Early-life Diet Research Articles

Transgenerational programming of longevity and reproduction by post-eclosion dietary manipulation in Drosophila.

Accumulating evidence suggests that early-life diet may program one's health status by causing permanent alternations in specific organs, tissues, or metabolic or homeostatic pathways, and such programming effects may propagate across generations through heritable epigenetic modifications. However, it remains uninvestigated whether postnatal dietary changes may program longevity across generations. To address this question of important biological and public health implications, newly-born flies (F0) were collected and subjected to various post-eclosion dietary manipulations (PDMs) with different protein-carbohydrate (i.e., LP, IP or HP for low-, intermediate- or high-protein) contents or a control diet (CD). Longevity and fecundity analyses were performed with these treated F0 flies and their F1, F2 and F3 offspring, while maintained on CD at all times. The LP and HP PDMs shortened longevity, while the IP PDM extended longevity significantly up to the F3 generation. Furthermore, the LP reduced while the IP PDM increased lifetime fecundity across the F0-F2 generations. Our observations establish the first animal model for studying transgenerational inheritance of nutritional programming of longevity, making it possible to investigate the underlying epigenetic mechanisms and identify gene targets for drug discovery in future studies.

Decreased ovarian reserve, dysregulation of mitochondrial biogenesis, and increased lipid peroxidation in female mouse offspring exposed to an obesogenic maternal diet.

Maternal diet during pregnancy influences the later life reproductive potential of female offspring. We investigate the molecular mechanisms underlying the depletion of ovarian follicular reserve in young adult females following exposure to obesogenic diet in early life. Furthermore, we explore the interaction between adverse maternal diet and postweaning diet in generating reduced ovarian reserve. Female mice were exposed to either maternal obesogenic (high fat/high sugar) or maternal control diet in utero and during lactation, then weaned onto either obesogenic or control diet. At 12 wk of age, the offspring ovarian reserve was depleted following exposure to maternal obesogenic diet (P < 0.05), but not postweaning obesogenic diet. Maternal obesogenic diet was associated with increased mitochondrial DNA biogenesis (copy number P < 0.05; transcription factor A, mitochondrial expression P < 0.05), increased mitochondrial antioxidant defenses [manganese superoxide dismutase (MnSOD) P < 0.05; copper/zinc superoxide dismutase P < 0.05; glutathione peroxidase 4 P < 0.01] and increased lipoxygenase expression (arachidonate 12-lipoxygenase P < 0.05; arachidonate 15-lipoxygenase P < 0.05) in the ovary. There was also significantly increased expression of the transcriptional regulator NF-κB (P < 0.05). There was no effect of postweaning diet on any measured ovarian parameters. Maternal diet thus plays a central role in determining follicular reserve in adult female offspring. Our observations suggest that lipid peroxidation and mitochondrial biogenesis are the key intracellular pathways involved in programming of ovarian reserve.—Aiken, C. E., Tarry-Adkins, J. L., Penfold, N. C., Dearden, L., Ozanne, S. E. Decreased ovarian reserve, dysregulation of mitochondrial biogenesis, and increased lipid peroxidation in female mouse offspring exposed to an obesogenic maternal diet.

Pre-weaning dietary iron deficiency impairs spatial learning and memory in the cognitive holeboard task in piglets.

