Behavioral Feeding Circuit: Dietary Fat-Induced Effects of Inflammatory Mediators in the Hypothalamus.

Excessive dietary fat intake has extensive impacts on several physiological systems and can lead to metabolic and nonmetabolic disease. In animal models of ingestion, exposure to a high fat diet during pregnancy predisposes offspring to increase intake of dietary fat and causes increase in weight gain that can lead to obesity, and without intervention, these physiological and behavioral consequences can persist for several generations. The hypothalamus is a region of the brain that responds to physiological hunger and fullness and contains orexigenic neuropeptide systems that have long been associated with dietary fat intake. The past fifteen years of research show that prenatal exposure to a high fat diet increases neurogenesis of these neuropeptide systems in offspring brain and are correlated to behavioral changes that induce a pro-consummatory and obesogenic phenotype. Current research has uncovered several potential molecular mechanisms by which excessive dietary fat alters the hypothalamus and involve dietary fatty acids, the immune system, gut microbiota, and transcriptional and epigenetic changes. This review will examine the current knowledge of dietary fat-associated changes in the hypothalamus and the potential pathways involved in modifying the development of orexigenic peptide neurons that lead to changes in ingestive behavior, with a special emphasis on inflammation by chemokines.

Programación fetal / Fetal programming

El término Origen Temprano de las Enfermedades del Adulto explica la aparición temprana de las condiciones anormales cardiovasculares y metabólicas en la vida adulta, mayor riesgo de morbilidad y muerte asociados a factores ambientales, especialmente nutricionales, que actúan en las primeras etapas de la vida. Estas respuestas programadas dependen de la naturaleza del estímulo o noxa, del tiempo de exposición y del momento de ocurrencia de la noxa, pudiendo un solo genotipo original varios fenotipos y estarían condicionadas por criterios críticos en los cuales se desarrollarían cambios a largo plazo pudiendo ser reversibles o no. La Programación Fetal explica que respuestas adaptativas embrionarias y fetales en un ambiente subóptimo genera consecuencias adversas permanentes. La desnutrición, así como la sobrenutrición fetal aumenta el riesgo de desarrollar alteraciones en el peso y composición corporal fetal, y posteriormente obesidad, síndrome metabólico, incremento en la adiposidad, alteración en el metabolismo de la glucosa y / o insulina, alteración del metabolismo lipídico, alteraciones hepáticas y de las cifras tensionales. La impronta genómica es esencial para el desarrollo y defectos en la misma puede originar alteraciones de la identidad parental transmisibles a las siguientes generaciones. Esta programación fetal puede ser explicada por la epigenética, definida como la serie de alteraciones hereditarias de la expresión genética a través de modificaciones del ADN y las histonas centrales sin cambios en la secuencia de ADN. Estas modificaciones epigenéticas alteran la estructura y condensación de la cromatina, afectando la expresión del genotipo y fenotipo. Este artículo desarrolla los aspectos involucrados en la Programación Fetal y los posibles mecanismos sobre la misma(AU)

The term Early Origin of Adult Diseases explains the early onset of abnormal cardiovascular and metabolic conditions in adult life, increased risk of morbidity and death associated with environmental factors, especially nutritional factors, that act in the early stages of life. These programmed responses depend on the nature of the stimulus or noxa, the time of exposure and the moment of occurrence of the noxa, with a single original genotype being able to have several phenotypes and would be conditioned by critical criteria in which long-term changes could develop, reversibles or not. Fetal Programming explains that embryonic and fetal adaptive responses in a suboptimal environment generate permanent adverse consequences. Fetal malnutrition as overnutrition increases the risk of developing alterations in fetal body weight and composition, and subsequently obesity, metabolic syndrome, increased adiposity, impaired glucose and / or insulin metabolism, impaired lipid metabolism, liver disorders and altered blood pressure. The genomic imprint is essential for development and defects in it can cause alterations of the parental identity and are transmitted to the following generations. This fetal programming can be explained by epigenetics, defined as the series of inherited alterations of genetic expression through modifications of DNA and central histones without changes in the DNA sequence. These epigenetic modifications alter the structure and condensation of chromatin, affecting the expression of the genotype and phenotype. This article develops the aspects involved in Fetal Programming and the possible mechanisms on it(AU)

Effects of altered maternal folate and vitamin B12 on neurobehavioral outcomes in F1 male mice.

