Early-life Diet Research Articles

Diet quality trajectories and cardiovascular phenotypes/metabolic syndrome risk by 11-12 years.

To investigate associations between early-life diet trajectories and preclinical cardiovascular phenotypes and metabolic risk by age 12 years. Participants were 1861 children (51% male) from the Longitudinal Study of Australian Children. At five biennial waves from 2-3 to 10-11 years: Every 2 years from 2006 to 2014, diet quality scores were collected from brief 24-h parent/self-reported dietary recalls and then classified using group-based trajectory modeling as 'never healthy' (7%), 'becoming less healthy' (17%), 'moderately healthy' (21%), and 'always healthy' (56%). At 11-12 years: During children's physical health Child Health CheckPoint (2015-2016), we measured cardiovascular functional (resting heart rate, blood pressure, pulse wave velocity, carotid elasticity/distensibility) and structural (carotid intima-media thickness, retinal microvasculature) phenotypes, and metabolic risk score (composite of body mass index z-score, systolic blood pressure, high-density lipoproteins cholesterol, triglycerides, and glucose). Associations were estimated using linear regression models (n = 1100-1800) adjusted for age, sex, and socioeconomic position. Compared to 'always healthy', the 'never healthy' trajectory had higher resting heart rate (2.6 bpm, 95% CI 0.4, 4.7) and metabolic risk score (0.23, 95% CI 0.01, 0.45), and lower arterial elasticity (-0.3% per 10 mmHg, 95% CI -0.6, -0.1) and distensibility (-1.2%, 95% CI -1.9, -0.5) (all effect sizes 0.3-0.4). Heart rate, distensibility, and diastolic blood pressure were progressively poorer for less healthy diet trajectories (linear trends p ≤ 0.02). Effects for systolic blood pressure, pulse wave velocity, and structural phenotypes were less evident. Children following the least healthy diet trajectory had poorer functional cardiovascular phenotypes and metabolic syndrome risk, including higher resting heart rate, one of the strongest precursors of all-cause mortality. Structural phenotypes were not associated with diet trajectories, suggesting the window to prevent permanent changes remains open to at least late childhood.

Simple Sugar and Sugar-Sweetened Beverage Intake During Adolescence and Risk of Colorectal Cancer Precursors

Recent increasing trends in early-onset colorectal cancer (CRC) strongly supports that early-life diet is involved in CRC development. However, data are lacking on the relationship with high sugar intake during early life. We prospectively investigated the association of adolescent simple sugar (fructose, glucose, added sugar, total sugar) and sugar-sweetened beverage (SSB) intake with CRC precursor risk in 33,106 participants of the Nurses' Health Study II who provided adolescent dietary information in 1998 and subsequently underwent lower gastrointestinal endoscopy between 1999 and 2015. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression for clustered data. During follow-up, 2909 conventional adenomas (758 high-risk) and 2355 serrated lesions were identified (mean age at diagnoses, 52.2 ± 4.3 years). High sugar and SSB intake during adolescence was positively associated with risk of adenoma, but not serrated lesions. Per each increment of 5% of calories from total fructose intake, multivariable ORs were 1.17 (95% CI, 1.05-1.31) for total and 1.30 (95% CI, 1.06-1.60) for high-risk adenoma. By subsite, ORs were 1.12 (95% CI, 0.96-1.30) for proximal, 1.24 (95% CI, 1.05-1.47) for distal, and 1.43 (95% CI, 1.10-1.86) for rectal adenoma. Per 1 serving/day increment in SSB intake, ORs were 1.11 (95% CI, 1.02-1.20) for total and 1.30 (95% CI, 1.08-1.55) for rectal adenoma. Contrary to adolescent intake, sugar and SSB intake during adulthood was not associated with adenoma risk. High intake of simple sugars and SSBs during adolescence was associated with increased risk of conventional adenoma, especially rectal adenoma.

Microbial Regulation of Host Physiology by Short-chain Fatty Acids.