Iron deficiency is the most common nutritional deficiency in humans, affecting more than two billion people worldwide. Early-life iron deficiency can lead to irreversible deficits in learning and memory. The pig represents a promising model animal for studying such deficits, because of its similarities to humans during early development. We investigated the effects of pre-weaning dietary iron deficiency in piglets on growth, blood parameters, cognitive performance, and brain histology later in life. Four to six days after birth, 10 male sibling pairs of piglets were taken from 10 different sows. One piglet of each pair was given a 200 mg iron dextran injection and fed a control milk diet for 28 days (88 mg Fe/kg), whereas the other sibling was given a saline injection and fed an iron deficient (ID) milk diet (21 mg Fe/kg). Due to severely retarded growth of two of the ID piglets, only eight ID piglets were tested behaviorally. After dietary treatment, all piglets were fed a balanced commercial pig diet (190–240 mg Fe/kg). Starting at 7.5 weeks of age, piglets were tested in a spatial cognitive holeboard task. In this task, 4 of 16 holes contain a hidden food reward, allowing measurement of working (short-term) memory and reference (long-term) memory (RM) simultaneously. All piglets received 40–60 acquisition trials, followed by a 16-trial reversal phase. ID piglets showed permanently retarded growth and a strong decrease in blood iron parameters during dietary treatment. After treatment, ID piglets' blood iron values restored to normal levels. In the holeboard task, ID piglets showed impaired RM learning during acquisition and reversal. Iron staining at necropsy at 12 weeks of age showed that ID piglets had fewer iron-containing cells in hippocampal regions CA1 and dentate gyrus (DG). The number of iron-containing cells in CA3 correlated positively with the average RM score during acquisition across all animals. Our results support the hypothesis that early-life iron deficiency leads to lasting cognitive deficits. The piglet as a model animal, tested in the holeboard, can be useful in future research for assessing long-term cognitive effects of early-life diets or diet-induced deficiencies.

Early-life overnutrition influences spatial memory and hippocampal microgliosis

The early life nutritional environment can program hypothalamic microglial proliferation, with a predisposition to a central proinflammatory profile long-term. We hypothesise that long-term microgliosis caused by overnutrition during critical developmental periods extend beyond the hypothalamus into the hippocampus, a pivotal region in memory formation, and that this will disrupt cognition. To test this idea, we manipulated the litter sizes Wistar rat pups were suckled in, ensuring that the pups were raised in litters of 4 (neonatally overfed) or 12 (control). This model of manipulation produces long-term obesity as well as microglial priming in the hypothalamus in the neonatally overfed. Once the rats reached adulthood, we observed the effects of early life overfeeding on cognitive function using the radial arm maze to investigate rat spatial learning and memory. We also examined hippocampal microglial number and density using immunohistochemistry for ionized calcium binding protein (Iba1). Adult rats that were overfed as neonates did not consolidate spatial working and reference memory as efficiently as their control counterparts, despite reaching criterion at the same time. This was accompanied by microgliosis in the dentate gyrus of the hippocampus in the neonatally overfed. These findings suggest early-life diet may influence spatial memory formation at the level of the hippocampus.

The Ontogeny of Brown Adipose Tissue.

There are three different types of adipose tissue (AT)-brown, white, and beige-that differ with stage of development, species, and anatomical location. Of these, brown AT (BAT) is the least abundant but has the greatest potential impact on energy balance. BAT is capable of rapidly producing large amounts of heat through activation of the unique uncoupling protein 1 (UCP1) located within the inner mitochondrial membrane. White AT is an endocrine organ and site of lipid storage, whereas beige AT is primarily white but contains some cells that possess UCP1. BAT first appears in the fetus around mid-gestation and is then gradually lost through childhood, adolescence, and adulthood. We focus on the interrelationships between adipocyte classification, anatomical location, and impact of diet in early life together with the extent to which fat development differs between the major species examined. Ultimately, novel dietary interventions designed to reactivate BAT could be possible.

Nutritional Status of Pregnant Mothers Influence the Health in Adult Life of their Children

Pregnancy and fetal development are periods of rapid growth and cell differentiation when mother and offspring are vulnerable to changes. Adverse events during development can be linked to an increased risk in developing metabolic diseases. Growth restriction in utero is associated with the development of obesity, hypertension, and diabetes. In these processes, the liver plays a fundamental role. The aim of this work was to evaluate the effects of a low protein diet in pregnant and lactating mothers on the antioxidant status of the offspring liver. To reproduce real conditions, we used an experimental rat model. Both ROS and the protective antioxidant systems have to work in coordination to reach a state of redox homeostasis. Excess generation of ROS may result in cell death or different pathological processes. The study also highlights the complex nature of malnutrition injury in which ROS correlates with the hepatic injury in a cause-and-effect manner. The male offspring with intrauterine growth restriction (IUGR) caused by the isocaloric low-protein diet (8%) showed decreased liver and body weight at birth. Hepatic cholesterol levels and serum transaminase increase, at weaning (24 day of age). We observed excess generation of ROS, carbonyl group and lipoperoxidation with that may result in cell death or different pathological processes in the liver. Conclusion: This study would suggests that liver injury due to accelerated release of toxic oxygen species and impaired antioxidant status may contribute to the high susceptibility to suffer metabolic diseases, that are related to diet in early life and that manifest in adulthood.