Maternal folate and vitamin B12 status during pregnancy may influence development of central nervous system (CNS) in the offspring. Very little attention has been paid to understand the combined effects of both the vitamins during pregnancy. The present study was designed to evaluate the biochemical and behavioral outcomes following alterations in folate and vitamin B12 levels in C57BL/6 mice. The female mice were fed with different combinations of folate and vitamin B12 whereas; males were fed with normal diet for 4 weeks. The mice were mated and the pregnant mice received the same diets as before pregnancy. The F1 male mice were further continued on maternal diet for 6 weeks following neurobehavioral and biochemical assessment. The body weight of the F1 male mice was significantly decreased in the mice that received folate and vitamin B12 deficient diet. Altered cognitive functions were observed in the folate and B12 deficient F1 male mice as assessed by Morris water maze and novel object recognition tests. Spontaneous locomotor activity was decreased in F1 male mice fed with folate and B12 deficient diets. Elevated homocysteine levels and decreased hydrogen sulfide levels were also observed in the brain of F1 male mice on folate and B12 deficient diets. However, GSH and GSSG levels were increased in the brain of the animals supplemented with folate deficient diet with different combinations of B12. The study suggests that exposure of female mice to folate and vitamin B12 deficiency during pregnancy effects in-utero development of fetus, which further leads to behavioral anomalies in adult life and is sufficient to cause impaired cognitive behavior in the subsequent generation. Thus, elucidating the role and importance of maternal dietary folate and B12 ratio during pregnancy.

Critical Windows for the Programming Effects of Early-Life Nutrition on Skeletal Muscle Mass.

Skeletal myogenesis begins in the embryo with proliferation and differentiation of muscle progenitor cells that ultimately fuse to form multinucleated myofibers. After midgestation, muscle growth occurs through hypertrophy of these myofibers. The most rapid growth phase occurs in the perinatal period, resulting in the expansion of muscle mass from 25% of lean mass at birth to 40-45% at maturity. These 2 phases of muscle growth are regulated by distinct molecular mechanisms engaged by extracellular cues and intracellular signaling pathways and regulatory networks they activate. Nutrients influence muscle growth by both providing the necessary substrates and eliciting extracellular cues which regulate the signal transduction pathways that control the anabolic processes of the fibers. The uniquely large capacity of immature myofibers for hypertrophy is enabled by a heightened capacity and sensitivity of protein synthesis to feeding-induced changes in plasma insulin and amino acids, and the ability to expand their myonuclear population through proliferation of muscle precursor cells (satellite cells). With maturation, satellite cells become quiescent, limiting myonuclear accretion, and the capacity of the muscles for protein anabolism progressively diminishes. Therefore, the early developmental phases represent critical windows for muscle growth which, if disrupted, result in muscle mass deficits that are unlikely to be entirely recoverable.

[Does Malnutrition during Fetal Life Have a Potential to Be a Precipitating Factor for Developmental Disorders?]

OBJECTIVES: The developmental origins of health and disease paradigm (DOHaD) is a concept that fetal environmental factors affect adult phenotypes. We performed experiments to evaluate the DOHaD theory in developmental disorders using mouse models. METHODS: In vitro fertilization and embryo transfer techniques were used for mouse production. The AIN93G-control diet, which contains 20% protein (CD), 5% protein-restricted diet (PR), and PR with supplemental folic acid (FA) were provided as experimental diets to mothers. The body weights (BWs) of mothers and offspring, and the blood-clinical biochemistry results of mothers were examined. In addition, gene expression and genomic methylation in the brain of adult offspring and behavioral phenotypes of adult offspring were examined. RESULTS: Pregnant mothers that consumed the protein-restricted diets, namely, PR and FA, exhibited reduction in BW. The values of protein-related parameters determined by blood-clinical biochemistry decreased in the PR fed groups. The BWs of neonates and adult offspring did not change. The offspring exposed to maternal hyponutrition exhibited increased activity in the home cage and enhanced fear and anxiety-like behavior. The adult offspring of the PR-fed group and FA-fed groups exhibited different patterns of mRNA expression and genomic methylation in the brain. CONCLUSIONS: The maternal PR diet affected the progenies' behavioral phenotypes and epigenetic outcomes in the brain. However, the behavioral changes induced by maternal protein restriction were very slight. Hence, interactions between several genetic factors and environmental exposures such as maternal malnutrition may cause developmental and psychiatric disorders.

