Perinatal low-protein diet alters brainstem antioxidant metabolism in adult offspring

Background and objectives: Studies in humans and animal models have established a close relationship between early environment insult and subsequent risk of development of non-communicable diseases, including the cardiovascular. Whereas experimental evidences highlight the early undernutrition and the late cardiovascular disease relation, the central mechanisms linking the two remain unknown. Owing to the oxidative balance influence in several pathologies, the aim of the present study was to evaluate the effects of maternal undernutrition (i.e. a low-protein (LP) diet) on oxidative balance in the brainstem.

Methods and results: Male rats from mothers fed with an LP diet (8% casein) throughout the perinatal period (i.e. gestation and lactation) showed 10× higher lipid peroxidation levels than animals treated with normoprotein (17% casein) at 100 days of age. In addition, we observed the following reductions in enzymatic activities: superoxide dismutase, 16%; catalase, 30%; glutathione peroxidase, 34%; glutathione-S-transferase, 51%; glutathione reductase, 23%; glucose-6-phosphate dehydrogenase, 31%; and in non-enzymatic glutathione system, 46%.

Discussion: This study is the first to focus on the role of maternal LP nutrition in oxidative balance in a central nervous system structure responsible for cardiovascular control in adult rats. Our data observed changes in oxidative balance in the offspring, therefore, bring a new concept related to early undernutrition and can help in the development of a new clinical strategy to combat the effects of nutritional insult. Wherein the central oxidative imbalance is a feasible mechanism underlying the hypertension risk in adulthood triggered by maternal LP diet.     

Fetal exposure to a maternal low-protein diet during mid-gestation results in muscle-specific effects on fibre type composition in young rats

This study assessed the impact of reduced dietary protein during specific periods of fetal life upon muscle fibre development in young rats. Pregnant rats were fed a control or low-protein (LP) diet at early (days 0-7 gestation, LPEarly), mid (days 8-14, LPMid), late (days 15-22, LPLate) or throughout gestation (days 0-22, LPAll). The muscle fibre number and composition in soleus and gastrocnemius muscles of the offspring were studied at 4 weeks of age. In the soleus muscle, both the total number and density of fast fibres were reduced in LPMid females (P = 0.004 for both, Diet x Sex x Fibre type interactions), while both the total number and density of glycolytic (non-oxidative) fibres were reduced in LPEarly, LPMid and LPLate (but not LPAll) offspring compared with controls (P < 0.001 for both, Diet x Fibre type interaction). In the gastrocnemius muscle, only the density of oxidative fibres was reduced in LPMid compared with control offspring (P = 0.019, Diet x Fibre type interaction), with the density of slow fibres being increased in LPAll males compared with control (P = 0.024, Diet x Sex x Fibre type interaction). There were little or no effects of maternal diet on fibre type diameters in the two muscles. In conclusion, a maternal low-protein diet mainly during mid-pregnancy reduced muscle fibre number and density in 4-week-old rats, but there were muscle-specific differences in the fibre types affected.     

Short- and long-term effects of a neonatal low-protein diet in rats on the morphology of the larynx

ObjectiveThe aim of this study was to investigate the short- and long-term effects of a maternal low-protein diet during lactation on offspring laryngeal morphology. Our hypothesis was that a neonatal low-protein diet during the critical period of development alters micro- and macroscopic structures of the larynx in adult rats.MethodsMale Wistar rats were assigned to a control (casein 17%, n = 24) or low-protein (casein 8%, n = 24) group according to their mother's diet during lactation. Body weight gain and growth rate were recorded throughout the experiment. The larynx was removed from offspring at days 22 and 60 of life. The anteroposterior and laterolateral lengths of the cartilages epiglottis, thyroid, and cricoid were measured by a digital caliper. The supraglottis, glottis, infraglottis, and vocal cords were stained by hematoxylin–eosin and their structures were analyzed by a Scion Image Beta 4.0.2 program.ResultsPups from mothers fed a low-protein diet showed a lower body weight gain. The laterolateral and anteroposterior lengths of the larynx were shorter in undernourished offspring at 22 d old. There were no differences in the structure of the supraglottis, glottis, and infraglottis between groups except for keratinization in pups from undernourished mothers. The microstructure of the vocal cords was changed only at 60 d old.ConclusionMacroscopic structures of the larynx are sensitive to short-term effects of a neonatal low-protein diet. Vocal cord development can be studied within the context of programming because their microscopic structures are sensitive to the long-term effects of a low-protein diet during lactation.     