Our ancestral diet consisted of much more nondigestible fiber than that of many societies today. Thus, from an evolutionary perspective the human genome and its physiological and nutritional requirements are not well aligned to modern dietary habits. Fiber reaching the colon is anaerobically fermented by the gut bacteria, which produce short-chain fatty acids (SCFAs) as metabolic by-products. SCFAs play a role in intestinal homeostasis, helping to explain why changes in the microbiota can contribute to the pathophysiology of human diseases. Recent research has shown that SCFAs can also have effects on tissues and organs beyond the gut, through their circulation in the blood. SCFAs not only signal through binding to cognate G-protein-coupled receptors on endocrine and immune cells in the body but also induce epigenetic changes in the genome through effects on the activity of histone acetylase and histone deacetylase enzymes. Furthermore, epigenetic imprinting likely occurs in utero, highlighting the importance of the maternal diet in early life. Here we review current understanding of how SCFAs impact on human and animal physiology and discuss the potential applications of SCFAs in the prevention and treatment of human diseases.

Exposure to maternal high-fat diet induces extensive changes in the brain of adult offspring

Maternal environmental exposures, such as high-fat diets, diabetes and obesity, can induce long-term effects in offspring. These effects include increased risk of neurodevelopmental disorders (NDDs) including autism spectrum disorder (ASD), depression and anxiety. The mechanisms underlying these late-life neurologic effects are unknown. In this article, we measured changes in the offspring brain and determined which brain regions are sensitive to maternal metabolic milieu and therefore may mediate NDD risk. We showed that mice exposed to a maternal high-fat diet display extensive brain changes in adulthood despite being switched to a low-fat diet at weaning. Brain regions impacted by early-life diet include the extended amygdalar system, which plays an important role in reward-seeking behaviour. Genes preferentially expressed in these regions have functions related to feeding behaviour, while also being implicated in human NDDs, such as autism. Our data demonstrated that exposure to maternal high-fat diet in early-life leads to brain alterations that persist into adulthood, even after dietary modifications.

Effect of a Parent-Focused eHealth Intervention on Children's Fruit, Vegetable, and Discretionary Food Intake (Food4toddlers): Randomized Controlled Trial.

BackgroundIn Western countries, children’s diets are often low in fruits and vegetables and high in discretionary foods. Diet in early life tends to track through childhood and youth and even into adulthood. Interventions should, therefore, be delivered in periods when habitual traits are established, as in toddlerhood when children adapt to their family’s diet.ObjectiveIn this study, we assessed the effect of the Food4toddlers eHealth intervention, which aimed to enhance toddlers’ diets by shaping their food and eating environment.MethodsThe Food4toddlers randomized controlled trial was conducted in Norway in 2017-2018. Parent-child dyads were recruited through social media. In total, 298 parents completed an online questionnaire at baseline (mean child age 10.9 months, SD 1.2). Postintervention questionnaires were completed immediately after the intervention (ie, follow-up 1; mean child age 17.8 months, SD 1.3) and 6 months after the intervention (ie, follow-up 2; mean child age 24.2 months, SD 1.9). The intervention was guided by social cognitive theory, which targets the linked relationship between the person, the behavior, and the environment. The intervention group (148/298, 49.7%) got access to the Food4toddlers website for 6 months from baseline. The website included information on diet and on how to create a healthy food and eating environment as well as activities, recipes, and collaboration opportunities. To assess intervention effects on child diet from baseline to follow-up 1 and from baseline to follow-up 2, we used generalized estimating equations and a time × group interaction term. Between-group differences in changes over time for frequency and variety of fruits and vegetables and frequency of discretionary foods were assessed.ResultsAt follow-up 1, a significant time × group interaction was observed for the frequency of vegetable intake (P=.02). The difference between groups in the change from baseline to follow-up 1 was 0.46 vegetable items per day (95% CI 0.06-0.86) in favor of the intervention group. No other significant between-group differences in dietary changes from baseline to follow-up 1 or follow-up 2 were observed. However, there is a clear time trend showing that the intake of discretionary foods increases by time from less than 1 item per week at baseline to more than 4 items per week at 2 years of age (P<.001), regardless of group.ConclusionsA positive intervention effect was observed for the frequency of vegetable intake at follow-up 1 but not at follow-up 2. No other between-group effects on diet were observed. eHealth interventions of longer duration, including reminders after the main content of the intervention has been delivered, may be needed to obtain long-terms effects, along with tailoring in a digital or a personal form.Trial RegistrationInternational Standard Randomized Controlled Trial Number (ISRCTN) 92980420; https://doi.org/10.1186/ISRCTN92980420

Early-life effects of juvenile Western diet and exercise on adult gut microbiome composition in mice.