Effects of perinatal protein malnutrition and fenfluramine action on food intake and neuronal activation in the hypothalamus and raphe nuclei of neonate rats.

In neonatal rats, hunger and satiety responses occur particularly via dehydration and gastric distention, respectively. The control of food intake in newborns is yet to be fully consolidated, particularly with respect to the participation of the hypothalamic nuclei and their relationship with the serotonergic pathway. Moreover, it is unclear how the environmental stressors in early life, like undernutrition, interfere in these events. Therefore, this study examined the serotonin-system's impact on food intake in rat neonates at postnatal day (P) 10 and P18 and the manner in which protein undernutrition during pregnancy and lactation interferes in this behavior. To accomplish this, Wistar rats were used, nutritionally manipulated by a diet having two protein levels, (8% and 17%) during pregnancy and lactation, to form the Control (n=10) and Low protein groups (n=10). At 10 and 18 postnatal days pups received an acute dose of fenfluramine (3mg/kg) or saline (0.9% NaCl) and subjected to milk consumption testing and then perfused to obtain the brains for the analysis of cell activation of the immunoreactive c-Fos in the hypothalamic and raphe nuclei. At 10days a reduction in weight gain was observed in both groups. On comparison of the neuronal activation for the paraventricular nucleus, an increased activation in response to fenfluramine was observed. At 18days, the weight gain percentage differed between the groups according to the nutritional manipulation, in which the control animals had no significant change while the undernourished presented increased weight gain with the use of fenfluramine. The marking of c-Fos in response to fenfluramine in the hypothalamic and raphe nuclei revealed, an especially lower activation of the PVN, MnR and DR compared intra-group. However when evaluating the effect of undernutrition, marking activation was observed to increase in all the nuclei analyzed, in the hypothalamus and raphe. Data from this study indicate that the action of serotonin via food intake in the neonates may have been delayed by early protein undernutrition.

Projected future distribution of date palm and its potential use in alleviating micronutrient deficiency.

BACKGROUND: Micronutrient deficiency develops when nutrient intake does not match nutritional requirements for maintaining healthy tissue and organ functions which may have long-ranging effects on health, learning ability and productivity. Inadequacy of iron, zinc and vitamin A are the most important micronutrient deficiencies. Consumption of a 100 g portion of date flesh from date palm (Phoenix dactylifera L.) has been reported to meet approximately half the daily dietary recommended intake of these micronutrients. This study investigated the potential distribution of P. dactylifera under future climates to address its potential long-term use as a food commodity to tackle micronutrient deficiencies in some developing countries. RESULTS: Modelling outputs indicated large shifts in areas conducive to date palm cultivation, based on global-scale alteration over the next 60 years. Most of the regions suffering from micronutrient deficiencies were projected to become highly conducive for date palm cultivation. CONCLUSIONS: These results could inform strategic planning by government and agricultural organizations by identifying areas to cultivate this nutritionally important crop in the future to support the alleviation of micronutrient deficiencies.

Effects of Pre-Natal Vitamin D Supplementation with Partial Correction of Vitamin D Deficiency on Early Life Healthcare Utilisation: A Randomised Controlled Trial.

