Postnatal Diet Research Articles

Evidence for the essentiality of arachidonic and docosahexaenoic acid in the postnatal maternal and infant diet for the development of the infant's immune system early in life.

Long-chain polyunsaturated fatty acids (LCPUFA), especially the balance between arachidonic (AA) and docosahexaenoic (DHA) acids are known to have important immunomodulatory roles during the postnatal period when the immune system is rapidly developing. AA and DHA are required in infant formula in many countries but are optional in North America. The rationale for adding these LCPUFA to full-term formula is based on their presence in breast milk and randomized controlled studies that suggest improved cognitive function in preterm infants, but results are more variable in full-term infants. Recently, the European Food Safety Authority has proposed, based on a lack of functional evidence, that AA is not required in infant formula for full-term infants during the first year of life but DHA should remain mandatory. The purpose of this review is to review the evidence from epidemiological and intervention studies regarding the essentiality of AA and DHA in the postnatal infant and maternal diet (breast-feeding) for the immune system development early in life. Although studies support the essentiality of DHA for the immune system development, more research is needed to rule out the essentiality of AA. Nevertheless, intervention studies have demonstrated improvement in many markers of immune function in infants fed formula supplemented with AA and DHA compared with unsupplemented formula, which appears to consistently result in beneficial health outcomes including reduction in the risk of developing allergic and atopic disease early in life.

Maternal N-acetylcysteine therapy regulates hydrogen sulfide-generating pathway and prevents programmed hypertension in male offspring exposed to prenatal dexamethasone and postnatal high-fat diet

Nitric oxide (NO) and hydrogen sulfide (H2S) pathways are involved in the development of hypertension, a condition that can originate from early life. We examined whether asymmetric dimethylarginine (ADMA, a nitric oxide synthase inhibitor)/NO and H2S generating pathway contributed to programmed hypertension in offspring exposed to prenatal dexamethasone (DEX) and postnatal high-fat (HF) and whether N-acetylcysteine (NAC) therapy prevented this process. We examined 16-week-old male rat offspring from five groups: control, DEX (0.1 mg/kg i.p. from gestational day 16–22), HF (58% high-fat diet from weaning to 4 months of age), DEX+HF, and NAC (1% in drinking water during lactation). Prenatal DEX and postnatal HF diet synergistically induced programmed hypertension in adult offspring, which was prevented by maternal NAC therapy. We attributed the protective effects of NAC on two-hit induced programmed hypertension to the reduction of plasma ADMA, restoration of plasma l-arginine-to-ADMA ratio, upregulation of gene expression of H2S-generating enzymes, restoration of renal 3-mercaptopyruvate sulphurtransferase (3MST) protein levels and activity, induction of plasma glutathione level, and reduction of oxidative stress. Manipulation of the ADMA-NO and H2S-generating pathways by maternal NAC therapy may be a potential approach to prevent programmed hypertension induced by two-hit insults.

Maternal dietary fat intake during pregnancy is associated with infant temperament.

Research with rodents and nonhuman primates suggests that maternal prenatal dietary fat intake is associated with offspring behavioral functioning indicative of risk for psychopathology. The extent to which these findings extend to humans remains unknown. The current study administered the Automated Self-Administered 24 hr Dietary Recall Questionnaire three times in pregnancy (n = 48) to examine women's dietary fat intake in relation to infant temperament assessed using the Infant Behavior Questionnaire at 4-months old. The amount of saturated fat that the mother consumed was considered as a moderator of the association between total fat intake and child temperament. Results from a series of multiple linear regressions indicate that greater total fat intake was associated with poorer infant regulation and lower surgency. However, this second effect was moderated by maternal saturated fat intake, such that total fat intake was only related to infant surgency when mothers consumed above the daily recommended allowance of saturated fat. Under conditions of high total fat and high saturated fat, infants were rated as lower on surgency; under conditions of low total fat yet high saturated fat, infants were rated as higher on surgency. There were no associations between maternal prenatal fat intake and infant negative reactivity. These findings provide preliminary evidence that pregnant women's dietary fat intake is associated with infants' behavioral development, though future research is needed to address this report's limitations: a relatively small sample size, the use of self-report measures, and a lack of consideration of maternal and infant postnatal diet.