Late gestation under- and overnutrition have differential impacts when combined with a post-natal obesogenic diet on glucose-lactate-insulin adaptations during metabolic challenges in adolescent sheep.

To determine whether late gestation under- and overnutrition programme metabolic plasticity in a similar way, and whether metabolic responses to an obesogenic diet in early post-natal life depend on the foetal nutrition history. In a 3 × 2 factorial design, twin-pregnant ewes were for the last 6 weeks of gestation (term = 147 days) assigned to HIGH (N = 13; 150 and 110% of energy and protein requirements, respectively), NORM (N = 9; 100% of requirements) or LOW (N = 14; 50% of requirements) diets. The twin offspring were raised on high-carbohydrate-high-fat (HCHF; N = 35) or conventional (CONV; N = 35) diets from 3 days to 6 months of age (around puberty). Then intravenous glucose (GTT; overnight fasted), insulin (ITT; fed) and propionate (gluconeogenetic precursor; PTT; both fed and fasted) tolerance tests were conducted to evaluate (hepatic) metabolic plasticity. Prenatal malnutrition differentially impacted adaptations of particularly plasma lactate followed by glucose, cholesterol and insulin. This was most clearly expressed during PTT in fasted lambs and much less during ITT and GTT. In fasted lambs, propionate induced more dramatic increases in lactate than glucose, and HIGH lambs became more hyperglycaemic, hyperlactataemic and secreted less insulin compared to the hypercholesterolaemic LOW lambs. Propionate-induced insulin secretion was virtually abolished in fasted HCHF lambs, but upregulated in fasted compared to fed CONV lambs. HCHF lambs had the greatest glucose-induced insulin secretory responses. Prenatal malnutrition differentially programmed glucose-lactate metabolic pathways and cholesterol homeostasis. Prenatal overnutrition predisposed for hyperglycaemia and hyperlactataemia, whereas undernutrition predisposed for hypercholesterolaemia upon exposure to an obesogenic diet. Prenatal overnutrition (not undernutrition) interfered with pancreatic insulin secretion by non-glucose-dependent mechanisms.

Abstract 4104: Obesity and colon cancer: Does time of exposure matter

Abstract Purposes: Obesity is associated with an increased risk of colon cancer in many epidemiology studies, while calorie restriction (CR) has shown protective effects on colon tumorigenesis in animal studies. This preclinical study was designed to investigate the long-term impacts of early exposure to high fat diet or CR diet on colon tumorigenesis. Methods: 50 three-week-old female C57/B6J mice were assigned into five groups: 1) control; 2) HF-control; 3) control-HF; 4) HF and 5) CR-control. Mice were initially placed on a control diet (10% kcal from fat), HF diet (45% kcal from fat), or 30% CR diet and fed ad libitum for nine weeks from the time of weaning and followed by a seven-week control diet. Azoxymethane was injected once a week for five weeks at a dose of 10 mg/kg beginning at 13 weeks of age. At 18 week-old, mice were placed on either a control diet or a HF diet. Mice were euthanized at 46 week-old and colons were collected to assess tumorigenesis. Results: After nine weeks of diet intervention, the percentage of body fat was higher in the mice on the HF diet (31.9%) and lower in those on the CR diet (18.4%), compared to mice on the control diet (20.0%, p=0.08). Mice on a CR diet in early life had lower body weights at the endpoint, compared to those on the control diet (p=0.03). Analysis of colon histopathology is ongoing as well as evaluation of apoptosis and proliferation. Conclusions: Early life exposure to calorie restriction has long-term impacts on body weight. Early life exposure to high fat diet may increase the risk of colon tumorigenesis. This model is currently being used to investigate the effects of early alterations in energy balance on colon cancer development and underlying molecular mechanisms. Citation Format: Jinyu Xu, Jennifer Thomas-Ahner, Samantha DeMarsh, Steven K. Clinton, Susan E. Olivo-Marston. Obesity and colon cancer: Does time of exposure matter. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4104. doi:10.1158/1538-7445.AM2014-4104

