Nutritional Insult Research Articles

Impact of fetal and neonatal malnutrition on the onset of puberty and associated noncommunicable disease risks

BackgroundFetal and neonatal malnutrition impacts the timing of the onset of puberty. The timing of puberty onset has been shown to be a rough indicator of noncommunicable disease (NCD) risk. Recent advances in understanding the various inter-related neurochemical and genetic controls underpinning puberty onset have shed new light on these interesting and important phenomena. These studies have suggested that developmental trajectory is set very early by epigenetic mechanisms that serve to adjust phenotype to environment.ObjectiveThe aims of this article are to review the most recent research into the proximate mechanisms that initiate puberty; to explore how the activation of those mechanisms could be affected by nutritional cues received during fetal and neonatal life; and, finally, to briefly explore the ramifications for public health.MethodsAn extensive literature review was performed using PubMed (1950 to September 2010) and Google Scholar (1980 to September 2010) using the search terms “puberty onset”, “perinatal”, and “neonatal malnutrition”. English language, original research, and review articles were examined; pertinent citations from these articles were also assessed.ResultsLiterature detailing biochemical pathways and evolutionary explanations of human puberty itself led quickly to a noteworthy connection between neonatal malnutrition, puberty onset, and NCD risk. A strong connection was found between maternal malnutrition during critical windows (followed by catch-up growth in childhood) and an accelerated onset of puberty. Children subject to early nutritional insult not only are likely to undergo puberty earlier but also show an increase in their risk of developing NCDs in later life. Several authors have suggested that this relationship may show potential as an early proxy indicator of susceptibility to these types of diseases, which are an increasing concern in both affluent and developing countries.ConclusionsMore attention should be paid to fetal and neonatal nutrition and puberty onset if we are to meaningfully curb the troubling growth of NCDs now and in the future. Efforts to improve maternal conditions among vulnerable poor groups as well as more affluent groups worldwide should be explored, especially among groups undergoing rapid nutritional transition.

Nutritional programming of pancreatic β-cell plasticity

Nutritional insufficiency during pregnancy has been shown to alter the metabolism of the offspring and can increase the risk of type 2 diabetes. The phenotype in the offspring involves changes to the morphology and functional capacity of the endocrine pancreas, and in the supporting islet microvasculature. Pancreatic β-cells possess a plastic potential and can partially recover from catastrophic loss. This is partly due to the existence of progenitors within the islets and the ability to generate new islets by neogenesis from the pancreatic ducts. This regenerative capacity is induced by bone marrow-derived stem cells, including endothelial cell progenitors and is associated with increased angiogenesis within the islets. Nutritional insults in early life, such as feeding a low protein diet to the mother, impair the regenerative capacity of the β-cells. The mechanisms underlying this include a reduced ability of β-cells to differentiate from the progenitor population, changes in the inductive signals from the microvasculature and an altered presence of endothelial progenitors. Statin treatment within animal models was associated with angiogenesis in the islet microvasculature, improved vascular function and an increase in β-cell mass. This demonstrates that reversal of the impaired β-cell phenotype observed following nutritional insult in early life is potentially possible.

Perinatal nutritional programming of health and metabolic adult disease

Data indicate that perinatal nutritional insults not onlyhave short-term consequences on the growth velocity of the fetus/neonate but also sensitize to the development of metabolic adult diseases. The pathophysiological mechanisms involved in the so-called "Developmental Origin of Health and Adult Diseases" are still largely unknown and depend on the type of alteration (nutritional, psychological, endocrine disruptors, etc.), its intensity and duration, species, sex and the time during which it is applied. Perinatal stress, via disturbances of both hypothalamo-pituitary-adrenal (HPA) axis and sympatho-adrenal-system (SAS), as well as brain-adipose axis and pancreas alterations could play a crucial role. Interestingly, it has been demonstrated that perinatal insults may be transmitted transgenerationally, suggesting that these long-term consequences may be inherited via epigenetic mechanisms. Finally, since the placenta has been demonstrated to be sensitive to perinatal nutritional manipulations, the identification of placental markers may thus represent an important new avenue to identify the more susceptible babies prone to developing metabolic diseases.