Interactions between protein and vegetable oils in the maternal diet determine the programming of the insulin axis in the rat

The available evidence suggests that metabolic control mechanisms are programmed early in life. Previous studies of pregnant rats fed low-protein diets have suggested that the vegetable oils used in the experimental diets influence the outcome. The present study investigated the offspring of female rats fed semi-synthetic diets containing either 180 or 90g casein/kg with 70 g/kg (w/w) of either corn oil or soya oil during gestation. During lactation, the dams received stock diet, and the offspring were subsequently weaned onto the stock diet. The offspring of dams fed the low-protein diets were smaller at birth. At 25 weeks of age, the offspring were subjected to an oral glucose tolerance test. In the offspring of dams fed the diet containing soya oil, the area under the insulin curve was affected by the protein content of the maternal diet. There was no effect of protein on the area under the insulin curve in the offspring of dams fed the diet prepared with corn oil. There were no differences in plasma glucose concentrations. The levels of mRNA for acetyl-CoA carboxylase- in the livers of female offspring were affected by the protein and oil content of the maternal diet. The level of carnitine palmitoyl transferase mRNA was affected by the protein content of the maternal diet. The present study suggests that PUFA in the maternal diet can interact with protein metabolism to influence the development of the offspring. This may involve the higher content of alpha-linolenic acid in soya oil compared with corn oil.     

Soybean diet alters the insulin-signaling pathway in the liver of rats recovering from early-life malnutrition

ObjectiveWe investigated if alterations in the insulin-signaling pathway could contribute to reduced hepatic glycogen levels in adult rats subjected to a protein deficiency during intrauterine life and lactation and reared through to recovery on a soybean diet.MethodsRats from mothers fed with 17% or 6% protein (casein) during pregnancy and lactation were maintained with a 17% casein diet (offspring born to and suckled by mothers fed a control diet and subsequently fed the same diet after weaning [CC group] and offspring born to and suckled by mothers fed a control diet and subsequently fed a soybean flour diet with 17% protein after weaning [CS group]), a soybean diet (offspring of mothers fed a low-protein diet and a control diet after weaning [LC group] and offspring of mothers fed a low-protein diet and fed a soybean flour diet containing 17% protein after weaning [LS group]), or a 6% casein diet (offspring of mothers fed a low-protein diet and subsequently fed the same diet after weaning [LL group]) from weaning until 90 d of life.ResultsA soybean diet did not modify basal serum glucose and glucagon concentrations, but raised basal serum insulin and consequently increased the serum insulin/glucose ratio. Insulin receptor and insulin receptor substrate-1 levels were lower in rats fed a soybean diet compared with those maintained with a casein diet. In the LS group, the p85 levels were higher than in the LC group, whereas in CS rats its expression was lower than in CC rats. The expression of p110 was lower in the CS group compared with the CC group and similar in the LS and LC groups. Insulin receptor substrate-1 phosphorylation was similar in the LS, LC, and CS groups and lower compared with the CC group. The insulin receptor substrate-1–p85/phosphatidylinositol 3-kinase association was lower in LS than in LC rats and in CS than in CC rats. Akt phosphorylation was lower in the CS and LS groups than in the CC and LC groups.ConclusionAdult rats maintained with a soybean diet exhibited insulin resistance due, at least in part, to alterations in the early steps of the insulin signal transduction pathway.     