Early exposure of dams to a westernized diet has long-term consequences on food intake and physiometabolic homeostasis of the rat offspring

This study evaluated the long-term effects of a westernized diet during pregnancy and lactation. Female Wistar rats (n = 12) were divided into two groups according to their food intake, namely, control (C) or westernized (W) diet, throughout pregnancy/lactation. On the 21st day, the male pups were weaned on a standard diet as follows: Control diet (CC) (n = 8) and westernized diet in perinatal life followed by control diet post weaning (WC) (n = 8). The levels of fasting (12 h) serum glucose, triglycerides (TG), and total cholesterol and fraction in the pups were determined. During weaning, the WC group showed 14% greater body weight (p < 0.001). In the adulthood, the offspring from dams fed on westernized diet showed hyperphagia, hyperinsulinism, hypertriglyceridemia, higher fat visceral weight, higher very-low-density-lipoprotein cholesterol level, decreased high-density-lipoprotein cholesterol level, and altered glucose tolerance test. In conclusion, maternal western-style diet in early life altered long-term food intake, visceral fat pad, insulin, glucose and lipid serum, and increased risk of metabolic disorders.

Food intolerance and allergy: increased incidence or contemporary inadequate diets?

The role of nutrients in the study of allergic disease has been studied for many years, but recent evidence suggests that it is the quality and variety of the whole diet which affects the development of food allergy. This review seeks to understand whether food allergy prevalence is increasing and the role of diet in the development of the disease. New data on the European and global prevalence of food allergy suggest that both reported and actual rates are increasing. Recent findings from studies in infants and children indicated that a Western diet could enhance the development of allergic disease, possibly due to an effect on the homeostasis of the gut microbiome, impacting the immune status of individuals. With overall prevalence rates for food allergy increasing, it is important to ascertain the relevance of dietary influences. Attention has shifted from single-nutrient prevention studies to evaluation of the effect of different dietary patterns on allergic outcomes. Evidence suggests that introduction of complementary foods should not be delayed, and the diversity of the diet in early life is important. The increasingly processed nature of the Western diet, in combination with influences on the gut microbiome, may contribute to the rising prevalence of allergic disease, including food allergy.

Early-life nutritional programming of longevity.

Available data from both experimental and epidemiological studies suggest that inadequate diet in early life can permanently change the structure and function of specific organs or homoeostatic pathways, thereby 'programming' the individual's health status and longevity. Sufficient evidence has accumulated showing significant impact of epigenetic regulation mechanisms in nutritional programming phenomenon. The essential role of early-life diet in the development of aging-related chronic diseases is well established and described in many scientific publications. However, the programming effects on lifespan have not been extensively reviewed systematically. The aim of the review is to provide a summary of research findings and theoretical explanations that indicate that longevity can be influenced by early nutrition.

DNA methylation, ageing and the influence of early life nutrition.

It is well established that genotype plays an important role in the ageing process. However, recent studies have suggested that epigenetic mechanisms may also influence the onset of ageing-associated diseases and longevity. Epigenetics is defined as processes that induce heritable changes in gene expression without a change in the DNA nucleotide sequence. The major epigenetic mechanisms are DNA methylation, histone modification and non-coding RNA. Such processes are involved in the regulation of tissue-specific gene expression, cell differentiation and genomic imprinting. However, epigenetic dysregulation is frequently seen with ageing. Relatively little is known about the factors that initiate such changes. However, there is emerging evidence that the early life environment, in particular nutrition, in early life can induce long-term changes in DNA methylation resulting in an altered susceptibility to a range of ageing-associated diseases. In this review, we will focus on the changes in DNA methylation that occur during ageing; their role in the ageing process and how early life nutrition can modulate DNA methylation and influence longevity. Understanding the mechanisms by which diet in early life can influence the epigenome will be crucial for the development of preventative and intervention strategies to increase well-being in later life.