Alterations to the gut microbiome caused by changes in diet, consumption of antibiotics, etc., can affect host function. Moreover, perturbation of the microbiome during critical developmental periods potentially has long-lasting impacts on hosts. Using four selectively bred high runner and four non-selected control lines of mice, we examined the effects of early-life diet and exercise manipulations on the adult microbiome by sequencing the hypervariable internal transcribed spacer region of the bacterial gut community. Mice from high runner lines run ∼3-fold more on wheels than do controls, and have several other phenotypic differences (e.g. higher food consumption and body temperature) that could alter the microbiome, either acutely or in terms of coevolution. Males from generation 76 were given wheels and/or a Western diet from weaning until sexual maturity at 6 weeks of age, then housed individually without wheels on standard diet until 14 weeks of age, when fecal samples were taken. Juvenile Western diet reduced bacterial richness and diversity after the 8-week washout period (equivalent to ∼6 human years). We also found interactive effects of genetic line type, juvenile diet and/or juvenile exercise on microbiome composition and diversity. Microbial community structure clustered significantly in relation to both line type and diet. Western diet also reduced the relative abundance of Muribaculum intestinale These results constitute one of the first reports of juvenile diet having long-lasting effects on the adult microbiome after a substantial washout period. Moreover, we found interactive effects of diet with early-life exercise exposure, and a dependence of these effects on genetic background.

Microecology research: a new target for the prevention of asthma.

The incidence and prevalence of asthma have increased remarkably in recent years. There are lots of factors contributing to the occurrence and development of asthma. With the improvement of sequencing technology, it has been found that the microbiome plays an important role in the formation of asthma in early life. The roles of the microbial environment and human microbiome in the occurrence and development of asthma have attracted more and more attention. The environmental microbiome influences the occurrence of asthma by shaping the human microbiome. The specific mechanism may be related to the immune regulation of Toll-like receptors and T cells (special Tregs). Intestinal microbiome is formed and changed by regulating diet and lifestyle in early life, which may affect the development and maturation of the pulmonary immune system through the intestinal-pulmonary axis. It is well-recognized that both environmental microbiomes and human microbiomes can influence the onset of asthma. This review aims to summarize the recent advances in the research of microbiome, its relationship with asthma, and the possible mechanism of the microbiome in the occurrence and development of asthma. The research of the microbial environment and human microbiome may provide a new target for the prevention of asthma in children who have high-risk factors to allergy. However, further study of “when and how” to regulate microbiome is still needed.

Effects of an early life diet containing large phospholipid-coated lipid globules on hepatic lipid metabolism in mice

We recently reported that feeding mice in their early life a diet containing a lipid structure more similar to human milk (eIMF, Nuturis) results in lower body weights and fat mass gain upon high fat feeding in later life, compared to control (cIMF). To understand the underlying mechanisms, we now explored parameters possibly involved in this long-term effect. Male C57BL/6JOlaHsd mice, fed rodent diets containing eIMF or cIMF from postnatal (PN) day 16–42, were sacrificed at PN42. Hepatic proteins were measured using targeted proteomics. Lipids were assessed by LC–MS/MS (acylcarnitines) and GC-FID (fatty-acyl chain profiles). Early life growth and body composition, cytokines, and parameters of bile acid metabolism were similar between the groups. Hepatic concentrations of multiple proteins involved in β-oxidation (+ 17%) the TCA cycle (+ 15%) and mitochondrial antioxidative proteins (+ 28%) were significantly higher in eIMF versus cIMF-fed mice (p < 0.05). Hepatic l-carnitine levels, required for fatty acid uptake into the mitochondria, were higher (+ 33%, p < 0.01) in eIMF-fed mice. The present study indicates that eIMF-fed mice have higher hepatic levels of proteins involved in fatty acid metabolism and oxidation. We speculate that eIMF feeding programs the metabolic handling of dietary lipids.

Adolescent dairy product and calcium intake in relation to later prostate cancer risk and mortality in the NIH-AARP Diet and Health Study.