Maternal protein restriction and fetal growth: lack of evidence of a role for homocysteine in fetal programming

The disease-programming effects of a maternal low-protein (MLP) diet in rat pregnancy have been suggested to be attributable of hyperhomocysteinaemia. The aim of the present study was to determine whether MLP feeding impacted upon maternal and day 20 fetal homocysteine concentrations, with ensuing effects upon oxidant/antioxidant status. Sixty-four pregnant rats were fed either MLP diet or control diet before termination of pregnancy at days 4, 10, 18 or 20 gestation (full-term gestation 22 d). Maternal plasma homocysteine concentrations were similar in control and MLP-fed dams at all points in gestation. Fetal plasma homocysteine was similarly unaffected by MLP feeding at day 20 gestation. Activities of superoxide dismutase and glutathione peroxidase were similar in livers of mothers and fetuses in the two groups. Whilst catalase activity was not influenced by diet in maternal liver, MLP exposure increased catalase activity in fetal liver at day 20. Oxidative injury (protein carbonyl concentration) was lower in the livers of MLP-fed animals at day 18 gestation (P<0.05), but significantly greater at day 20. Hepatic expression of methionine synthase was similar in control and MLP-fed dams at all stages of gestation. Expression of DNA methyltransferase 1 in fetal liver was altered by maternal diet in a sex- and gestational age-specific manner. In conclusion, MLP feeding does not impact upon maternal or fetal homocysteine concentrations prior to day 20 gestation in the rat. There was no evidence of increased oxidative injury in fetal tissue that might explain the long-term programming effects of the diet.     

Maternal low-protein diet-induced delayed reflex ontogeny is attenuated by moderate physical training during gestation in rats

We evaluated the effects of moderate- to low-intensity physical training during gestation on reflex ontogeny in neonate rats whose mothers were undernourished. Virgin female Wistar rats were divided into four groups as follows: untrained (NT, n 7); trained (T, n 7); untrained with a low-protein diet (NT+LP, n 7); trained with a low-protein diet (T+LP, n 4). Trained rats were subjected to a protocol of moderate physical training on a treadmill over a period of 4 weeks (5 d/week and 60 min/d, at 65 % of VO?max). After confirming the pregnancy, the intensity and duration of the exercise were reduced. Low-protein groups were provided with an 8 % casein diet, and controls were provided with a 17 % casein diet. Their respective offspring were evaluated (during the 10th-17th days of postnatal life) in terms of physical feature maturation, somatic growth and reflex ontogeny. Pups born to mothers provided with the low-protein diet during gestation and lactation showed delayed physical feature and reflex maturation and a deficit in somatic growth when compared with controls. However, most of these deficiencies were attenuated in pups of undernourished mothers undergoing training. In conclusion, physical training during gestation attenuates the effects of perinatal undernutrition on some patterns of maturation in the central nervous system during development.     

Maternal High-Fiber Diet Protects Offspring against Type 2 Diabetes

Previous studies have reported that maternal malnutrition is linked to increased risk of developing type 2 diabetes in adulthood. Although several diabetic risk factors associated with early-life environment have been identified, protective factors remain elusive. Here, we conducted a longitudinal study with 671 Nile rats whereby we examined the interplay between early-life environment (maternal diet) and later-life environment (offspring diet) using opposing diets that induce or prevent diet-induced diabetes. Specifically, we modulated the early-life environment throughout oogenesis, pregnancy, and nursing by feeding Nile rat dams a lifelong high-fiber diet to investigate whether the offspring are protected from type 2 diabetes. We found that exposure to a high-fiber maternal diet prior to weaning significantly lowered the risk of diet-induced diabetes in the offspring. Interestingly, offspring consuming a high-fiber diet after weaning did not develop diet-induced diabetes, even when exposed to a diabetogenic maternal diet. Here, we provide the first evidence that the protective effect of a high-fiber diet can be transmitted to the offspring through the maternal diet, which has important implications in diabetes prevention.     