BACKGROUND: Some observational studies have suggested that higher prenatal Vitamin D intake may be associated with improved health outcomes in childhood. However there have been mixed results in this area with some negative studies, especially for effects on atopic and respiratory outcomes. We examined the effect of prenatal Vitamin D on healthcare utilisation in the first three years of life. METHODS: In an ethnically stratified randomised controlled trial conducted at St Mary's Hospital London, 180 women at 27 weeks gestation were allocated to no Vitamin D, 800 IU ergocalciferol daily until delivery, or a single oral bolus of 200,000 IU cholecalciferol. Participants were randomised in blocks of 15 using computer-generated numbers and investigators were blinded to group assignment. Supplementation increased maternal and cord blood 25(OH) vitamin D concentrations, but levels remained lower than current recommendations. Primary health economic outcome was overall cost of unscheduled healthcare utilisation in the first three years of life as documented in the child's electronic health record. Secondary outcomes included cost attributable to: primary and secondary healthcare visits, respiratory and atopic complaints, cost in years 1, 2 and 3 of life and cost and frequency of prescribed medication. All costs were calculated as pounds sterling. Differences between groups were analysed using unpaired t-test or Mann-Whitney U test, and analysis of variance for adjusted analyses. RESULTS: We assessed 99/180 (55%) complete electronic health records, control (n = 31), daily (n = 36) and bolus (n = 32). We found no difference in total healthcare utilisation costs between the control and daily (mean difference in costs in pounds sterling 1.02, 95%CI -1.60, 1.65; adjusted 1.07, 95%CI -1.62, 1.86) or control and bolus groups (mean difference -1.58, 95%CI -2.63, 1.06; adjusted -1.40, 95%CI -2.45, 1.24). There were no adverse effects of supplementation reported during the trial. CONCLUSIONS: We found no evidence that prenatal vitamin D supplementation from 27 weeks gestation to delivery, at doses which failed to completely correct maternal vitamin D deficiency, influence overall healthcare utilisation in children in the first 3 years. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN68645785.

Let-7 miRNA profiles are associated with the reversal of left ventricular hypertrophy and hypertension in adult male offspring from mothers undernourished during pregnancy after preweaning growth hormone treatment.

Maternal undernutrition (UN) is known to cause cardiac hypertrophy, elevated blood pressure, and endothelial dysfunction in adult offspring. Maternal UN may also lead to disturbances in GH regulation in offspring. Because GH plays a key role in cardiac development, we used a model of maternal UN to examine the effects of neonatal GH treatment on cardiac hypertrophy, cardiac micro RNA (miRNA) profiles, and associated gene regulation in adult offspring. Female Sprague-Dawley rats were fed either a standard control diet (CON) or 50% of CON intake throughout pregnancy (UN). From neonatal day 3 until weaning (d 21), CON and UN pups received either saline (S) (CON-S, UN-S) or GH (2.5 µg/g·d) (CON-GH, UN-GH). Heart structure was determined by hematoxylin and eosin staining, and miRNA was isolated from cardiac tissue and miRNA expression analyzed using Cardiovascular miRNA gene Arrays (SABiosciences Ltd). Maternal UN caused marked increases in cardiac hypertrophy and left ventricular cardiomyocyte area, which were reversed by preweaning GH treatment. Systolic blood pressure was increased in UN-S groups and normalized in UN-GH groups (CON-S 121 ± 2 mmHg, CON-GH 115 ± 3 mm Hg, UN-S 146 ± 3 mmHg, and UN-GH 127 ± 2 mmHg). GH treatment during early development facilitated a reversal of pathological changes in offspring hearts caused by UN during pregnancy. Specific cardiac miRNA profiles were exhibited in response to maternal UN, accompanied by up-regulation of the lethal-7 (LET-7) miRNA family in GH-treated offspring. miRNA target analysis revealed a number of genes associated with inflammation and cardiovascular development, which may be involved in the altered cardiac function of these offspring. Up-regulation of the LET-7 family of miRNAs observed in GH groups may mediate the reversal of cardiac hypertrophy observed in adult offspring males of UN mothers.

The first 500 days of life: policies to support maternal nutrition.

BACKGROUND: From conception to 6 months of age, an infant is entirely dependent for its nutrition on the mother: via the placenta and then ideally via exclusive breastfeeding. This period of 15 months--about 500 days--is the most important and vulnerable in a child's life: it must be protected through policies supporting maternal nutrition and health. Those addressing nutritional status are discussed here. OBJECTIVE AND DESIGN: This paper aims to summarize research on policies and programs to protect women's nutrition in order to improve birth outcomes in low- and middle-income countries, based on studies of efficacy from the literature, and on effectiveness, globally and in selected countries involving in-depth data collection in communities in Ethiopia, India and Northern Nigeria. Results of this research have been published in the academic literature (more than 30 papers). The conclusions now need to be advocated to policy-makers. RESULTS: The priority problems addressed are: intrauterine growth restriction (IUGR), women's anemia, thinness, and stunting. The priority interventions that need to be widely expanded for women before and during pregnancy, are: supplementation with iron-folic acid or multiple micronutrients; expanding coverage of iodine fortification of salt particularly to remote areas and the poorest populations; targeted provision of balanced protein energy supplements when significant resources are available; reducing teenage pregnancies; increasing interpregnancy intervals through family planning programs; and building on conditional cash transfer programs, both to provide resources and as a platform for public education. All these have known efficacy but are of inadequate coverage and resourcing. The next steps are to overcome barriers to wide implementation, without which targets for maternal and child health and nutrition (e.g. by WHO) are unlikely to be met, especially in the poorest countries. CONCLUSIONS: This agenda requires policy decisions both at Ministry and donor levels, and throughout the administrative system. Evidence-based interventions are established as a basis for these decisions, there are clear advocacy messages, and there are no scientific reasons for delay.