Postnatal high-fat diet enhances ectopic fat deposition in pigs with intrauterine growth retardation.

Intrauterine growth retardation (IUGR) and postnatal nutrition are risk factors for adult metabolic syndrome. However, the influences of long-term high-fat diet (HFD) intake on ectopic fat deposition in non-adipose tissues in IUGR pigs remain unclear. The present study was to determine whether HFD consumption would enhance ectopic fat deposition in IUGR pigs. At day 28, IUGR and control pigs were fed ad libitum to either a regular diet or a HFD. Lipid store, enzymatic activities and mRNA expression of lipid metabolism-related factors in liver and semitendinosus muscle (SM) were quantified at postnatal day 178. Feeding a HFD to IUGR pigs but not to control pigs significantly increased daily weight gain, carcass fat mass, plasma leptin level and lipid content and lipoprotein lipase (LPL) activity and mRNA abundances of LPL and peroxisome proliferator-activated receptor gamma (PPARγ) in liver and SM, but decreased daily feed intake and mRNA expression of hormone-sensitive lipase (LIPE) and carnitine palmitoyl transferase-1 (CPT-1) in liver and SM (P<0.05). Compared with control pigs, IUGR pigs had a lower body weight but higher plasma levels of total cholesterol (TC) and insulin (P<0.05). HFD-fed pigs exhibited greater body weight, plasma concentrations of triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), regardless of birth weight (P<0.05). Our results suggested that IUGR increased the vulnerability of HFD-fed pigs to ectopic fat deposition via enhanced fatty acid flux toward ectopic sites and reduced lipolysis and fatty acid oxidation.

Maternal obesity and malnourishment exacerbate perinatal oxidative stress resulting in diabetogenic programming in F1 offspring.

The effect of in-utero environment on fetal health and survival is long-lasting, and this is known as the fetal origin hypothesis. The oxidative stress state during gestation could play a pivotal role in fetal programming and development of diseases such as diabetes. In this study, we investigated the effect of intra-uterine obesity and malnutrition on oxidative stress markers in pancreatic and peripheral tissues of F1 offspring both prenatally and postnatally. Furthermore, the effect of postnatal diet on oxidative stress profile was evaluated. The results indicated that intra-uterine obesity and malnourishment significantly increased oxidative stress in F1 offspring. Moreover, the programming effect of obesity was more pronounced and protracted than malnutrition. The obesity-induced programming of offspring tissues was independent of high-caloric environment that the offspring endured; however, high-caloric diet potentiated its effect. In addition, pancreas and liver were the most affected tissues by fetal reprogramming both prenatally and postnatally. In conclusion, maternal obesity and malnutrition-induced oxidative stress could predispose offspring to insulin resistance and diabetes.

Maternal Melatonin Therapy Rescues Prenatal Dexamethasone and Postnatal High-Fat Diet Induced Programmed Hypertension in Male Rat Offspring.

Prenatal dexamethasone (DEX) exposure and high-fat (HF) intake are linked to hypertension. We examined whether maternal melatonin therapy prevents programmed hypertension synergistically induced by prenatal DEX plus postnatal HF in adult offspring. We also examined whether DEX and melatonin causes renal programming using next-generation RNA sequencing (NGS) technology. Pregnant Sprague-Dawley rats received intraperitoneal dexamethasone (0.1 mg/kg) or vehicle from gestational day 16 to 22. In the melatonin-treatment groups (M), rats received 0.01% melatonin in drinking water during their entire pregnancy and lactation. Male offspring were assigned to five groups: control, DEX, HF, DEX+HF, and DEX+HF+M. Male offspring in the HF group were fed a HF diet from weaning to 4 months of age. Prenatal DEX and postnatal HF diet synergistically induced programmed hypertension in adult offspring, which melatonin prevented. Maternal melatonin treatment modified over 3000 renal transcripts in the developing offspring kidney. Our NGS data indicate that PPAR signaling and fatty acid metabolism are two significantly regulated pathways. In addition, maternal melatonin therapy elicits longstanding alterations on renal programming, including regulation of the melatonin signaling pathway and upregulation of Agtr1b and Mas1 expression in the renin-angiotensin system (RAS), to protect male offspring against programmed hypertension. Postnatal HF aggravates prenatal DEX induced programmed hypertension in adult offspring, which melatonin prevented. The protective effects of melatonin on programmed hypertension is associated with regulation of the RAS and melatonin receptors. The long-term effects of maternal melatonin therapy on renal transcriptome require further clarification.

