Project description:Exposure to adverse nutritional and metabolic environments during critical periods of development can exert long-lasting effects on health outcomes of an individual and its descendants. Although such metabolic programming has been observed in multiple species and in response to distinct nutritional stressors, conclusive insights into signaling pathways and mechanisms responsible for initiating, mediating and manifesting changes to metabolism and behavior across generations remain scarce. By employing a multigenerational starvation paradigm in C. elegans, we show that starvation-induced changes in DAF-16/FoxO activity, the main downstream target of insulin/IGF-1 receptor signaling, are responsible for metabolic programming phenotypes. Tissue-specific depletion of DAF-16/FoxO during distinct developmental time points further demonstrates that DAF-16/FoxO acts in somatic tissues, but not directly in the germline, to both initiate and manifest metabolic programming. In conclusion, our study deciphers multifaceted and critical roles of highly conserved insulin/IGF-1 receptor signaling in determining health outcomes and behavior across generations.
Project description:Nutritional programming takes place in early development. Variation in the quality and/or quantity of nutrients in early development can influence long-term health and viability. However, little is known about the mechanism of nutritional programming. The live-bearing fish Xiphophorus multilineatus, has the potential to be a new model for understanding these mechanisms, given evidence of both genetic and nutritional programming influences on juvenile growth rate. To study the molecular signatures of nutritional programming, we assembled a de novo transcriptome for X. multilineatus, and used RNA-Seq to profile gene expression in the brains of males reared in low and high quality juvenile environments. We found131 genes were differentially expressed, including metabolism and appetite master regulator agrp gene.
Project description:We present a developmental transcriptome atlas of little millet. It has superior nutritional properties including high micronutrients (Fe, Zn, Ca, Mn), dietary fiber content, and low glycemic index with potential health prospective. This crop is cultivated by tribal people in the marginal areas, and it is adapted to a wide range of growing environments.
Project description:Modern lifestyle is associated with a major consumption of ultra-processed foods (UPF) due to their practicality and palatability. The ingestion of emulsifiers, a main additive in UPFs, has been related to gut inflammation, microbiota dysbiosis, adiposity and obesity. Maternal unbalanced nutritional habits during embryonic and perinatal stages perturb offspring’s long-term metabolic health, thus increasing obesity and associated comorbidity risk. However, whether maternal emulsifier consumption influences developmental programming in the offspring remains unknown. Here we show that, in mice, maternal consumption of dietary emulsifiers (1% CMC and 1% P80 in drinking water), during gestation and lactation, perturbs the development of hypothalamic energy balance regulation centers of the progeny, leads to metabolic impairments, cognition deficits and induces anxiety-like traits in a sex-specific manner. Our findings support the notion that maternal consumption of emulsifiers, common additives of UPFs, causes mild metabolic and neuropsychological malprogramming in the progeny. Our data call for nutritional advice during gestation.
Project description:We investigated the nutritional effects on gene expression in a three generation Large White pig feeding experiment. A group of experimental (E) F0 boars were fed a standard diet supplemented with high amounts of methylating micronutrients whereas a control (C) group of F0 boars received a standard diet. These differentially fed F0 boars sired F1 boars which then sired 60 F2 pigs. Gene expression profiles showed significant twofold differences in mRNA level between 8 C F2 offspring and 8 E F2 offspring for 79, 64 and 53 probes for muscle, liver and kidney RNA, respectively. We found that in liver and muscle respective pathways of lipid metabolism and metabolic pathway were over-represented for the differentially expressed genes. Gene expression in three tissue types of F2 offspring from differentially fed F0 boars were measured. F0 boars received either a standard diet or a standard diet supplemented with methylating micronutrients. These boars produced the F1 males that received exclusively the standard diet. The F2 generation was then produced with these F1 boars. Gene expression was measured in liver, skeletal muscle and kidney of 8 F2 pigs derived from F0 boars that received the standard diet and of 8 F2 pigs derived from those F0 boars that received the standard diet supplemented with methylating micronutrients.