Role of prenatal undernutrition in the expression of serotonin, dopamine and leptin receptors in adult mice: implications of food intake.

Perturbations in the levels of serotonin expression have a significant impact on behavior and have been implicated in the pathogenesis of several neuropsychiatric disorders including anxiety, mood and appetite. Fetal programming is a risk factor for the development of metabolic diseases during adulthood. Moreover, previous studies have shown that serotonin (5­HT), dopamine and leptin are important in energy balance. In the present study, the impact of maternal malnutrition­induced prenatal undernutrition (UN) was investigated in mice and the expression of 5­HT1A, dopamine (D)1, D2 and Ob­Rb receptors was analyzed in the hypothalamus during adulthood. The UN group showed a low birth weight compared with the control group. With regard to receptor expression, 5­HT1A in the UN group was increased in the hypothalamus and D1 was reduced, whereas D2 showed an increase from postnatal day (P)14 in the arcuate nucleus. Ob­Rb receptor expression was increased in the hypothalamus at P14 and P90. These observations indicated that maternal caloric restriction programs a postnatal body weight gain in offspring with an increased food intake in early postnatal life which continues into adulthood. In addition, UN in mice was found to be affected by Ob­Rb, 5­HT1A and D1/2 receptor expression, indicating that these observations may be associated with hyperphagia and obesity.

Nutritional models of foetal programming and nutrigenomic and epigenomic dysregulations of fatty acid metabolism in the liver and heart.

Barker's concept of 'foetal programming' proposes that intrauterine growth restriction (IUGR) predicts complex metabolic diseases through relationships that may be further modified by the postnatal environment. Dietary restriction and deficit in methyl donors, folate, vitamin B12, and choline are used as experimental conditions of foetal programming as they lead to IUGR and decreased birth weight. Overfeeding and deficit in methyl donors increase central fat mass and lead to a dramatic increase of plasma free fatty acids (FFA) in offspring. Conversely, supplementing the mothers under protein restriction with folic acid reverses metabolic and epigenomic phenotypes of offspring. High-fat diet or methyl donor deficiency (MDD) during pregnancy and lactation produce liver steatosis and myocardium hypertrophy that result from increased import of FFA and impaired fatty acid ß-oxidation, respectively. The underlying molecular mechanisms show dysregulations related with similar decreased expression and activity of sirtuin 1 (SIRT1) and hyperacetylation of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α). High-fat diet and overfeeding impair AMPK-dependent phosphorylation of PGC-1α, while MDD decreases PGC-1α methylation through decreased expression of PRMT1 and cellular level of S-adenosyl methionine. The visceral manifestations of metabolic syndrome are under the influence of endoplasmic reticulum (ER) stress in overnourished animal models. These mechanisms should also deserve attention in the foetal programming effects of MDD since vitamin B12 influences ER stress through impaired SIRT1 deacetylation of HSF1. Taken together, similarities and synergies of high-fat diet and MDD suggest, therefore, considering their consecutive or contemporary influence in the mechanisms of complex metabolic diseases.

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

OBJECTIVE: The 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. METHODS: Pregnant 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. RESULTS: The 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. CONCLUSION: GTE 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.

Thyroid function in pregnant women: iodine deficiency after iodine enrichment program.