Although a growing body of evidence supports an early-life contribution to prostate cancer (PCa) development, few studies have investigated early-life diet, and only three have examined early-life dairy product intake, a promising candidate risk factor because of its known/suspected influence on insulin-like growth factor levels and height. We used recalled dietary data from 162,816 participants in the NIH-AARP Diet and Health Study to investigate associations for milk, cheese, ice cream, total dairy, and calcium intake at ages 12-13years with incident total (n = 17,729), advanced (n = 2,348), and fatal PCa (n = 827) over 14years of follow-up. We calculated relative risks (RRs) and 95% confidence intervals (CIs) by Cox proportional hazards regression. We observed suggestive positive trends for milk, dairy, and calcium intake with total and/or advanced PCa (p-trends = 0.016-0.148). These trends attenuated after adjustment for additional components of adolescent diet, particularly red meat and vegetables/potatoes. In contrast, suggestive inverse trends were observed for cheese and ice cream intake with total and/or advanced PCa (p-trends = 0.043-0.153), and for milk, dairy, and calcium intake with fatal PCa (p-trend = 0.045-0.117). Although these findings provide some support for a role of adolescent diet in increasing PCa risk, particularly for correlates of milk intake or overall dietary patterns, our protective findings for cheese and ice cream intake with PCa risk and mortality, and for all dairy products with PCa mortality, suggest alternative explanations, such as the influence of early-life socioeconomic status, and increased PCa screening, earlier detection, and better PCa care.

The influence of developmental diet on reproduction and metabolism in Drosophila

BackgroundThe adaptive significance of phenotypic changes elicited by environmental conditions experienced early in life has long attracted attention in evolutionary biology. In this study, we used Drosophila melanogaster to test whether the developmental diet produces phenotypes better adapted to cope with similar nutritional conditions later in life. To discriminate among competing hypotheses on the underlying nature of developmental plasticity, we employed a full factorial design with several developmental and adult diets. Specifically, we examined the effects of early- and late-life diets (by varying their yeast and sugar contents) on reproductive fitness and on the amount of energy reserves (fat and glycogen) in two wild-caught populations.ResultsWe found that individuals that had developed on either low-yeast or high-sugar diet showed decreased reproductive performance regardless of their adult nutritional environment. The lower reproductive fitness might be caused by smaller body size and reduced ovariole number. Overall, these results are consistent with the silver spoon concept, which posits that development in a suboptimal environment negatively affects fitness-associated traits. On the other hand, the higher amount of energy reserves (fat) in individuals that had developed in a suboptimal environment might represent either an adaptive response or a side-effect of compensatory feeding.ConclusionOur findings suggest that the observed differences in the adult physiology induced by early-life diet likely result from inevitable and general effects of nutrition on the development of reproductive and metabolic organs, rather than from adaptive mechanisms.

An early-life diet containing large phospholipid-coated lipid globules programmes later-life postabsorptive lipid trafficking in high-fat diet- but not in low-fat diet-fed mice.

Feeding mice in early life a diet containing an experimental infant milk formula (Nuturis®; eIMF), with a lipid structure similar to human milk, transiently lowered body weight (BW) and fat mass gain upon Western-style diet later in life, when compared with mice fed diets based on control IMF (cIMF). We tested the hypothesis that early-life eIMF feeding alters the absorption or the postabsorptive trafficking of dietary lipids in later life. Male C57BL/6JOlaHsd mice were fed eIMF/cIMF from postnatal day 16-42, followed by low- (LFD, American Institute of Nutrition (AIN)-93 G, 7 wt% fat) or high-fat diet (HFD, D12451, 24 wt% fat) until day 63-70. Lipid absorption rate and tissue concentrations were determined after intragastric administration of stable isotope (2H or 13C) labelled lipids in separate groups. Lipid enrichments in plasma and tissues were analysed using GC-MS. The rate of triolein absorption was similar between eIMF and cIMF fed LFD: 3·2 (sd 1·8) and 3·9 (sd 2·1) and HFD: 2·6 (sd 1·7) and 3·8 (sd 3·0) % dose/ml per h. Postabsorptive lipid trafficking, that is, concentrations of absorbed lipids in tissues, was similar in the eIMF and cIMF groups after LFD. Tissue levels of absorbed TAG after HFD feeding were lower in heart (-42 %) and liver (-46 %), and higher in muscle (+81 %, all P < 0·05) in eIMF-fed mice. In conclusion, early-life IMF diet affected postabsorptive trafficking of absorbed lipids after HFD, but not LFD. Changes in postabsorptive lipid trafficking could underlie the observed lower BW and body fat accumulation in later life upon a persistent long-term obesogenic challenge.