Effects of sex, litter size and periconceptional ewe nutrition on offspring behavioural and physiological response to isolation

Maternal periconceptional undernutrition alters fetal hypothalamic–pituitary–adrenal (HPA) axis development. However, the effects of this early nutritional insult on postnatal HPA axis function and stress-related behaviours are unknown. We investigated in sheep the effects of different periods of undernutrition, and of sex and litter size, on offspring behavioural and cortisol responses to isolation stress. We studied four nutritional groups: controls well nourished throughout pregnancy ( n = 39), or ewes undernourished (UN, 10–15% body weight reduction) before mating (−60 to 0 d, n = 26), after mating (−2 to + 30 d, n = 20) or both (−60 to + 30 d, n = 36). At 4 and 18 months of age, offspring were isolated for 5 min, their behaviour video recorded, and plasma cortisol concentrations measured. Offspring of all undernourished groups demonstrated 50% fewer escape attempts than controls at 4 months of age, and offspring of UN−60 + 30 ewes had 20% lower plasma cortisol area under the curve in response to isolation at 18 months. Females had higher cortisol concentrations and vocalised more than males at 4 and 18 months, and were more active at 18 months. After isolation, UN−2 + 30 males had higher cortisol concentrations than UN−2 + 30 females whereas in all other groups males had lower concentrations than females. Singleton males made more escape attempts than females, whereas in twins females made more escape attempts than males. These findings suggest that maternal periconceptional undernutrition in sheep can suppress behavioural reactions and cortisol secretion in response to isolation stress in the offspring into adulthood, and that these effects differ between males and females.

The Developmental Origins, Mechanisms, and Implications of Metabolic Syndrome1–3

Metabolic syndrome (MetS) represents a combination of cardio-metabolic risk determinants, including central obesity, insulin resistance, glucose intolerance, dyslipidemia, hypertension, hyperinsulinemia, and microalbuminuria. The prevalence of MetS is rapidly increasing worldwide, largely as a consequence of the ongoing obesity epidemic. Environmental factors during periods early in development have been shown to influence the susceptibility to develop disease in later life. In particular, there is a wealth of evidence from both epidemiological and animal studies for greater incidence of features of MetS as a result of unbalanced maternal nutrition. The mechanisms by which nutritional insults during a period of developmental plasticity result in a MetS phenotype are now beginning to receive considerable scientific interest. This review focuses on recent data regarding these mechanisms, in particular the epigenetic and transcriptional regulation of key metabolic genes in response to nutritional stimuli that mediate persistent changes and an adult MetS phenotype. A continued and greater understanding of these mechanisms will eventually allow specific interventions, with a favorable impact on the global incidence of cardiovascular disease and type 2 diabetes in the future.

Maternal undernutrition and endocrine development

Maternal undernutrition, whether it occurs before conception, throughout gestation or during lactation, may lead to physiological adaptations in the fetus that will affect the health of the offspring in adult life. The timing, severity, duration and nature of the maternal nutritional insult may affect the offspring differently. Other factors determining outcome following maternal undernutrition are fetal number and gender. Importantly, effects of maternal undernutrition may be carried over into subsequent generations. This review examines the endocrine pathways disrupted by maternal undernutrition that affect the long-term postnatal health of the offspring. Maternal and childhood undernutrition are highly prevalent in low- and middle-income countries, and, in developed countries, unintentional undernutrition may arise from maternal dieting. It is, therefore, important that we better understand the mechanisms driving the long-term effects of maternal undernutrition, as well as identifying treatments to ameliorate the associated mortality and morbidity.

Safety Nets Can Help Address the Risks to Nutrition from Increasing Climate Variability ,

Models of climate change predict increased variability of weather as well as changes in agro-ecology. The increased variability will pose special challenges for nutrition. This study reviews evidence on climate shocks and nutrition and estimates the economic consequences in terms of reduced schooling and economic productivity stemming from nutritional insults in childhood. Panel data covering up to 20 y indicate that that short-term climate shocks have long-term impacts on children that persist, often into their adult lives. Other studies document the potential for relief programs to offset these shocks providing that the programs can be implemented with flexible financing, rapid identification of those affected by the shock, and timely scale-up. The last of these presumes that programs are already in place with contingency plans drawn up. Arguably, direct food distribution, including that of ready-to-use therapeutic food, may be part of the overall strategy. Even if such programs are too expensive for sustainable widespread use in the prevention of malnutrition, scalable food distribution programs may be cost effective to address the heightened risk of malnutrition following weather-related shocks.

Epigenetic changes in gene expression: focus on “The liver X-receptor gene promoter is hypermethylated in a mouse model of prenatal protein restriction”

the term epigenetics was first coined in 1942 by Waddington ([20][1]) to describe the interaction of genes with their environment during development that gives rise to a phenotype. Today, the term epigenetics is used when describing a phenotype that occurs in a manner outside conventional genetic