OBJECTIVE: Significant changes in thyroid function occur during pregnancy which can complicate the interpretation of thyroid function tests. Therefore, normative gestational related reference ranges for thyroid hormones tests are required. The aim of this study was to determine the reference ranges for free triiodothyronine (FT3), free thyroxin (FT4) and thyroid stimulating hormone (TSH) in Iranian pregnant women. METHODS: This study was a cross-sectional observational study conducted in the Obstetrics and Gynecology department, Akbarabadi University Hospital. A single blood sample from 584 pregnant women was analyzed for thyroid function. Serum levels of TSH, FT4, FT3, total T4 (TT4), T3 resin uptake (T3RU) and anti-thyroid peroxidase antibody (TPO Ab) were measured. Urinary iodine was determined in some cases. Reference intervals based on 2.5th and 97.5th percentiles were calculated. RESULTS: The composition of reference population comprising 584 women included 162 in first trimester and 422 in the third trimester. The 2.5th and 97.5th percentiles values were used to determine the reference ranges for FT3, FT4, TT4, T3RU and TSH. These values were T3 1.4 and 2.9 pmol/L, FT4 7.1 and 18 pmol/L, TT4 7.2 and 13.5 µg/dL and TSH 0.5 and 3.9 µg/L, respectively. The level of urinary iodine in 80.5% of the subjects was less than normal. CONCLUSIONS: Serum levels of thyroid hormones are different in Iranian population that could be due to racial differences or differences in iodine intake.

Monitoring and effects of iodine deficiency in pregnancy: still an unsolved problem?

Iodine is required for the production of thyroid hormone. Thyroid hormone affects many metabolic processes in the body, including maturation of the central nervous system. In early pregnancy, the fetus is dependent on maternal thyroid hormone for normal brain development. If iodine deficiency leads to inadequate production of thyroid hormone during pregnancy, irreversible brain damage can result in the fetus. Therefore, achieving adequate iodine nutrition during pregnancy is an important public health objective. Although there have been tremendous gains over the last several decades in our understanding of the effects of iodine deficiency in pregnancy and how to combat them, a number of questions remain about how best to monitor the iodine status of pregnant populations, the effects of mild to moderate iodine deficiency on maternal and child outcomes, the safe upper limit of daily iodine intake in pregnant women and the risks and benefits of iodine supplementation for mildly iodine-deficient pregnant women.

Physiopathology of intrauterine growth retardation: from classic data to metabolomics.

It is well known that adverse conditions during intrauterine life, such as intrauterine growth restriction (IUGR), can result in permanent changes in the physiology and metabolism of the newborn, which in turn leads to an increased risk of disease in adulthood (fetal origin of adult disease hypothesis). In the first part of this review the epidemiological studies in which a correlation between low birth weight and chronic pathologies in adulthood was observed are reported. The second part of the review is focused on metabolomics studies that have revealed an altered metabolism in IUGR patients compared to controls. Together with more classic biomarkers of IUGR, such as endothelin-1, leptin, protein S100B and visfatin, the new holistic metabolomics approach has assumed a crescent role in the identification of disorders in the neonatal metabolic profile, determined by the interconnection of the different processes.

Desnutrição perinatal e o controle hipotalâmico do comportamento alimentar e do metabolismo do músculo esquelético / Perinatal undernutrition and hypothalamic control of food intake and energy metabolism in the skeletal muscle

A deficiência de nutrientes durante os períodos críticos do desenvolvimento tem sido associada com maior risco para desenvolver obesidade e diabetes Mellitus na vida adulta. Um dos mecanismos propostos refere-se à regulação do comportamento alimentar e às alterações do metabolismo energético do músculo esquelético. Recentemente, tem sido proposta a existência de uma comunicação entre o hipotálamo e o músculo esquelético a partir de sinais autonômicos que podem explicar as repercussões da desnutrição perinatal. Assim, esta revisão tem como objetivo discutir as repercussões da desnutrição perinatal sobre o comportamento alimentar e o metabolismo energético muscular e a comunicação existente entre o hipotálamo e o músculo via sinais adrenérgicos. Foram utilizadas as bases de dados MedLine/PubMed, Lilacs e Bireme, com publicações entre 2000 e 2011. Os termos de indexação utilizados foram: feeding behavior, energy metabolism, protein malnutrition, developmental plasticity, skeletal muscle e autonomic nervous system. Concluiu-se que a desnutrição perinatal pode atuar no controle hipotalâmico do comportamento alimentar e no metabolismo energético muscular, e a comunicação hipotálamo-músculo pode favorecer o desenvolvimento de obesidade e comorbidades durante o desenvolvimento.