Adjusting the Prerelease Gut Microbial Community by Diet Training to Improve the Postrelease Fitness of Captive-Bred Acipenser dabryanus.

As one of the most important tool for biodiversity restoration and endangered species conservation, reintroduction has been implemented worldwide. In reintroduction projects, prerelease conditioning could effectively increase postrelease fitness and survival by improving animals’ adaptation to transformation from artificial to natural environments. However, how early-life diet training affects individuals’ adaptation, fitness, and survival after release remains largely unknown. We hypothesized that early-life diet training would adjust the host’s gut microbial community, the gut microbial community would influence the host’s diet preference, and the host’s diet preference would impact its adaptation to diet provision transformation and then determine postrelease fitness and survival. To verify this hypothesis, we investigated the growth characteristics and gut microbes of Yangtze sturgeon (Acipenser dabryanus) trained with natural and formula diets at both the prerelease and postrelease stages. The results showed that (1) the gut microbial communities of the individuals trained with a natural diet (i.e., natural diet group) and formula diet (i.e., formula diet group) evolved to the optimal status for their corresponding diet provisions, (2) the individuals in the natural diet group paid a lower cost (i.e., changed their gut microbial communities less) during diet transformation and release into the natural environment than did the individuals in the formula diet group, and (3) the gut microbes in the natural diet group better supported postrelease fitness and survival than did the gut microbes in the formula diet group. The results indicated that better prerelease diet training with more appropriate training diets and times could improve the reintroduction of Yangtze sturgeon by adjusting the prerelease gut microbial community. Because a relationship between diet (preference) and gut microbes is common in animals from insects (such as Drosophila melanogaster) to mammals (such as Homo sapiens), our hypothesis verified by the case study on Yangtze sturgeon applies to other animals. We therefore encourage future studies to identify optimal training diets and times for each species to best adjust its prerelease gut microbial community and then improve its postrelease fitness and survival in reintroduction projects.

Understanding the Elements of Maternal Protection from Systemic Bacterial Infections during Early Life.

Late-onset sepsis (LOS) and other systemic bloodstream infections are notable causes of neonatal mortality, particularly in prematurely born very low birth weight infants. Breastfeeding in early life has numerous health benefits, impacting the health of the newborn in both the short-term and in the long-term. Though the known benefits of an exclusive mother’s own milk diet in early life have been well recognized and described, it is less understood how breastfed infants enjoy a potential reduction in risk of LOS and other systemic infections. Here we review how gut residing pathogens within the intestinal microbiota of infants can cause a subset of sepsis cases and the components of breastmilk that may prevent the dissemination of pathogens from the intestine.

Reconstructing Breastmilk and Infant Formula Intake using Novel Biomarkers in Baby Teeth

TPS 911: Air pollution, epigenetics, biomarkers, Exhibition Hall, Ground floor, August 26, 2019, 3:00 PM - 4:30 PM Background/Aim: Early life diet is a major determinant of lifelong health trajectories. However, studies of the long term health outcomes of breastfeeding are difficult to study due to cost and time restraints in collecting data prospectively and the inherent limitations of questionnaires. A biomarker that can retrospectively measure the dose and duration of breastmilk and formula feeding would be a major advancement in the study of health trajectories associated with infant diet, particularly for health outcomes measured much later in life, years after the cessation of breastfeeding. We show that chemical signals in baby teeth can reconstruct breastfeeding histories. Methods: We measure chemical signatures in aged dentine layers to generate weekly estimates of biomarkers of infant diet. Using reversed distributed lag models (DLM) we identified chemical signatures in teeth associated with breastmilk or formula intake and developed an index of breastmilk intake using a lagged weighted quantile sum (WQS) regression approach. Biomarkers of milk intake were developed in a non-human primate model and refined in a human cohort. We tested the index against prospectively collected breastfeeding histories in a human cohort based in Mexico (n=225) and a replication cohort from the US (n=100). Results: Preliminary studies identified barium as a sensitive marker of infant diet transition from breastmilk to infant formula, identifying the timing of infant formula introduction in 70% of teeth. Reversed DLMs indicated strontium as a sensitive marker to infant formula intake and lithium as a marker for breastfeeding after 6 months. Using WQS, lithium and strontium were found to be the strongest contributors within a mixture to differentiate breastfed and formula fed infants. Conclusions: Breastmilk intake during childhood can be reconstructed using chemical signatures in teeth. This method can be applied to more accurately investigate associations of breastfeeding dose and duration with long term health outcomes.