Effect of resveratrol on metabolic and cardiovascular function in male and female adult offspring exposed to prenatal hypoxia and a high-fat diet.

Prenatal hypoxia, a common outcome of pregnancy complications, predisposes offspring to the development of metabolic and cardiovascular disorders in later life. We have previously observed that resveratrol improved cardiovascular and metabolic health in adult male rat offspring exposed to prenatal hypoxia and a postnatal high-fat (HF) diet; however, the effects of resveratrol in female rat offspring are not known. Our aim was to identify the mechanism(s) by which resveratrol may prevent metabolic and cardiac dysfunction in both male and female rat offspring exposed to prenatal hypoxia and a postnatal HF diet. Offspring that experienced normoxia or hypoxia in utero were fed a HF diet or a HF diet supplemented with resveratrol for 9 weeks following weaning. Body composition, metabolic function, in vivo cardiac function and ex vivo cardiac susceptibility to ischaemia-reperfusion (I/R) injury were assessed at 12 weeks of age. Prenatal hypoxia impaired metabolic function in male, but not female, rat offspring fed a HF diet and this was improved by resveratrol supplementation. Prenatal hypoxia also led to reduced recovery from cardiac I/R injury in male, and to a lesser extent in female, rat offspring fed a HF diet. Indices of cardiac oxidative stress after I/R were enhanced in both male and female rat offspring exposed to prenatal hypoxia. Resveratrol improved cardiac recovery from I/R injury and attenuated superoxide levels in both male and female rat offspring. In conclusion, prenatal hypoxia impaired metabolic and cardiac function in a sex-specific manner. Resveratrol supplementation may improve metabolic and cardiovascular health in adult male and female rat offspring exposed to prenatal hypoxia.

Late gestational hypoxia and a postnatal high salt diet programs endothelial dysfunction and arterial stiffness in adult mouse offspring.

Gestational hypoxia and high dietary salt intake have both been associated with impaired vascular function in adulthood. Using a mouse model of prenatal hypoxia, we examined whether a chronic high salt diet had an additive effect in promoting vascular dysfunction in offspring. Pregnant CD1 dams were placed in a hypoxic chamber (12% O2) or housed under normal conditions (21% O2) from embryonic day 14.5 until birth. Gestational hypoxia resulted in a reduced body weight for both male and female offspring at birth. This restriction in body weight persisted until weaning, after which the animals underwent catch-up growth. At 10 weeks of age, a subset of offspring was placed on a high salt diet (5% NaCl). Pressurized myography of mesenteric resistance arteries at 12 months of age showed that both male and female offspring exposed to maternal hypoxia had significantly impaired endothelial function, as demonstrated by impaired vasodilatation to ACh but not sodium nitroprusside. Endothelial dysfunction caused by prenatal hypoxia was not exacerbated by postnatal consumption of a high salt diet. Prenatal hypoxia increased microvascular stiffness in male offspring. The combination of prenatal hypoxia and a postnatal high salt diet caused a leftward shift in the stress-strain relationship in both sexes. Histopathological analysis of aortic sections revealed a loss of elastin integrity and increased collagen, consistent with increased vascular stiffness. These results demonstrate that prenatal hypoxia programs endothelial dysfunction in both sexes. A chronic high salt diet in postnatal life had an additive deleterious effect on vascular mechanics and structural characteristics in both sexes.