Maternal One-Carbon Supplement Reduced the Risk of Non-Alcoholic Fatty Liver Disease in Male Offspring

Recent studies have suggested that prevention of obesity and non-alcoholic fatty liver disease (NAFLD) should start with maternal dietary management. We previously reported disrupted methionine cycle, associated with NAFLD, in male offspring liver due to maternal high-fat (HF) diet, thus we hypothesize that maternal one-carbon supplement may reduce the risk of NAFLD in offspring via the normalizing methionine cycle. To test it, female mice (F0) were exposed to either a maternal normal-fat diet (NF group) a maternal HF diet (HF group), or a maternal methyl donor supplement (H1S or H2S group) during gestation and lactation. The offspring male mice (F1) were exposed to a postweaning HF diet to promote NAFLD. While the HF offspring displayed obesity, glucose intolerance and hepatic steatosis, the H1S and H2S offspring avoided hepatic steatosis. This phenotype was associated with the normalization of the methionine cycle and the restoration of L-carnitine and AMPK activity. Furthermore, maternal HF diet induced epigenetic regulation of important genes involved in fatty acid oxidation and oxidative phosphorylation via DNA methylation modifications, which were recovered by maternal one-carbon supplementation. Our study provides evidence that maternal one-carbon supplement can reverse/block the adverse effects of maternal HF diet on promoting offspring NAFLD, suggesting a potential nutritional strategy that is administered to mothers to prevent NAFLD in the offspring.     

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.     

The influence of maternal diet on breast cancer risk among female offspring.

The induction of breast cancer is a long process, containing a series of biological events that drive a normal mammary cell towards malignant growth. However, it is not known when the initiation of breast cancer occurs. One hypothesis is that a high estrogenic environment during the perinatal period increases subsequent breast cancer risk. There are many sources of extragonadal estrogens, particularly in the diet. The purpose of this paper is to review the evidence that a high maternal intake of dietary fats increases serum estrogens during pregnancy and increases breast cancer risk in daughters. Our animal studies show that a high maternal consumption of corn oil consisting mainly of linoleic acid (omega-6 polyunsaturated fatty acid, PUFA), increases both circulating estradiol (E2) levels during pregnancy and the risk of developing carcinogen-induced mammary tumors among the female rat offspring. A similar increase in breast cancer risk occurs in female offspring exposed to injections of E2 through their pregnant mother. Our data suggest that the mechanisms by which an early exposure to dietary fat and/or estrogens increases breast cancer risk is related to reduced differentiation of the mammary epithelial tree and increased number of mammary epithelial cell structures that are known to the sites of neoplastic transformation. These findings may reflect our data of the reduced estrogen receptor protein levels and protein kinase C activity in the developing mammary glands of female rats exposed to a high-fat diet in utero. In summary, a high dietary linoleic acid intake can elevate pregnancy estrogen levels and this, possibly by altering mammary gland morphology and expression of fat- and/or estrogen-regulated genes, can increase breast cancer risk in the offspring. If true for women, breast cancer prevention in daughters may include modulating the mother's pregnancy intake of some dietary fats.     

Azuki bean polyphenols intake during lactation upregulate AMPK in male rat offspring exposed to fetal malnutrition

ObjectiveFetal malnutrition is an early-life inducer of dyslipidemia and glucose intolerance. The aim of this study was to examine whether maternal azuki bean (Vigna angularis) polyphenol (AP) intake during lactation affects the adenosine monophosphate–activated protein kinase (AMPK) pathway and lipid metabolism in offspring exposed to fetal malnutrition.MethodsPregnant Wistar rats were divided into three groups: a control diet offered during gestation and lactation (CC), a low-protein diet during gestation and a control diet during lactation (LPC); and a low-protein diet during gestation and a 1.0% AP-containing control diet during lactation (LPAP). Male pups were randomly selected for the study; half the pups were sacrificed at 3 wk of age and the other half were fed a standard diet and sacrificed at 23 wk. Hepatic triacylglycerol levels, phosphorylation levels of AMPK and acetyl-coenzyme A carboxylase (ACC), and mRNA levels of sterol regulatory element-binding protein-1c (SREBP-1c) were evaluated.ResultsSignificant decreases in body weights and hepatic triacylglycerol levels were found in the LPAP compared with the LPC group. Plasma adiponectin levels in the LPAP group were higher than those in the LPC group. AMPK phosphorylation was upregulated in the livers and skeletal muscles in young and adult LPAP compared with LPC rats. ACC phosphorylation was upregulated in skeletal muscles of LPAP rats. SREBP-1c mRNA expression was decreased in the livers of LPAP rats.ConclusionOur results suggest that maternal AP intake during lactation upregulates AMPK phosphorylation not only in young but also in adult offspring exposed to fetal malnutrition and may lead to decreased hepatic lipid accumulation by ACC phosphorylation and downregulation of SREBP-1c expression.     