An exploratory randomised controlled trial of a public health nutrition intervention delivered in children's centres in Islington and Cornwall

BackgroundThe diets of preschool children are a cause for concern, with low intakes of fruit and vegetables and high intakes of sugary foods and drinks. A poor diet in early life can have a substantial effect on a child's immediate and longer term health and contributes to broader health inequalities. The aim of this study was to develop, implement, and assess a multifaceted nutrition intervention delivered in children's centres. MethodsIn line with MRC guidance for assessment of complex interventions, a mixed methods approach was used. Initially, a detailed developmental phase was undertaken with a combination of qualitative and quantitative methods to identify the nature and type of intervention needed. Detailed consideration was also given to the theoretical basis of the intervention. A multifaceted public health nutrition intervention programme was designed on the basis of the findings from the developmental phase of the study. An exploratory randomised controlled trial was done in children's centres in Islington and Cornwall to assess the newly developed intervention. 16 children's centres from both areas were randomised. Children's centres were randomly selected by the statistician from centres who expressed an interest in participating. In Cornwall, random selection was stratified by geographical location and deprivation to ensure representativeness. Participants attending intervention centres were invited to attend a 4-week nutrition programme. Staff at the intervention centres also received nutrition training and support in developing food policies. Participants attending the control centres received usual nutrition advice and support. Because of the nature of the intervention, neither the participants nor the researchers assessing the outcomes were masked to group assignment. The primary outcome was the child's daily fruit and vegetable consumption measured by weight consumed per day. Analysis was by intention to treat. A detailed process investigation was also undertaken to assess the acceptability and feasibility of the intervention and trial method. Full ethics approval was received from Camden and Islington Community Research Ethics Committee (REC 09/HO722/56). This trial is registered with ISRCTN, number CCT-NAPN-21453. Findings394 families were recruited, 199 in the intervention group and 195 in the control group. At 6-month follow-up, 77% (n=304) of families were retained in the study. Mean number of children was 1·83 (SD 0·91) with a larger family size found in Cornwall (1·96) than in Islington (1·74; p=0·04). Overall, there was a small but insignificant difference in change between the intervention and controls in mean weight of fruit and vegetables consumed (11·9 g, 95% CI −11·3 to 35·2). However, significant differences were noted in Islington in both mean weight of fruit and vegetables (39·7 g, 95% CI 1·6–77·8) and volume of sugary drinks (–65·8 mL, −131·5 to 0·0) consumed. Data from the process assessment suggested the intervention was popular with both parents and centre staff. Parents praised the practical content of the intervention programme and emphasised how it increased their self-confidence and understanding of nutrition for young children. Process assessment data also indicated that the recruitment and measurement methods were acceptable to participants. InterpretationThis study has comprehensively investigated the development, implementation, and assessment of a public health nutrition intervention in children's centres in two diverse locations, providing detailed insights valuable for planning of a definitive randomised trial. The main limitations of this exploratory trial are that it was undertaken in only two areas and the follow-up data were obtained at 6 months rather than a longer timescale. FundingCommissioned by Food Standards Agency in 2009 and supported by UK Department of Health from 2010.

