USVs) emission, and on the behavior of offspring in adulthood in an elevated T-maze.

Methods: Pregnant female rats were fed a normal protein-powdered diet (22% casein; control) or a low-protein (hypoproteic) diet (6% casein; protein restriction) during the first 2 weeks of pregnancy. On the fifth postpartum day (PND5), the number of USV was rated. On PND7, maternal behavior was assessed. Male offspring in adulthood were evaluated for behavioral performance in an elevated T-maze.

Results: Our results demonstrated that a hypoproteic diet during early pregnancy increased the maternal behavior, increased the number of USV by pups, and reduced the inhibitory avoidance responses in an elevated T-maze during adulthood. In addition, there was a reduction in weight gain of rats during pregnancy and of offspring during lactation.

Conclusion: In conclusion, the data found in our study suggest that the increase in USV emitted by pups due to hypoproteic diet during pregnancy accentuated maternal behavior. In addition, an increase in maternal care promoted the reduction in anxiety-like behavior in adult male offspring.     

Effect of feeding lysine and threonine fortified bread during gestation and lactation on growth of the brain in rats.

First and second litter offspring brain development was studied following the feeding of bread, bread plus lysine, or bread plus lysine and threonine to rats during pregnancy and lactation. Results were compared with offspring brain growth following maternal consumption of a stock diet, 13% casein or 26% casein diet. Brain weight, protein and cellularity progressively increased as lysine and lysine plus threonine were added to the maternal bread diets. The bread plus lysine and threonine diet resulted in similar or higher total weight, protein and DNA values for all brain areas in comparison with results from the stock diet or 13% casein diet. The 26% casein diet resulted in greater brain weight, protein and DNA values in comparison to the bread, bread plus lysine, 13% casein, or stock diets. First litter pups whose mothers were fed the 26% casein diet, in comparison to the bread plus lysine and threonine diet, had higher or similar brain weight and DNA levels. For second litter pups, all values were similar for both diets with the exceptions of lower brain stem weight for 26% casein and lower cerebellum DNA for bread plus lysine and threonine.     

Effect of low carbohydrate diets during pregnancy on embryogenesis and fetal growth and development in rats

Effects in pregnant rats of feeding diets specifically deficient in carbohydrate were studied. The dietary nonprotein energy source was lipid, provided as intact fat (soybean oil) or a fatty acid mixture (edible oleic acid) or a combination of these. These diets provided 9.5% casein protein, which was shown to be minimally adequate in both the lipid-based experimental diets and the high carbohydrate control diet. The diets were fed from mating through d 21 of pregnancy, and pups were delivered by cesarean section. The soybean oil-based zero-carbohydrate diet supported embryogenesis and produced at term normal numbers of normal appearing pups of body weight lower than that of pups from the high carbohydrate control diet. In contrast, the oleic acid-based zero-carbohydrate diet failed to maintain pregnancy, indicating a requirement for carbohydrate or intact fat or both. To maintain pregnancy to term required both 5-10% intact fat and 4% carbohydrate as glucose or its equivalent amount of glycerol from lipid. From feeding graded levels of glucose in fatty acid based diets containing 5-10% intact fat as soybean oil, the carbohydrate requirement was found to be 6-8% glucose to sustain maternal food intake and weight gain and to produce normal fetal weight at term, and 12% glucose to provide approximately half the fetal liver glycogen levels in controls fed a high carbohydrate diet. These experiments have produced the first evidence of the quantitative requirement for carbohydrate for embryogenesis and fetal growth and development in the pregnant rat dam.     

Effects of food or nutrient restriction on milk vitamin A transfer and neonatal vitamin A stores in the rat

We have investigated the effects of maternal diets low in fat or protein, or restricted in total food intake on vitamin A transfer from the dam to her pups. When animals were fed on diets moderately restricted in fat or protein, minimal differences in milk, serum, and liver vitamin A concentrations were observed compared with animals fed on a control diet. In a second study, dams were fed on diets more severely restricted in protein, or fat, or both, or were fed on a control diet equal to 50% of the intake of control rats but containing an equal amount of vitamin A. The quantity of milk obtained from these more severely restricted dams' nipples or the pups' stomachs was greatly reduced; however, there were no differences in milk vitamin A concentration. Body-weight, liver weight, and total liver vitamin A stores of undernourished pups were just half those measured for control pups, although serum vitamin A and serum retinol-binding protein were nearly normal in concentration. We conclude that (a) moderate restrictions in fat or protein in the maternal diet are insufficient to affect transfer of vitamin A to the suckling pup; (b) further dietary restrictions could cause decreased milk production with little change in milk vitamin A concentration and, hence, (c) the neonates' hepatic retinol accumulation during the suckling period is markedly reduced when maternal diets are severely deficient in fat or protein or of normal composition but restricted in amount.     

A low-protein isocaloric diet during gestation affects brain development and alters permanently cerebral cortex blood vessels in rat offspring.

In humans, low birth weight is associated with nonfatal stroke, cardiovascular disease and diabetes at adulthood. The aim of this study was to investigate in rats the effect of early protein restriction, inducing low birth weight, on brain and endocrine pancreas vascularization at birth and to study if such alterations lasted until adulthood. Pregnant rats were fed either 20 or 8% protein isocaloric diets. Control newborns were nursed by their dams fed the 20% protein diet and low protein (LP) pups by dams fed either the 8 or 20% protein diet. The diets given during lactation were maintained until adulthood. The blood vessel density of cerebral cortex analyzed by morphometry in 3-d-old pups from dams fed the 8% protein diet was lower than in control (C). It remained lower at adulthood whether a LP or a C diet was given postnatally. Reduction of vascularization at adulthood induced by the LP diet limited to fetal life seems characteristic for the brain since vascularization of islets of Langerhans was reduced in neonates but normalized at adulthood by a C diet postnatally. Body and brain weights were lower in LP pups and adults. DNA concentration was lower in forebrain and higher in cerebellum in LP pups. In brain of LP adults, DNA, protein, cholesterol and phospholipid concentrations were lower and were restored at adulthood by a normal diet after birth. In conclusion, cerebral cortex of offspring exposed to a LP isocaloric diet during fetal development showed reduced vascularization which remained throughout life.