Association between intrauterine mild hyperglycemia and post-natal high-fat diet with adiponectin and AMPK pathway genes

To investigate the mechanisms of maternal–fetal interactions in the setting of gestational diabetes mellitus. We investigated the long-term effects of intrauterine mild hyperglycemia and a postnatal high-fat diet on the glucose metabolism of adult offspring, and explored the role of adiponectin on hepatic gluconeogenesis. Twenty-one pregnant Wistar rats were randomly divided into an intrauterine hyperglycemia group (group D, n = 14) and a control group (group C, n = 7). Offspring were divided into four groups according to intrauterine blood glucose level and post-weaning dietary patterns (high-fat diet groups: DF and CF or normal diet groups: DN and CN, n = 8 per group). The average birth weights of group D offspring were higher than for group C. In the DF rats, low adiponectin mRNA expression in perirenal and epididymal fat was significantly positively correlated with low hepatic AdipoR1 mRNA expression and significantly correlated with high hepatic PEPCK, G-6-Pase, and PGC-1α mRNA levels. In DF rats, hepatic P-AMPK was cytoplasmically located and its level was decreased; in these rats, hepatic CRTC2 was expressed in the nucleus and its level was significantly increased. Our study shows that the dietary structure of offspring has a large influence on the incidence of abnormal glucose tolerance.

Reversing Fetal Undernutrition by Kick-Starting Early Growth.

The relationship between poor maternal nutritional status and enhanced chronic disease risk in the offspring is now abundantly established in both experimental models and in epidemiological data from human populations worldwide. The classic studies of Barker et al (1), demonstrating a relationship between low birth weight (LBW) and increased risk of cardiovascular disease, hypertension, and dyslipidemia, paved the way for extensive research into the influence of the intrauterine environment on development of chronic diseases. In these original studies, men in their sixties who were smallest at birth had a 3-fold higher death rate from ischemic heart failure compared with those with high birth weights (1). Likewise, incidence of type 2 diabetes and glucose intolerance was also significantly higher in men with LBWs (2). To add to an expanding list of ailments, it is now well accepted that the propensity to develop obesity, type 2 diabetes, immunologic dysfunction, insulin resistance and related metabolic diseases is, in part, influenced by the maternal in utero environment (3). The focus of many investigations on LBW and conditions that lead to small babies arises from the fact that environmental factors and nutrient supply play an important role in determining birth weight and alterations in birth weight represent a gross deviation in the fetal experience. Nonetheless, changes in birth weight should not be confused to be a sine quo non in developmental programming, because it is quite evident that longterm alterations in risk occur well below the threshold of alterations in body weight at birth. Over the last decade and half, an explosion of studies using a variety of approaches has shown that developmental programming occurs in the contexts of both maternal undernutrition and overnutrition (3). Although one’s genetic makeup, postnatal diet, and lifestyle factors such as physical activity indisputably are important proximate causes of obesity, the influence of gestational experiences is evident in the Uor J-shaped relationship between birth weight and later obesity risk, suggesting that both extremes of nutritional environments lead to detrimental changes in the offspring. Certainly, this is relevant to the current global epidemic of obesity and ubiquitous consumption of calorically dense diets, high in fat and simple sugars both before and during pregnancy (4, 5). The conceptual framework provided by the developmental origins of health and disease hypothesis posits that unfavorable prenatal and postnatal environments, specifically during sensitive periods in development, lead to permanent alterations in organ structure and function that may confer increased risk towards a variety of chronic diseases (6). As elaborated in the predictive adaptive response hypothesis (7, 8), these adaptive changes, facilitated by the process of developmental plasticity are designed to be beneficial in ensuring short-term survival and preparing for a “predicted” postnatal environment. However, when presented with a highly discrepant postnatal environment, mismatch ensues and these changes may prove disadvantageous or maladaptive, thereby increasing predisposition to disease. Evidence from follow up of individuals affected during the Dutch Hunger Winter famine during the latter part of the Second World War and the Chinese famine (1959–1961) lend strong support to this hypothesis (9, 10). Furthermore, high rates of obesity and diabetes in populations where poor maternal nutrition is historically prevalent in combination with current trends of urbanization, as evidenced in many developing nations, also presents an ongoing natural experiment. Despite

Reduced linoleic acid intake in early postnatal life improves metabolic outcomes in adult rodents following a Western-style diet challenge