Project description:We investigated the nutritional effects on gene expression in testes of F0 boars from a three generation Large White pig feeding experiment. A group of experimental (E) F0 boars were fed a standard diet supplemented with high amounts of methylating micronutrients whereas a control (C) group of F0 boars received a standard diet. These differentially fed F0 boars sired F1 boars which then sired 60 F2 pigs which were investigated in a previous study. The aim of this project was to investigate if the nutrition affects gene expression in testis of differentially fed boars and thus impact on spermatogenesis. We found a small number of 70 genes that were differentially expressed (fc ≥ 1) on the P<0.01 significance level. The false discovery rate (FDR) was 0.82 indicating that only a small portion of these genes are real positives. Nevertheless, we performed a pathway analysis and found this moderate differential expression associated with pathways maps of development_A2B receptor: action via G-protein alpha s, cell adhesion_Tight junctions and cell adhesion_Endothelial cell contacts by junctional mechanisms. The gene ontology (GO) processes that matched the gene expression data in boars’ testes were positive regulation of nucleobase-containing compound metabolic process, cellular response to hormone stimulus and cellular process. The pathway maps and GO processes associated with gene expression differences do not indicate a simple relationship between nutritional influences and gene expression in testes. Nevertheless the Adenosine A2B receptor influences cell differentiation and proliferation and has thus far reaching consequences. Similar applies to those GO processes positive regulation of nucleobase-containing compound metabolic process, cellular response to hormone stimulus and cellular process that were associated with differentially expressed genes between the testes samples. The expression result is thus not conclusive of whether the diet affects processes related to transmittable epigenetic marks. The results, however, indicate that the extreme supplementation of methylating micronutrients from month one to month ten of age has a very moderate (if any) effect on gene expression in boar testes as measured by microarray analysis. Gene expression in testes from differentially fed F0 boars was measured. F0 boars received either a standard diet or a standard diet supplemented with methylating micronutrients. These boars were used to study transgenerational epigenetic inheritance in a three generation pig pedigree. Therefore it was of interest if the diet affects gene expression in testes and so could impact spermatogenesis.
Project description:Maternal exposure during pregnancy is a strong determinant of offspring health outcomes. Such exposures induce changes in the offspring epigenome resulting in gene expression and functional changes. In this study, we investigated the effect of maternal Western hypercaloric diet (HCD) programming during the perinatal period and its effect on neuronal plasticity and cardiometabolic health in adult offspring. C57BL/6J dams were fed HCD for 1 month prior to mating with regular diet (RD) sires and kept on the same diet throughout pregnancy and lactation. At weaning, offspring were maintained on either HCD or RD for 3 months duration. Maternal programming resulted in male-specific hypertension and hyperglycemia, with both males and females showing increased sympathetic tone to the vasculature. Surprisingly, programmed male offspring fed on HCD exhibited lower glucose levels, less insulin resistance, and leptin levels compared to non-programmed HCD-fed male mice. Hypothalamic genes involved in glial and astrocytic differentiation were differentially methylated in programmed male offspring. Genes involved in inflammation and type 2 diabetes were targeted by differentially expressed miRNA in programmed male offspring. Methyl-seq data were supported by our findings of astrogliosis and microgliosis as well as increased microglial activation in programmed males in the paraventricular nucleus (PVN). Aligned with programming-induced protective effect in HCD male mice, we observed lower protein levels of hypothalamic TGFβ2, NF-κB2, NF-κBp65, Ser-pIRS1, and GLP1R compared to non-programmed HCD-fed male mice. In conclusion, our study shows that maternal HCD programs neuronal plasticity in the offspring and results in male-specific hypertension and hyperglycemia. On the other hand, we observed a compensatory role of programming potentially by priming metabolic pathways to handle excess nutrients in a more efficient way.