Late gestation over‐ and undernutrition predispose for visceral adiposity in response to a post‐natal obesogenic diet, but with differential impacts on glucose–insulin adaptations during fasting in lambs

To investigate if late gestation under- or overnutrition has similar adverse impacts on visceral adiposity, metabolic and endocrine function in sheep, and if subsequent exposure to a high-fat diet in early post-natal life exaggerates the prenatal programming outcomes later in life. Thirty-six twin-pregnant ewes were fed a NORM (fulfilling 100% of daily requirements for energy and protein), LOW (50% of NORM) or HIGH diet (150% of energy and 110% of protein requirements) during the last 6 weeks of gestation (term = 147 days). Post-natally, the twin lambs were subjected to a high-fat or a moderate diet until 6 months of age (around puberty), where metabolic and endocrine adaptability to fasting was examined, and subgroups of animals were killed. Animals exposed to either prenatal under- or overnutrition had reduced subcutaneous fat deposition when fed a high-fat diet, resulting in higher ratios of mesenteric and peri-renal fat relative to subcutaneous fat compared to controls. This was not related to prenatal influences on plasma glucose or insulin. Irrespective of the prenatal diet, high-fat-fed lambs underwent changes resembling the metabolic syndrome with higher plasma glucose, cholesterol, non-esterified fatty acids, triglyceride and lactate combined with abdominal obesity. Peri-renal fat appeared to be a particular target of a high-fat diet post-natally. Both prenatal under- and overnutrition predisposed for abdominal adiposity, apparently by reducing the expandability of subcutaneous adipose tissue and induced differential physiological adaptations to fasting. This study does not suggest that exposure to gestational overnutrition will provide a protective effect against development of hyperglycaemia later in life.

Pre- and early-postnatal nutrition modify gene and protein expressions of muscle energy metabolism markers and phospholipid Fatty Acid composition in a muscle type specific manner in sheep.

We previously reported that undernutrition in late fetal life reduced whole-body insulin sensitivity in adult sheep, irrespective of dietary exposure in early postnatal life. Skeletal muscle may play an important role in control of insulin action. We therefore studied a range of putative key muscle determinants of insulin signalling in two types of skeletal muscles (longissimus dorsi (LD) and biceps femoris (BF)) and in the cardiac muscle (ventriculus sinister cordis (VSC)) of sheep from the same experiment. Twin-bearing ewes were fed either 100% (NORM) or 50% (LOW) of their energy and protein requirements during the last trimester of gestation. From day-3 postpartum to 6-months of age (around puberty), twin offspring received a high-carbohydrate-high-fat (HCHF) or a moderate-conventional (CONV) diet, whereafter all males were slaughtered. Females were subsequently raised on a moderate diet and slaughtered at 2-years of age (young adults). The only long-term consequences of fetal undernutrition observed in adult offspring were lower expressions of the insulin responsive glucose transporter 4 (GLUT4) protein and peroxisome proliferator-activated receptor gamma, coactivator 1α (PGC1α) mRNA in BF, but increased PGC1α expression in VSC. Interestingly, the HCHF diet in early postnatal life was associated with somewhat paradoxically increased expressions in LD of a range of genes (but not proteins) related to glucose uptake, insulin signalling and fatty acid oxidation. Except for fatty acid oxidation genes, these changes persisted into adulthood. No persistent expression changes were observed in BF and VSC. The HCHF diet increased phospholipid ratios of n-6/n-3 polyunsaturated fatty acids in all muscles, even in adults fed identical diets for 1½ years. In conclusion, early postnatal, but not late gestation, nutrition had long-term consequences for a number of determinants of insulin action and metabolism in LD. Tissues other than muscle may account for reduced whole body insulin sensitivity in adult LOW sheep.

Diet spanning infancy and toddlerhood is associated with child blood pressure at age 7.5 y