Maternal Fructose Intake Exacerbates Cardiac Remodeling in Offspring with Ventricular Pressure Overload

Recent studies demonstrated that metabolic syndrome and cardiovascular diseases could be elicited by developmental programming, which is regulated by prenatal nutritional and environmental stress. In this study, we utilized a rat model to examine the effect of excessive maternal fructose intake during pregnancy and lactation on cardiac development and progression of pressure overload-induced cardiac hypertrophy in offspring. Transverse aortic constriction (TAC) was performed on 3-month-old male offspring to induce ventricular pressure overload. Four weeks post-TAC, echocardiographic assessment as well as histopathological and biochemical examinations were performed on the myocardium of the offspring. Echocardiographic and gross examinations showed that heart weight, interventricular septal thickness in diastole (IVD; d), and left ventricular posterior wall thickness in diastole (LVPW; d) were elevated in offspring with TAC and further increased by maternal fructose exposure (MFE). However, the left ventricular ejection function was not significantly affected. Myocardial histopathological examination revealed that the indices of fibrosis and oxidative stress were higher in offspring with MFE and TAC than those in animals receiving either treatment. Molecular examinations on the myocardium demonstrated an MFE-induced upregulation of p38-MAPK signaling. Next generation sequence (NGS) analysis indicated a modulation of the expression levels of several cardiac hypertrophy-associated genes, including GPR22, Myh7, Nppa, P2RX4, and Npy by MFE. Subsequent RT-PCR indicated that MFE regulated the expression levels of genes responsive to cardiac hypertrophy (i.e., Myh-7, ANP) and oxidative stress (i.e., GR, GPx, and NQO-1). In conclusion, MFE during pregnancy and lactation modulated myocardial gene expression, increased oxidative stress, and exacerbated ventricular pressure overload-induced cardiac remodeling in rat offspring.     

Mortality of mothers from cardiovascular and non‐cardiovascular causes following pregnancy complications in first delivery

Lykke JA, Langhoff‐Roos J, Lockwood CJ, Triche EW, Paidas MJ. Mortality of mothers from cardiovascular and non‐cardiovascular causes following pregnancy complications in first delivery. Paediatric and Perinatal Epidemiology 2010. The combined effects of preterm delivery, small‐for‐gestational‐age offspring, hypertensive disorders of pregnancy, placental abruption and stillbirth on early maternal death from cardiovascular causes have not previously been described in a large cohort. We investigated the effects of pregnancy complications on early maternal death in a registry‐based retrospective cohort study of 782 287 women with a first singleton delivery in Denmark 1978–2007, followed for a median of 14.8 years (range 0.25–30.2) accruing 11.6 million person‐years. We employed Cox proportional hazard models of early death from cardiovascular and non‐cardiovascular causes following preterm delivery, small‐for‐gestational‐age offspring and hypertensive disorders of pregnancy. We found that preterm delivery and small‐for‐gestational‐age were both associated with subsequent death of mothers from cardiovascular and non‐cardiovascular causes. Severe pre‐eclampsia was associated with death from cardiovascular causes only. There was a less than additive effect on cardiovascular mortality hazard ratios with increasing number of pregnancy complications: preterm delivery 1.90 [95% confidence intervals 1.49, 2.43]; preterm delivery and small‐for‐gestational‐age offspring 3.30 [2.25, 4.84]; preterm delivery, small‐for‐gestational‐age offspring and pre‐eclampsia 3.85 [2.07, 7.19]. Thus, we conclude that, separately and combined, preterm delivery and small‐for‐gestational‐age are strong markers of early maternal death from both cardiovascular and non‐cardiovascular causes, while hypertensive disorders of pregnancy are markers of early death of mothers from cardiovascular causes.     