The global increase in dietary n-6 polyunsaturated fatty acid (PUFA) intake has been suggested to contribute to the rise in obesity incidence. We hypothesized that reduced n-6 PUFA intake during early postnatal life improves adult body composition and metabolic phenotype upon a Western diet challenge. Male offspring of C57Bl/6j mice and Wistar rats were subjected to a control diet (CTRL; 3.16 En% linoleic acid [LA]) or a low n-6 PUFA diet (low LA; 1.36 En% LA) from postnatal days (PNs) 2 to 42. Subsequently, all animals were switched to a Western-style diet (2.54 En% LA) until PN98. We monitored body composition by dual-energy x-ray absorptiometry and glucose homeostasis by an intravenous glucose and insulin tolerance test in rats and by the homeostasis model assessment of insulin resistance (HOMA-IR) in mice. At PN98, plasma lipids, glucose, insulin, and adipokines were measured and adipocyte number and size were analyzed. In mice, the postnatal low-LA diet decreased fat accumulation during the adult Western-style diet challenge (−27% compared with CTRL, P < .001). Simultaneously, it reduced fasting triglyceride levels and lowered fasting resistin and leptin levels. In rats, the low-LA diet did not affect adult body composition, but decreased the number of retroperitoneal adipocytes and increased the number of large adipocytes. In conclusion, lowering dietary n-6 PUFA intake in early life protected against detrimental effects of an obesogenic diet in adulthood on metabolic homeostasis and fat mass accumulation.

Maternal obesity characterized by gestational diabetes increases the susceptibility of rat offspring to hepatic steatosis via a disrupted liver metabolome.

Maternal obesity is associated with a high risk for gestational diabetes mellitus (GDM), which is a common complication of pregnancy. The influence of maternal obesity and GDM on the metabolic health of the offspring is poorly understood. We hypothesize that GDM associated with maternal obesity will cause obesity, insulin resistance and hepatic steatosis in the offspring. Female Sprague-Dawley rats were fed a high-fat (45%) and sucrose (HFS) diet to cause maternal obesity and GDM. Lean control pregnant rats received low-fat (LF; 10%) diets. To investigate the interaction between the prenatal environment and postnatal diets, rat offspring were assigned to LF or HFS diets for 12 weeks, and insulin sensitivity and hepatic steatosis were evaluated. Pregnant GDM dams exhibited excessive gestational weight gain, hyperinsulinaemia and hyperglycaemia. Offspring of GDM dams gained more weight than the offspring of lean dams due to excess adiposity. The offspring of GDM dams also developed hepatic steatosis and insulin resistance. The postnatal consumption of a LF diet did not protect offspring of GDM dams against these metabolic disorders. Analysis of the hepatic metabolome revealed increased diacylglycerol and reduced phosphatidylethanolamine in the offspring of GDM dams compared to offspring of lean dams. Consistent with altered lipid metabolism, the expression of CTP:phosphoethanolamine cytidylyltransferase, and peroxisomal proliferator activated receptor-α mRNA was reduced in the livers of GDM offspring. GDM exposure programs gene expression and hepatic metabolite levels and drives the development of hepatic steatosis and insulin resistance in young adult rat offspring.

Epigenetic and developmental influences on the risk of obesity, diabetes, and metabolic syndrome.

Metabolic syndrome is a growing cause of morbidity and mortality worldwide. Metabolic syndrome is characterized by the presence of a variety of metabolic disturbances including obesity, hyperlipidemia, hypertension, and elevated fasting blood sugar. Although the risk for metabolic syndrome has largely been attributed to adult lifestyle factors such as poor nutrition, lack of exercise, and smoking, there is now strong evidence suggesting that predisposition to the development of metabolic syndrome begins in utero. First posited by Hales and Barker in 1992, the “thrifty phenotype” hypothesis proposes that susceptibility to adult chronic diseases can occur in response to exposures in the prenatal and perinatal periods. This hypothesis has been continually supported by epidemiologic studies and studies involving animal models. In this review, we describe the structural, metabolic and epigenetic changes that occur in response to adverse intrauterine environments including prenatal and postnatal diet, maternal obesity, and pregnancy complications. Given the increasing prevalence of metabolic syndrome in both the developed and developing worlds, a greater understanding and appreciation for the role of the intrauterine environment in adult chronic disease etiology is imperative.