Diet in the first 2 y of life may be a pivotal period regarding effects on future blood pressure (BP). However, data on early-life diet and BP in childhood are sparse. We prospectively assessed associations between types of diet spanning infancy and toddlerhood (ie, transition diets across the complementary feeding period) and BP at age 7.5 y. In a birth cohort study (Avon Longitudinal Study of Parents and Children; United Kingdom), a total of 1229 children had complete dietary intake data at 6, 15, and 24 mo; BP data at 7.5 y of age; and all 18 covariables. Of the 2 transition diets that were extracted by using principal components analysis, the less-healthy diet was associated with an increase in systolic BP of 0.62 mm Hg (95% CI: 0.00, 1.24 mm Hg) and an increase in diastolic BP of 0.55 mm Hg (95% CI: 0.10, 1.00 mm Hg) for every one-unit (SD) increase in the less-healthy-diet score after adjustment for 15 potential confounders, including maternal characteristics and sociodemographic factors, birth variables, and breastfeeding duration. In contrast with systolic BP, the positive association between the less-healthy transition-diet score and diastolic BP persisted after additional adjustment for child body-size factors [height, body mass index (BMI), and waist circumference] at 7.5 y. A less-healthy transition diet by age 2 y was associated with higher BP at 7.5 y. The BMI-related reduction in effect size reinforces the importance of BMI on the diet-BP relation.

STABLE ISOTOPIC RECONSTRUCTION OF DIET AND RESIDENTIAL MOBILITY IN A POSTBELLUM AFRICAN AMERICAN COMMUNITY IN RURAL GEORGIA

Despite popular belief, the Great Migration following the Civil War was not a singular event but a long-term demographic phenomenon marked by freed African Americans returning to their natal communities or establishing new communities elsewhere and was presaged by smallerscale movements of African Americans between different regions of the Emancipation-era South. This study analyzes carbon and oxygen (δ13C, δ18O) stable isotope ratios in enamel carbonate from 34 individuals recovered from the Avondale Burial Place, an Emancipation-era cemetery, in Macon, Georgia, in order to reconstruct residential origin and early-life diet and examine whether these individuals immigrated to the site from elsewhere in the South. Carbon isotope results suggest mixed C3/C4 agro-pastoral subsistence rather than a reliance on C4 products such as corn and corn-fed livestock as suggested by historical accounts. Oxygen isotope results suggest that the majority of individuals buried in the Avondale Burial Place were likely born in the area as well; in comparison with other isotopic studies from postbellum contexts, these results support the interpretation that the Great Migration was a gradual process with varying impacts in different areas. Interestingly, a sex-based divergence in both carbon and oxygen isotope values during childhood suggests differences in diet and water consumption possibly related to divergent gender roles. Overall, these results indicate that despite continued hardships, the members of this community consisted of local residents, and they do not indicate the presence of migrant individuals; this isotopic analysis, therefore, contributes to a growing body of bioarchaeological research reconstructing the lost and varied histories of postbellum African American communities.

Abstract 192: Exposure to high saturated fat acid diet in early life changes the susceptibility to breast cancer in adulthood.