High Dietary Fat Intake during Lactation Promotes the Development of Social Stress-Induced Obesity in the Offspring of Mice

This study examined how a maternal high-fat diet (HD) during lactation and exposure of offspring to isolation stress influence the susceptibility of offspring to the development of obesity. C57BL/6J mice were fed a commercial diet (CD) during pregnancy and a CD or HD during lactation. Male offspring were weaned at three weeks of age, fed a CD until seven weeks of age, and fed a CD or HD until 11 weeks of age. Offspring were housed alone (isolation stress) or at six per cage (ordinary circumstances). Thus, offspring were assigned to one of eight groups: dams fed a CD or HD during lactation and offspring fed a CD or HD and housed under ordinary circumstances or isolation stress. Serum corticosterone level was significantly elevated by isolation stress. High-fat feeding of offspring reduced their serum corticosterone level, which was significantly elevated by a maternal HD. A maternal HD and isolation stress had combined effects in elevating the serum corticosterone level. These findings suggest that a maternal HD during lactation enhances the stress sensitivity of offspring. White adipose tissue weights were significantly increased by a maternal HD and isolation stress and by their combination. In addition, significant adipocyte hypertrophy was induced by a maternal HD and isolation stress and exacerbated by their combination. Thus, a maternal HD and isolation stress promote visceral fat accumulation and adipocyte hypertrophy, accelerating the progression of obesity through their combined effects. The mechanism may involve enhanced fatty acid synthesis and lipid influx from blood into adipose tissue. These findings demonstrate that a maternal HD during lactation may increase the susceptibility of offspring to the development of stress-induced obesity.     

Diet and Maternal Obesity Are Associated with Increased Oxidative Stress in Newborns: A Cross-Sectional Study

Overweight and obesity have become a world-health public problem, mainly for developing countries. Both health conditions have a higher prevalence among women of childbearing age. Physiopathology, overweight and obesity are characterized by a chronic oxidative stress status, which has deleterious effects on mothers and children. Hence, we determine whether the qualities of diet during pregnancy and maternal pregestational body mass index (BMI) are associated with increased oxidative stress markers in mothers and newborns. Two hundred forty-two (242) mother-newborn pairs were classified according to their pregestational BMI. Information on food intake was collected using a food frequency questionnaire in the third trimester of pregnancy. Levels of Malondialdehyde (MDA) and Nitric Oxide (NO) were measured in plasma from mothers at the end of the third trimester of pregnancy and from cord blood at birth. MDA and NO levels in mother–newborn pairs with maternal pregestational overweight or obesity were higher than in mother–newborn pairs with pregestational normal weight. For women (and newborns) who had a higher intake of fruit and vegetables, the levels of NO and MDA were lower. Lastly, women with pregestational obesity had lower fruit and vegetable intake during pregnancy and higher levels of oxidative stress and in their newborns.     

Long-term programming of blood pressure by maternal dietary iron restriction in the rat