Abstract: P1341 EVALUATION OF SERUM LEPTIN IN HEALTHY SUBJECTS

In this study, we contrasted the hypothesis that maternal diet during pregnancy has an impact on fetal metabolic programming through changes in liver mitochondrial DNA (mtDNA) content and transcriptional activity of Ppargc1a and that these effects are sex specific.Rats were fed either high-fat (HFD) or standard chow diet (SCD) during gestation and lactation. The resulting adult male and female offspring were fed either HFD or SCD for an 18-week period, generating eight experimental groups.Maternal HFD feeding during pregnancy is associated with a decreased liver mtDNA copy number (P<.008). This effect was independent of the offspring sex or diet, and was significantly associated with fatty liver when dams were fed HFD (P<.05, adjusted by homeostasis model assessment of insulin resistance, HOMA-IR). We also found that maternal HFD feeding results in a male-specific significant reduction of the liver abundance of Ppargc1a mRNA (P<.004), which significantly impacted peripheral insulin resistance. Liver expression of Ppargc1a was inversely correlated with HOMA-IR (R=−0.53, P<.0003). Only male offspring exposed to a chronic metabolic insult in adult life were insulin resistant and hyperleptinemic, and showed abnormal liver and abdominal fat accumulation. Liver abundance of Tfam, Nrf1, Hnf4a, Pepck and Ppparg mRNA was not associated with maternal programming. In conclusion, maternal high-fat diet feeding during pregnancy programs liver mtDNA content and the transcriptional activity of Ppargc1a, which strongly modulates, in a sex-specific manner, glucose homeostasis and organ fat accumulation in adult life after exposure to a nutritional insult.

Fetal nutritional status: diagnosis and future perspectives

Fetal nutritional status: diagnosis and future perspectives

Developmental programming of sex-dependent alterations in lipid metabolism: a role for long-term, sex-specific alterations in LDL-receptor expression. Focus on “Developmental programming of lipid metabolism and aortic vascular function in C57BL/6 mice: a novel study suggesting an involvement of LDL-receptor”

the nobel prize in physiology or medicine was awarded to Brown and Goldstein in 1985 for their discovery of the low-density lipoprotein (LDL) receptor and its importance in the regulation of cholesterol metabolism ([2][1]). Cholesterol, an essential component of the mammalian cell membrane, is

Exercise: Adolescent Menstrual Dysfunction and Skeletal Problems

ABSTRACT Exercise is beneficial for adolescents since it increases bone mineral density (BMD) and fitness. Excessive exercise is associated with unique risk of menstrual dysfunction and skeletal problems in adolescent girls. Hypothalamic dysfunction has the key role in menstrual dysfunction and metabolic aberrations associated with nutritional insult may be the primary factor affecting low bone density in these adolescent girls. Proper physical examination and screening for eating disorder is required for the diagnosis. Treatment should be aimed at correcting metabolic abnormalities than correcting estrogen deficiency.

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

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

Nutritional anaemia dysregulates endocrine control of fetal growth

Severe anaemia is associated with increased low birth weight and Barker's hypothesis of 'fetal origins' proposes that a nutritional insult during critical periods of development results in adaptations that predispose individuals to adult onset diseases. We hypothesize that endocrine alterations may occur in the maternal-fetal milieu as a consequence of nutritional anaemia during pregnancy. We examined the quantitative variations in hormonal profiles in paired maternal and cord blood samples obtained from mothers and their neonates who were classified based on maternal anaemia status. Our results show that: (1) 74.6 % of the mothers enrolled in the study were anaemic, of which 85.2 % had moderate anaemia and 14.7 % had severe anaemia; (2) anthropometric parameters measured in the mothers indicate that severely anaemic mothers had a significantly low pre- and post-pregnancy weight, a significantly decreased maternal fundal height and abdominal circumference; (3) anthropometric measures in the neonates born to severely anaemic mothers show a significant reduction in ponderal index, birth weight and placental weight; (4) significant increase in both maternal, fetal insulin-like growth factor 1, ferritin levels and increased maternal erythropoietin levels were observed with an increase in severity of anaemia; (5) decreased T3 and increased prolactin levels were observed in the maternal blood of severely anaemic mothers as compared with the control group. An insight into the endocrine modulation to overcome a growth disadvantage due to nutritional anaemia in pregnancy may lead to a better understanding of fetal adaptations invoked when the maternal-placental nutrient supply fails to meet the fetal nutrient demand.

Maternal nutrition, intrauterine programming and consequential risks in the offspring

It is traditionally believed that genetic susceptibility and adult faulty lifestyle lead to type 2 diabetes, a chronic non-communicable disease. The "Developmental Origins of Health and Disease" (DOHaD) model proposes that the susceptibility to type 2 diabetes originates in the intrauterine life by environmental fetal programming, further exaggerated by rapid childhood growth, i.e. a biphasic nutritional insult. Both fetal under nutrition (sometimes manifested as low birth weight) and over nutrition (the baby of a diabetic mother) increase the risk of future diabetes. The common characteristic of these two types of babies is their high adiposity. An imbalance in nutrition seems to play an important role, and micronutrients seem particularly important. Normal to high maternal folate status coupled with low vitamin B(12) status predicted higher adiposity and insulin resistance in Indian babies. Thus, 1-C (methyl) metabolism seems to play a key role in fetal programming. DOHaD represents a paradigm shift in the model for prevention of the chronic non-communicable diseases.