Abstract Nutrition is thought to be involved in 30 to 50% of all breast cancer and intake of animal fat seems to be related to the increase of this type of cancer. It has been suggested that breast cancer can originate in early life, including the in utero and lactation periods. Maternal nutrition can modify the fetal environment and induce epigenetics modifications that change the susceptibility of offspring to breast cancer in adulthood. We hypothesized that exposure to high saturated fatty acid diet (HFS) in early life can change gene expression through the remodeling of epigenetic marks and consequently modify the risk of breast cancer. Sprague-Dawley rats were used in our study, which was composed of three groups: CO (female rats exposed to control diet [AIN-93G] in utero and lactation); PG (female rats exposed to HSF in utero) and PL (female rats exposed to HSF in utero and lactation). The distribution of fatty acid in the HSF was 37%, 38% and 24% of saturated, monounsaturated and polyunsaturated, respectively while in the CO diet, the distribution of those fatty acid was 17%, 27% and 55%, respectively. Female rats were euthanized on post-natal day (PND) 50 and blood and mammary tissue collected. Serum samples were assayed for estradiol, progesterone and leptin levels (radioimmunoassay and immunofluorescence). Mammary glands were evaluated for the number of terminal End Buds (TEBs), global DNA methylation (HPLC-DAD) and global histone modification patterns (western blot). Mammary tumor development induced by oral administration of dimethylbenz[a]anthracene (DMBA) on PND50 was also evaluated. Global DNA methylation were also determined in mammary tumors. There were no differences (P&amp;gt;0.05) in maternal caloric intake, offspring birth weight, serum estradiol levels or number of TEBs among the groups. Serum progesterone levels showed a tendency to increase (P=0.07) in the PG group compared to CO group. Compared to others groups, the PL group showed higher (P≤0.05) serum leptin levels. The PG group showed higher levels (P≤0.05) of global trimethylation of histone 3 lysine 9 (H3K9me3) compared to CO group, but no differences were observed (P&amp;gt;0.05) for global DNA methylation and global H3K9/H4K16 acetylation and H3K27/H3K4 trimethylation. The PG group showed lower incidence (P≤0.05) and average number of tumors compared to CO group and higher latency (P≤0.05) compared to PL group. The tumors from PG group presented lower (P≤0.05) global DNA methylation compared to others groups. In conclusion, exposure to HSF in early life influenced the susceptibility of breast cancer in adulthood. But, differently from what we expected the exposure to this diet in utero decreased breast cancer risk. If this exposure is continued through the period of lactation the protective effect is lost. This modification of breast cancer risk in early life seems to involve epigenetics mechanisms like post-translational histone modification. Citation Format: Fábia O. Andrade, Camile C. Fontelles, Mariana Rosim, Tiago F. Oliveira, Ana PM Loureiro, Marcelo M. Rogero, Fernando S. Moreno, Sonia M. De Assis, Leena Hilakivi-Clarke, Luis F. Barbisan, Thomas P. Ong. Exposure to high saturated fat acid diet in early life changes the susceptibility to breast cancer in adulthood. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 192. doi:10.1158/1538-7445.AM2013-192

Programming of glucose–insulin homoeostasis: long‐term consequences of pre‐natal versus early post‐natal nutrition insults. Evidence from a sheep model

Exposure to adverse intra-uterine conditions can predispose for metabolic disorders later in life. By using a sheep model, we studied (i) how programming of glucose-insulin homoeostasis during late gestation is manifested later in life depending on the early post-natal dietary exposure and (ii) whether dietary alteration in obese individuals can prevent adverse outcomes of early life programming. During late gestation, twin-pregnant sheep were fed 100% (NORM) or 50% (LOW) of energy and protein requirements. After birth, offspring were exposed to a moderate (CONV) or high-carbohydrate-high-fat (HCHF) diet until around puberty. Offspring remaining thereafter (exclusively females) were fed a moderate diet until young adulthood. LOW lambs had increased insulin secretory responses during intravenous glucose tolerance tests indicative of reduced insulin sensitivity. HCHF lambs were hypertriglyceridaemic, 75% had mild pancreatic collagen infiltration, and their acute insulin secretory response and insulin clearance during intravenous glucose and insulin tolerance tests, respectively, were reduced. However, NORM-HCHF in contrast to LOW-HCHF lambs had normal glucose tolerance, indicating that later health outcomes are highly influenced by pre-natal nutrition. Dietary alteration normalized glucose-insulin homoeostasis in adult HCHF females, whereas late-gestation undernutrition (LOW) permanently depressed insulin sensitivity. Maintenance of glucose tolerance in sheep exposed to pre-natal undernutrition relied on pancreatic hypersecretion of insulin to compensate for reduced insulin sensitivity. A mismatching high-fat diet in early post-natal life interfered with this pancreatic hypersecretion resulting in reduced glucose tolerance. Early post-natal, but not late pre-natal, impacts on glucose-insulin homoeostasis could be reversed by dietary correction later in life.

Value of eggs during pregnancy and early childhood

The maternal diet is believed to influence infant health, as does diet in early life following the introduction of solid foods. Eggs, commonly available and low in cost, contain nutrients that may be of benefit during pregnancy as well as during weaning. Key nutrients include vitamin D, folate, iodine, selenium and long-chain n-3 polyunsaturated fatty acids (omega-3 fatty acids). Data from a recent nutritional analysis of eggs are presented and put in context with dietary reference values for the UK. The safety aspects of eggs, including food safety and allergy, are also discussed.