We have reported that blood pressure was elevated in 3-month-old rats whose mothers were Fe-restricted during pregnancy. These animals also had improved glucose tolerance and decreased serum triacylglycerol. The aim of the present study was to determine whether these effects of maternal nutritional restriction, present in these animals at 3 months of age, can be observed in the same animals in later life. Pulmonary and serum angiotensin converting enzyme (ACE) concentrations were also measured to investigate whether the renin-angiotensin system was involved in the elevation of blood pressure observed in the offspring of Fe-restricted dams. Systolic blood pressure was higher in the offspring of Fe-restricted dams at 16 months of age. Heart and kidney weight were increased as a proportion of body weight in the offspring of Fe-restricted dams. The pulmonary ACE concentration was not significantly different between the groups. The serum ACE concentration was significantly elevated in the offspring of Fe-restricted dams at 3 but not 14 months of age. There was a strong correlation between serum ACE levels at 3 and 14 months of age. Glucose tolerance and serum insulin were not different between the maternal diet groups. Serum triacylglycerol tended to be lower in the offspring of Fe-restricted dams. There were no differences in serum non-esterified fatty acids or serum cholesterol between the maternal diet groups. This study provides further evidence that maternal nutrition has effects on the offspring that persist throughout life. At 16 months of age, the elevation of blood pressure in Fe-restricted offspring does not appear to be mediated via changes in ACE levels. Both cardiac hypertrophy and decreased serum triacylglycerol have also been observed in Fe-restricted fetuses, suggesting that these changes may be initiated in utero.     

The effects of maternal protein restriction on the growth of the rat fetus and its amino acid supply.

Maternal protein deficiency causes fetal growth retardation which has been associated with the programming of adult disease. The growth of the rat fetus was examined when the mothers were fed on diets containing 180, 90 and 60 g protein/kg. The numbers of fetuses were similar in animals fed on the 180 and 90 g protein/kg diets but the number was significantly reduced in the animals fed on the 60 g protein/kg diet. The fetuses carried by the mothers fed on the 90 g protein/kg diet were 7.5% heavier than those of mothers fed on 180 g protein/kg diet on day 19 of gestation, but by day 21 the situation was reversed and the fetuses in the protein-deficient mothers were 14% smaller. Analysis of the free amino acids in the maternal serum showed that on day 19 the diets containing 90 and 60 g protein/kg led to threonine concentrations that were reduced to 46 and 20% of those found in animals fed on the control (180 g/kg) diet. The other essential amino acids were unchanged, except for a small decrease in the branched-chain amino acids in animals fed on the 60 g protein/kg diet. Both low-protein diets significantly increased the concentrations of glutamic acid+glutamine and glycine in the maternal serum. On day 21 the maternal serum threonine levels were still reduced by about one third in the group fed on the 90 g protein/kg diet. Dietary protein content had no effect on serum threonine concentrations in nonpregnant animals. Analysis of the total free amino acids in the fetuses on day 19 showed that feeding the mother on a low-protein diet did not change amino acid concentrations apart from a decrease in threonine concentrations to 45 and 26% of the control values at 90 and 60 g protein/ kg respectively. The results suggest that threonine is of particular importance to the protein-deficient mother and her fetuses. Possible mechanisms for the decrease in free threonine in both mother and fetuses and the consequences of the change in amino acid metabolism are discussed.     

A maternal 'junk food' diet in pregnancy and lactation promotes an exacerbated taste for 'junk food' and a greater propensity for obesity in rat offspring

Obesity is generally associated with high intake of junk foods rich in energy, fat, sugar and salt combined with a dysfunctional control of appetite and lack of exercise. There is some evidence to suggest that appetite and body mass can be influenced by maternal food intake during the fetal and suckling life of an individual. However, the influence of a maternal junk food diet during pregnancy and lactation on the feeding behaviour and weight gain of the offspring remains largely uncharacterised. In this study, six groups of rats were fed either rodent chow alone or with a junk food diet during gestation, lactation and/or post-weaning. The daily food intakes and body mass were measured in forty-two pregnant and lactating mothers as well as in 216 offspring from weaning up to 10 weeks of age. Results showed that 10 week-old rats born to mothers fed the junk food diet during gestation and lactation developed an exacerbated preference for fatty, sugary and salty foods at the expense of protein-rich foods when compared with offspring fed a balanced chow diet prior to weaning or during lactation alone. Male and female offspring exposed to the junk food diet throughout the study also exhibited increased body weight and BMI compared with all other offspring. This study shows that a maternal junk food diet during pregnancy and lactation may be an important contributing factor in the development of obesity.