Augmented β cell loss and mitochondrial abnormalities in sucrose-fed GK rats

Progressive decline of islet beta cell mass is a hallmark of type 2 diabetes, where nutritional insults are invoked in the pathologic process. Its detailed mechanisms are, however, incompletely understood. We explored the effect of sucrose diet on mitochondria in Goto Kakizaki (GK) rats, a spontaneously diabetic model. Six-week-old male GK rats were given 30% sucrose orally for 2 weeks. Normal Wistar rats fed with sucrose served as controls. Compared to untreated GK rats, sucrose-fed GK rats showed severe degeneration and death of beta cells with disrupted and swollen mitochondria and a greater beta cell loss. Submicroscopic analysis disclosed a smaller mean volume and a greater number of mitochondria in beta cells in GK rats compared to those in Wistar rats. Mitochondria in sucrose-fed GK rats were 2.4-fold greater in mean volume than those in untreated state. Without sucrose feeding, there was no significant difference in mitochondrial membrane potentials (MmPs) of isolated islets between Wistar and GK rats. MmPs were reduced by 44% in sucrose-fed GK rats but not influenced in sucrose-fed Wistar rats. Current results suggest that nutritional insults like sucrose feeding may exert deleterious effects on mitochondria, resulting in augmented beta cell loss in type 2 diabetes.

Different types of nutritional deficiencies affect different domains of spatial memory function checked in a radial arm maze

Several studies using animal models have suggested that the effects of nutritional insult on the developing brain are long-lasting and lead to permanent deficits in learning and behavior. Malnutrition can refer to the availability of all the nutrients but in insufficient quantities or it may imply that one or more of essential nutrients is either missing or is present, but in the wrong proportions in the diet. The hypothesis addressed in this study is that different domains of cognitive functioning can be affected by malnutrition and this can be related to the type of nutritional deficiency that the brain has been exposed to during development. To study the effect of nutritional deprivation during brain development, a paradigm of maternal malnutrition during the period of gestation and lactation was used and its effects were studied on the F1 offspring using Swiss albino mice. Three different types of malnutrition were used, that involve, caloric restriction, inadequate amount of protein in the diet and condition of low iron content. Our results show that the domain of spatial memory affected in the F1 generation depended on the kind of malnutrition that the mother was subjected to. Further our study shows that although hippocampal volume was reduced in all F1 pups, hippocampal subregions of the F1 animals were differentially vulnerable depending on type of malnutrition that the mother was subjected to. These results highlight the importance of qualifying the kind of malnutrition that is suffered by the mother during the period of gestation and lactation as it has consequences for the cognitive domain affected in the offspring. Awareness of this should inform prevention strategies in trying to reverse the effects of adverse maternal nutrition during critical periods in brain development.

Nutrition concerns for the patient with gastroparesis

Gastroparesis is a debilitating disease that is the consequence of a variety of conditions resulting in a significant loss of quality of life. Although many cases are mild, some patients have protracted nausea and vomiting, making it difficult, if not impossible, to maintain their hydration and nutritional status. Furthermore, therapeutic levels of medications, such as prokinetic and antiemetic agents, can be difficult to achieve. The intent of this article is to provide the clinician with suggestions to improve the nutritional status of patients with gastroparesis and offer strategies to deal with the nutritional insults that arise in these unfortunate patients.

Forensic Neuropathology and Associated Neurology

Forensic Neuropathology and Associated Neurology

Conferencia clinicopatológica de la SEMI: Coordinadores: Dres. Ramón Pujol Farriols y Miguel Aranda Sánchez Hospital General Universitario Gregorio Marañón. Madrid 4 de abril de 2006

Maternal nutrition plays a crucial role in influencing fetal growth and birth outcome. Any nutritional insult starting several weeks before pregnancy and during critical periods of gestation is known to influence fetal development and increase the risk for diseases during later life. Literature suggests that chronic adult diseases may have their origin during early life – a concept referred to as Developmental Origins of Health and Disease (DOHaD) which states that adverse exposures early in life “program” risks for later chronic disorders. Long chain polyunsaturated fatty acids (LCPUFA), mainly omega-6 and omega-3 fatty acids are known to have an effect on fetal programming. The placental supply of optimal levels of LCPUFA to the fetus during early life is extremely important for the normal growth and development of both placenta and fetus. Any alteration in placental development will result in adverse pregnancy outcome such as gestational diabetes mellitus (GDM), preeclampsia, and intrauterine growth restriction (IUGR). A disturbed materno-fetal LCPUFA supply is known to be linked with each of these pathologies. Further, a disturbed LCPUFA metabolism is reported to be associated with a number of metabolic disorders. It is likely that LCPUFA supplementation during early pregnancy may be beneficial in improving the health of the mother, improving birth outcome and thereby reducing the risk of diseases in later life.