Maternal high-protein diet during pregnancy, but not during suckling, induced altered expression of an increasing number of hepatic genes in adult mouse offspring.

Indirect effects of a high-protein maternal diet are not well understood. In this study, we analyzed short-term and sustainable effects of a prenatal versus early postnatal maternal high-protein diet on growth and hepatic gene expression in mouse offspring. Dams were exposed to an isoenergetic high-protein (HP, 40 % w/w) diet during pregnancy or lactation. Growth and hepatic expression profiles of male offspring were evaluated directly after weaning and 150 days after birth. Offspring from two dietary groups, high-protein diet during pregnancy and control diet during lactation (HPC), and control diet during pregnancy and high-protein diet during lactation (CHP), were compared with offspring (CC) from control-fed dams. Maternal CHP treatment was associated with sustained offspring growth retardation, but decreased numbers of affected hepatic genes in adults compared to weanlings. In contrast, offspring of the HPC group did not show persistent effects on growth parameters, but the number of affected hepatic genes was even increased at adult age. In both dietary groups, however, only a small subset of genes was affected in weanlings as well as in adults. We conclude that (1) prenatal and early postnatal maternal HP diet caused persistent, but (2) different effects and partially complementary trends on growth characteristics and on the hepatic transcriptome and associated pathways and that (3) only a small number of genes and associated upstream regulators might be involved in passing early diet-induced imprints to adulthood.

MP76-13 EFFECTS OF PERINATAL AND/OR POSTNATAL HIGH-FAT DIET ON TESTICULAR MORPHOLOGY AND SPERM PARAMETERS IN ADULT WISTAR RATS

You have accessJournal of UrologyInfertility: Basic Research, Physiology, Pathophysiology1 Apr 2015MP76-13 EFFECTS OF PERINATAL AND/OR POSTNATAL HIGH-FAT DIET ON TESTICULAR MORPHOLOGY AND SPERM PARAMETERS IN ADULT WISTAR RATS Pamella Campos-Silva, Flavia Fernandes-Lima, Angelo Fernandes-Neto, Diogo B. De Souza, Waldemar S. Costa, Francisco J.B. Sampaio, Fernanda A.M. Nascimento, and Bianca M. Gregorio Pamella Campos-SilvaPamella Campos-Silva More articles by this author , Flavia Fernandes-LimaFlavia Fernandes-Lima More articles by this author , Angelo Fernandes-NetoAngelo Fernandes-Neto More articles by this author , Diogo B. De SouzaDiogo B. De Souza More articles by this author , Waldemar S. CostaWaldemar S. Costa More articles by this author , Francisco J.B. SampaioFrancisco J.B. Sampaio More articles by this author , Fernanda A.M. NascimentoFernanda A.M. Nascimento More articles by this author , and Bianca M. GregorioBianca M. Gregorio More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2798AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The high-fat diet intake during gestation and/or lactation, may cause metabolic, morphological and physiological changes in offspring, such as renal and cardiovascular disease. However, little is discussed about its effects on the testis. Therefore, this study aimed to evaluate the effects of high-fat diet administration during gestation, lactation and/or postnatal period on glycemia, testicular morphology and sperm parameters of Wistar rats at 4 months-old. METHODS Twenty female Wistar rats were fed a control diet (C) or high-fat diet (HF - rich in cholesterol), during pregnancy and lactation. After birth, males offspring were divided into 4 groups as following: C/C, HF/HF (offspring that were maintained with the mother's diet, in postnatal period) and C/HF, HF/C (offspring that changed for high-fat diet or control diet at postnatal period, respectively). Biometric (food intake, body weight) and metabolic parameters (fasting glucose, oral glucose tolerance test) were performed in both dams and pups. At euthanasia, the sperm were collected for sperm parameters evaluation (viability, motility and concentration) and the testis were removed to histomorphometrical analysis. Data were analyzed by unpaired t-test or one-way ANOVA and Bonferroni posttest, considering p<0.05. RESULTS Dams did not present any difference on the body mass gain and energy intake during pregnancy. Also, no difference were found in metabolic parameters at the offspring among the groups. Regarding pups testicular morphology, the high-fat diet intake on the perinatal period (HF/C) promoted an elevation on the seminiferous tubule diameter when compared to another groups (p<0.0001). In contrast, seminiferous epithelium height was lower in all groups, mainly in HF/HF group, that presented a decrease in this parameter in comparison to C/C, HF/C and C/HF groups (p<0.0001). In association, the perinatal and/or postnatal high-fat diet reduced the sperm viability at 4 mo-old (p<0.0001). Furthermore, the HF/C and HF/HF groups presented a reduction in this parameter in comparison to C/HF group (p <0.0001). The sperm concentration analysis was less in HF/HF group than C/C and HF/C groups (p=0.0014) and the motility was similar among the groups. CONCLUSIONS The high-fat diet administration during gestation, lactation and/or postnatal period, did not cause metabolic changes. However, it alters testicular morphology and sperm parameters. These data may suggest disturbances in spermatogenesis in adult life. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e989 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Pamella Campos-Silva More articles by this author Flavia Fernandes-Lima More articles by this author Angelo Fernandes-Neto More articles by this author Diogo B. De Souza More articles by this author Waldemar S. Costa More articles by this author Francisco J.B. Sampaio More articles by this author Fernanda A.M. Nascimento More articles by this author Bianca M. Gregorio More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