Maternal Low-Fat Diet Programs the Hepatic Epigenome despite Exposure to an Obesogenic Postnatal Diet.

Obesity and metabolic disease present a danger to long-term health outcomes. It has been hypothesized that epigenetic marks established during early life might program individuals and have either beneficial or harmful consequences later in life. In the present study, we examined whether maternal diet alters DNA methylation and whether such modifications persist after an obesogenic postnatal dietary challenge. During gestation and lactation, male Sprague-Dawley rats were exposed to either a high-fat diet (HF; n = 10) or low-fat diet (LF; n = 10). After weaning, all animals were fed a HF diet for an additional nine weeks. There were no differences observed in food intake or body weight between groups. Hepatic DNA methylation was quantified using both methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylation-sensitive restriction enzyme sequencing (MRE-seq). Overall, 1419 differentially methylated regions (DMRs) were identified. DMRs tended to be located in CpG shores and were enriched for genes involved in metabolism and cancer. Gene expression was measured for 31 genes in these pathways. Map3k5 and Igf1r were confirmed to be differentially expressed. Finally, we attempted to quantify the functional relevance of intergenic DMRs. Using chromatin contact data, we saw that conserved DMRs were topologically associated with metabolism genes, which were associated with differential expression of Adh5, Enox1, and Pik3c3. We show that although maternal dietary fat is unable to reverse offspring weight gain in response to a postnatal obesogenic diet, early life diet does program the hepatic methylome. Epigenetic alterations occur primarily in metabolic and cancer pathways and are associated with altered gene expression, but it is unclear whether they bear consequence later in life.

Programming effects of an early life diet containing large phospholipid-coated lipid globules are transient under continuous exposure to a high-fat diet.

Breast-feeding is associated with a lower risk of developing obesity during childhood and adulthood compared with feeding infant milk formula (IMF). Previous studies have shown that an experimental IMF (eIMF; comprising Nuturis®) programmed mouse pups for a lower body weight and fat mass gain in adulthood when challenged with a high-fat diet (HFD) compared with a control IMF (cIMF). Nuturis has a lipid composition and structure more similar to breast milk. Here, the long-term effects were tested of a similar eIMF, but with an adapted lipid composition and a cIMF, on body weight, glucose homoeostasis, liver and adipose tissue. Nutrient composition was similar for the eIMF and cIMF; the lipid fractions comprised approximately 50 % milk fat. C57BL/6JOlaHsd mice were fed cIMF or eIMF from postnatal day (PN) 16-42 followed by an HFD until PN168. Feeding eIMF v. cIMF in early life resulted in a lower body weight (-9 %) and body fat deposition (-14 %) in adulthood (PN105). The effect appeared transient, as from PN126 onwards, after 12 weeks' HFD, eIMF-fed mice caught up on controls and body and fat weights became comparable between groups. Glucose and energy metabolism were similar between groups. At dissection (PN168), eIMF-fed mice showed larger (+27 %) epididymal fat depots and a lower (-26 %) liver weight without clear morphological aberrations. Our data suggest the size and coating but not the lipid composition of IMF fat globules underlie the programming effect observed. Prolonged exposure to an HFD challenge partly overrules the programming effect of early diet.

Effects of programming on the hepatic epigenome by maternal low‐fat diet persist in adult offspring fed an obesogenic diet