Undernutrition during the critical period of development has been associated with susceptibility to obesity and diabetes Mellitus in adulthood. One of the underlying mechanisms can be related with the relationship between the food intake and the metabolism of skeletal muscle. A communication between the hypothalamus and skeletal muscle has been recently proposed, which can explain the repercussion of perinatal undernutrition. Thus, this review aims mainly to discuss the repercussions of perinatal undernutrition on food intake and skeletal muscle metabolism by adrenergic signals. Articles published from 2000 to 2011 were searched in the Medline/Pubmed, Lilacs and Bireme databases using the following keywords: feeding behavior, energy metabolism, protein malnutrition, developmental plasticity, skeletal muscle and autonomic nervous system. In conclusion, perinatal undernutrition can alter the hypothalamic control of food intake and skeletal muscle metabolism. Additionally, communication between the hypothalamus and skeletal muscle can promote the development of obesity and associated diseases.

Iron in pregnancy: How do we secure an appropriate iron status in the mother and child?

Iron deficiency and iron deficiency anemia (IDA) during pregnancy are risk factors for preterm delivery, prematurity, and small for gestational age birth weight. Iron deficiency has a negative effect on intelligence and behavioral development in the infant. It is essential to prevent iron deficiency in the fetus by preventing iron deficiency in the pregnant woman. The requirements for absorbed iron increase during pregnancy from ∼1.0 mg/day in the first trimester to 7.5 mg/day in the third trimester. More than 90% of Scandinavian women of reproductive age have a dietary iron intake below the recommended 15 mg/day. Among nonpregnant women of reproductive age, ∼40% have plasma ferritin ≤30 µg/l, i.e. an unfavorable iron status with respect to pregnancy. An adequate iron status during pregnancy implies body iron reserves ≥500 mg at conception, but only 15-20% of women have iron reserves of such a magnitude. Iron supplements during pregnancy reduce the prevalence of IDA. In Europe, IDA can be prevented by a general low-dose iron prophylaxis of 30-40 mg ferrous iron taken between meals from early pregnancy to delivery. In affluent societies, individual iron prophylaxis tailored by the ferritin concentration should be preferred to general prophylaxis. Suggested guidelines are: ferritin >70 µg/l, no iron supplements; ferritin 31-70 µg/l, 30-40 mg ferrous iron per day, and ferritin ≤30 µg/l, 60-80 mg ferrous iron per day. In women with ferritin <15 µg/l, i.e. depleted iron reserves and possible IDA, therapeutic doses of 100 mg ferrous iron per day should be advised.

Antenatal taurine supplementation for improving brain ultrastructure in fetal rats with intrauterine growth restriction.

Changes in brain ultrastructure of fetal rats with intrauterine growth restriction (IUGR) were explored and the effects of antenatal taurine supplementation on their brain ultrastructure were determined. Fifteen pregnant rats were randomly divided into three groups: control group, IUGR model group and IUGR group given antenatal taurine supplements. Taurine was added to the diet of the taurine group at a dose of 300 mg/kg/d from 12 days after conception until natural delivery. Transmission electron microscopy was used to observe ultrastructural changes in the brains of the newborn rats. At the same time, brain cellular apoptosis was detected using TUNEL, and the changes in protein expression of neuron specific enolase and glial fibrillary acidic protein were analyzed using immunohistochemistry. The results showed that: 1) The average body weight and cerebral weight were significantly lower in the IUGR group than in the control group (p<0.01) and both of them were less so after taurine was supplemented (p<0.01). 2) Transmission electron microscopy revealed that brain cortex structures were sparse IUGR rats, showing many scattered apoptotic cells, decreased numbers of synapses, lower glial cell proliferation, and fewer neurons, more sparsely arranged, while these factors were significantly improved with taurine supplementation. 3) The results of TUNEL showed that the counts of apoptotic brain cells in IUGR groups were significantly increased from those in control groups and that taurine could significantly decrease brain cell apoptosis (p<0.001). 4) The results of immunohistochemistry showed that antenatal taurine-supplementation could significantly increase the counts of neuron specific enolase and glial fibrillary acidic protein immunoreactive cells in fetal rats with IUGR (p<0.001). It can be concluded that it IUGR has a significant detrimental influence on the development of fetal rat brains, and antenatal supplement of taurine can significantly improve the IUGR fetal brain development.