Effect of Resveratrol on Cardiovascular and Metabolic Function in Adult Male and Female Offspring Born Intrauterine Growth Restricted

Background Several studies have shown that intrauterine growth restriction (IUGR) predisposes offspring to develop metabolic and cardiovascular disorders in later life. Resveratrol (Resv) has been shown to improve these disorders in adult male IUGR rat offspring. We aim to identify the ability of Resv to prevent cardiovascular and metabolic dysfunction in female IUGR offspring. Methods: Male and female, control or IUGR rat offspring (born from dams exposed to hypoxia; 11% O2 in the last third of pregnancy) were fed a high-fat (HF) diet or a HF diet with Resv (4g/kg of diet) from 3-12 weeks of age. Metabolic and cardiac functions were assessed using a glucose tolerance test, echo MRI and a Langendorff heart system (ischemia/reperfusion (I/R) injury). Cardiac superoxide and endothelial nitric oxide synthase (eNOS) protein levels were assessed using DHE staining and Western blot. Results: Glucose tolerance was impaired in only male IUGR offspring and improved by Resv. In female IUGR offspring, cardiac power after I/R injury was decreased (Control-HF 78.67 ± 3.86 vs IUGR-HF 40.68 ± 11.20 joules.min-1g dry wt-1, P<0.05 ) and improved by Resv (Control-HF+Resv 73.71±2.11; IUGR-HF+Resv 76.65 ± 8.59 joules.min-1g dry wt-1, P<0.05). Similar effects were found in male IUGR offspring. In female IUGR offspring, Resv attenuated superoxide and increased eNOS protein levels in cardiac tissue. Conclusion Prenatal hypoxia and postnatal HF diet exacerbate cardiac and metabolic dysfunction in young adults, which may be improved by Resv treatment. Sex differences in susceptibility to metabolic dysfunction, however, need to be further explored.

Postnatal high-protein diet improves learning and memory in premature rats via activation of mTOR signaling

PurposeThe present study investigated whether a high-protein diet affects spatial learning and memory in premature rats via modulation of mammalian target of rapamycin (mTOR) signaling. MethodsPre- and full-term Sprague-Dawley pups were fed a normal (18% protein) or high-protein (30% protein) diet (HPD) for 6 or 8 weeks after weaning. Spatial learning and memory were tested in the Morris water maze at week 6 and 8. The activation of mTOR signaling pathway components was evaluated by western blotting. ResultsSpatial memory performance of premature rats consuming a normal and HPD was lower than that of full-term rats on the same diet at 6 weeks, and was associated with lower levels of ribosomal protein S6 kinase p70 subtype (p70S6K) and initiation factor 4E-binding protein 1 (4EBP1) phosphorylation in the hippocampus. Spatial memory was improved in 8-week-old premature rats on an HPD as compared to those on a normal diet. Premature rats on an HPD had p70S6K and 4EBP1 phosphorylation levels in the hippocampus that were comparable to those of full-term rats on an HPD. ConclusionLong-term consumption of a protein-rich diet can restore the impairment in learning and memory in pre-term rats via upregulation of mTOR/p70S6K signaling.