Obesity and metabolic disease present a risk to long‐term health outcomes. Epigenetic marks such as DNA methylation are established during early life and have effects on later life through developmental programming. In the present study, we examined whether maternal diet alters DNA methylation and whether such modifications persist after an obesogenic postnatal dietary challenge. During gestation and lactation, male Sprague Dawley rats were exposed to either a high‐fat diet (HF; n = 10) or low‐fat diet (LF; n = 10). After weaning, all animals were fed the HF diet until postnatal week 12. There were no differences observed in food intake or body weight between the two groups of offspring animals. Hepatic DNA methylation was quantified using both Methylated DNA Immunoprecipitation sequencing (MeDIP‐seq) and Methylation‐sensitive Restriction Enzyme sequencing (MRE‐seq). Overall, 1,419 differentially methylated regions (DMRs) were identified. DMRs tended to be located in CpG shores, as opposed to CpG islands, and were enriched for genes involved in metabolism and cancer. Gene expression was measured for 31 candidate genes in these pathways. Among these, Map3k5 and Igf1r were confirmed to be differentially expressed. When the functional relevance of intergenic DMRs was quantified using chromatin contact data, we discovered that conserved DMRs were topologically associated with metabolism genes, which was associated with differential expression of Adh5, Enox1, and Pik3c3. Overall, although maternal dietary fat was unable to reverse offspring weight gain in response to postnatal obesogenic diet, early life diet did program the hepatic methylome. Epigenetic alterations on the hepatic methylome occur primarily in metabolic and cancer pathways and are associated with altered gene expression. Physiological consequences of these epigenetic marks will require future investigations for a better understanding of epigenomic programming.Support or Funding InformationThis project was supported by UIUC Research Board grant #12192, the USDA Cooperative State Research, Education and Extension Service, Hatch project numbers # ILLU‐698‐923 and ILLU‐698‐369, ILLU‐698‐391, and the Data Purchase Program from the University of Illinois Library.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Increasing availability of ω-3 fatty acid in the early-life diet prevents the early-life stress-induced cognitive impairments without affecting metabolic alterations.

Exposure to early-life stress (ES) is associated with cognitive and metabolic deficits in adulthood. The role of early nutrition in programming these long-term effects is largely unknown. We focused on essential ω-3 and ω-6 long-chain polyunsaturated fatty acids (LCPUFA) and investigated whether ES affects central and peripheral FA profiles, as well as if and how an early diet with increased availability of ω-3 LCPUFA ( via lowering ω-6/ω-3 ratio) protects against ES-induced impairments. ES exposure [limited nesting and bedding paradigm from postnatal day (P)2 to P9] altered central and peripheral FA profiles in mice. An early diet with low ω-6/ω-3 ratio from P2 to P42 notably prevented the ES-induced cognitive impairments, and the alterations in hippocampal newborn cell survival and in CD68+ microglia, without affecting the ES-induced metabolic alterations. Other markers for hippocampal plasticity, apoptosis, and maternal care were unaffected by ES or diet. Our findings highlight the importance of early dietary lipid quality for later cognition in ES-exposed populations.-Yam, K.-Y., Schipper, L., Reemst, K., Ruigrok, S. R., Abbink, M. R., Hoeijmakers, L., Naninck, E. F. G., Zarekiani, P., Oosting, A., Van der Beek, E. M., Lucassen, P. J., Korosi, A. Increasing availability of ω-3 fatty acid in the early-life diet prevents the early-life stress-induced cognitive impairments without affecting metabolic alterations.

Effects of early nutritional stress on physiology, life histories and their trade-offs in a model ectothermic vertebrate.

Early-life experiences can have far-reaching consequences for phenotypes into adulthood. The effect of early-life experiences on fitness, particularly under adverse conditions, is mediated by resource allocation to particular life-history traits. Reptiles exhibit great variation in life histories (e.g. indeterminate growth), thus selective pressures often mitigate the effects of early-life stress, particularly on growth and maturation. We examined the effects of early-life food restriction on growth, adult body size, physiology and reproduction in the checkered garter snake. Animals were placed on one of two early-life diet treatments: normal diet (approximating ad libitum feeding) or low diet (restricted to 20% of body mass in food weekly). At 15 weeks of age, low-diet animals were switched to the normal-diet treatment. Individuals fed a restricted diet showed reduced growth rates, depressed immunocompetence and a heightened glucocorticoid response. Once food restriction was lifted, animals experiencing nutritional stress early in life (low diet) caught up with the normal-diet group by increasing their growth, and were able to recover from the negative effects of nutritional stress on immune function and physiology. Growth restriction and the subsequent allocation of resources into increasing growth rates, however, had a negative effect on fitness. Mating success was reduced in low-diet males, while low-diet females gave birth to smaller offspring. In addition, although not a direct goal of our study, we found a sex-specific effect of early-life nutritional stress on median age of survival. Our study demonstrates both immediate and long-term effects of nutritional stress on physiology and growth, reproduction, and trade-offs among them.

223 Are we raising “normal” cows? Effects of early life diet, feeding plan, and housing on the natural behavior of dairy cattle.

223 Are we raising “normal” cows? Effects of early life diet, feeding plan, and housing on the natural behavior of dairy cattle.