Islet cell response to high fat programming in neonate, weanling and adolescent Wistar rats.

High fat programming, by exposure to a high saturated fat diet during fetal and/or lactational life induces metabolic derangements and alters islet cell architecture in neonate and weanling rats. The present study assessed metabolic changes and islet cell dynamics in response to high fat maintenance during specific developmental periods in adolescent rats, with some parameters also studied in neonate and weanling rats. The experimental groups comprised neonates, weanlings and adolescents maintained on a high fat diet during specific periods of fetal, lactational and/or postnatal life. Control neonates, weanlings and adolescents were maintained on a standard laboratory (control or low fat) diet. Fetal high fat programmed (i.e., maintained on a high fat diet exclusively during fetal life) neonates were insulin resistant. Weanlings maintained on a high fat diet throughout fetal and lactational life had increased pancreas weights. Fetal high fat programmed adolescents presented a normal phenotype mimicking the control adolescents. Adolescents maintained on a postnatal high fat diet had increased body weights, hyperglycemia, hyperinsulinemia, hyperleptinemia and insulin resistance displaying beta cell hypertrophy and increased islet cell proliferation. Adolescents maintained on a fetal and postnatal high fat diet had increased body weights, hyperleptinemia, hyperinsulinemia and insulin resistance. High fat programming induces various diabetogenic phenotypes which present at different life stages. The postnatal period from birth to adolescence represents an extension for high fat programming of metabolic disease.

The effects of prenatal undernutrition and postnatal high-fat diet on hypothalamic Kiss1 mRNA and serum leptin levels

Prenatal undernutrition and postnatal overnutrition increase the risk of some metabolic disorders in adulthood, and hypothalamic leptin resistance makes an important contribution to these effects. Leptin plays important roles in the maintenance of reproductive function, and its actions might be partially mediated by kisspeptin, which is a potent positive regulator of gonadotropin-releasing hormone. In this study, the effects of prenatal undernutrition and postnatal overnutrition on reproductive parameters and sexual maturation during the peripubertal period were evaluated. Rats subjected to prenatal undernutrition (IUGR) and fed a postnatal high-fat diet (HFD) (n=7) exhibited 40% higher serum leptin levels and 30% lower hypothalamic Kiss1 (the gene encoding kisspeptin) mRNA levels than those subjected to prenatal undernutrition (IUGR) and fed a normal diet (n=7). No such HFD-induced postnatal alterations were observed in the rats fed a normal diet during the prenatal period (control) (n=7 per group). Although the consumption of the HFD did not affect the serum luteinizing hormone levels or body weight of the IUGR or control rats, it did promote vaginal opening in both groups (evaluated in 14 rats per group). These findings indicate that hypothalamic leptin resistance might occur in IUGR-HFD rats, but these changes do not influence downstream effectors of the reproductive endocrinological system. They also suggest that the relationships between nutritional conditions, body weight, reproductive factors, and sexual maturation are complex.

Infant diet, gender and the development of vagal tone stability during the first two years of life

Postnatal nutrition influences neurodevelopment, but it is not known whether the development of individual differences in physiologic measures is related to variations in early postnatal diet. To address this issue we studied the stability of vagal tone (V)—an index of individual differences in parasympathetic heart rate control—by measuring resting V quarterly during infancy and again at 2years in 146 breast-fed (BF), 143 milk formula-fed (MF), and 137 soy formula-fed (SF) infants. Stability of V across infancy was more consistently significant for BF than formula-fed infants. Stability was similar for boys and girls in BF and SF groups but was generally higher in boys than girls in the MF group. Significant stability between infancy and 2years emerged later in SF than other groups and later in boys than girls. Stability generally peaked between 6 and 9months—a time when postnatal vagal myelination slows and which may represent a pivotal stage in the development of V stability. These findings indicate that infant diet and gender are important modulators of the early development of autonomic state control.