• Animal models
• Gestation
• Lactation
• Maternal programming
• Metabolism
• New epigenetic factors

• Metabolic disturbances
• Metabolomics
• Newborn birthweight

• Developmental origin of health and disease
• Fetal programming
• Lean diabetes
• Maternal low protein diet
• Type 2 diabetes

• R01 DK114689 NIDDK NIH HHS
• R01 HL058144 NHLBI NIH HHS

Maternal undernutrition during pregnancy is closely associated with epigenetic changes in the child, and it affects the development of obesity throughout the child’s life. Here, we investigate the effect of fetal low protein exposure and post-weaning high-fat consumption on plasma amino acid profiles and hepatic gene expression. Mother C57BL/6J mice were fed a 20% (CN) or 9% (LP) casein diet during pregnancy. After birth, the male offspring of both these groups were fed a high-fat diet (HF) from 6 to 32 weeks. At 32 weeks, the final body weight between the two groups remained unchanged, but the LP-HF group showed markedly higher white fat weight and plasma leptin levels. The LP-HF group exhibited a significant increase in the concentrations of isoleucine, leucine, histidine, phenylalanine, serine, and tyrosine. However, no differences were observed in the lipid content in the liver. According to the hepatic gene expression analysis, the LP-HF group significantly upregulated genes involved in the chromatin modification/organization pathways. Thus, maternal low protein and a post-weaning high-fat environment contributed to severe obesity states and changes in gene expression related to hepatic chromatin modification in offspring. These findings provide novel insights for the prevention of lifestyle-related diseases at the early life stage.

Detrimental exposures in mothers are recognized as risk factors for the development of metabolic dysfunction in offspring. In contrast, maternal exercise has been reported to be an effective strategy to maintain offspring health. However, the mechanisms underlying the protective effects of maternal exercise on adult offspring metabolic homeostasis are largely unclear. This study aims to investigate whether maternal exercise before and during pregnancy could combat the adverse effects of maternal high-fat diet (HFD) on metabolism in 24-week-old male offspring and to explore the role of miRNAs in mediating the effects. Female C57BL/6 mice were fed with either control diet or HFD 3-week prior to breeding and throughout pregnancy and lactation, among whom half of the HFD-fed mice were submitted to voluntary wheel running training 3-week before and during pregnancy. Male offspring were sedentary and fed with a control diet from weaning to 24 weeks. Body weight, the content of inguinal subcutaneous adipose tissue and perirenal visceral adipose tissue, glucose tolerance, and serum insulin and lipids in offspring were analyzed. Hepatic tissues were collected for transcriptome and miRNA sequencing and reverse transcription-quantitative polymerase chain reaction validation. The results showed that maternal HFD resulted in significant glucose intolerance, insulin resistance, and dyslipidemia in adult offspring, which were negated by maternal exercise. Transcriptome sequencing showed that maternal exercise reversed perinatal HFD-regulated genes in adult offspring, which were enriched in glucose and lipid metabolic-related signaling pathways. At the same time, maternal exercise significantly rescued the changes in the expression levels of 3 hepatic miRNAs in adult offspring, and their target genes were involved in the regulation of cholesterol biosynthesis and epigenetic modification, which may play an important role in mediating the intergenerational metabolic regulation of exercise. Overall, our research pioneered the role of miRNAs in mediating the programming effects of maternal exercise on adult offspring metabolism, which might provide novel insight into the prevention and treatment of metabolic disorders in early life.

Maternal protein restriction diet (PRD) increases the risk of metabolic dysfunction in adulthood, the mechanisms during the early life of offspring are still poorly understood. Apart from genetic factors, epigenetic mechanisms are crucial to offer phenotypic plasticity in response to environmental situations and transmission. Enhancer-associated noncoding RNAs (eRNAs) transcription serves as a robust indicator of enhancer activation, and have potential roles in mediating enhancer functions and gene transcription.

Using global run-on sequencing (GRO-seq) of nascent RNA including eRNA and total RNA sequencing data, we show that early-life undernutrition causes remodeling of enhancer activity in mouse liver. Differentially expressed nascent active genes were enriched in metabolic pathways. Besides, our work detected a large number of high confidence enhancers based on eRNA transcription at the ages of 4 weeks and 7 weeks, respectively. Importantly, except for ~ 1000 remodeling enhancers, the early-life undernutrition induced instability of enhancer activity which decreased in 4 weeks and increased in adulthood. eRNA transcription mainly contributes to the regulation of some important metabolic enzymes, suggesting a link between metabolic dysfunction and enhancer transcriptional control. We discovered a novel eRNA that is positively correlated to the expression of circadian gene Cry1 with increased binding of epigenetic cofactor p300.

Our study reveals novel insights into mechanisms of metabolic dysfunction. Enhancer activity in early life acts on metabolism-associated genes, leading to the increased susceptibility of metabolic disorders.

The online version contains supplementary material available at 10.1186/s13072-021-00392-w.

• Early-life undernutrition
• Enhancer
• Global run-on sequencing
• Metabolism
• Nascent RNA

• Animal models
• DOHAD
• Development
• Fetal
• Metabolism
• Programming

• Animals
• Disease Models, Animal
• Epigenesis, Genetic
• Insulin/metabolism
• Liver/embryology
• Liver/metabolism
• Metabolism/genetics
• Rodentia
• Stress, Physiological/genetics

• MR/R022690/1 Medical Research Council
• RG93186 Medical Research Council (UK)
• RG74249 Royal Society
• RG93692 Lister Institute of Preventive Medicine

• Aging-related disease
• DNA methylation
• Developmental programming
• Epigenetics
• Intrauterine growth restriction
• Type 2 diabetes

• Aging
• Animals
• DNA Methylation
• Diabetes Mellitus, Type 2/etiology
• Diabetes Mellitus, Type 2/genetics
• Diabetes Mellitus, Type 2/physiopathology
• Epigenesis, Genetic
• Female
• Fetal Development
• Humans
• Insulin/metabolism
• Insulin Resistance
• Male

Type 2 diabetes (T2D) is commonly regarded as a disease originating from lifestyle-related factors and typically occurring after the age of 40. There is, however, consistent experimental and epidemiological data evidencing that the risk for developing T2D may largely depend on conditions early in life. In particular, intrauterine growth restriction (IUGR) induced by poor or unbalanced nutrient intake can impair fetal growth and also cause fetal adipose tissue and pancreatic β-cell dysfunction. On account of these processes, persisting adaptive changes can occur in the glucose-insulin metabolism. These changes can include reduced ability for insulin secretion and insulin resistance, and they may result in an improved capacity to store fat, thereby predisposing to the development of T2D and obesity in adulthood. Accumulating research findings indicate that epigenetic regulation of gene expression plays a critical role in linking prenatal malnutrition to the risk of later-life metabolic disorders including T2D. In animal models of IUGR, changes in both DNA methylation and expression levels of key metabolic genes were repeatedly found which persisted until adulthood. The causal link between epigenetic disturbances during development and the risk for T2D was also confirmed in several human studies. In this review, the conceptual models and empirical data are summarized and discussed regarding the contribution of epigenetic mechanisms in developmental nutritional programming of T2D.

• PPARα
• amino acid
• lipid metabolism
• maternal diet
• offspring liver
• soy protein isolate

• Adiponectin/blood
• Amino Acids/blood
• Animal Nutritional Physiological Phenomena
• Animals
• Animals, Newborn
• Blood Glucose/metabolism
• Caseins/administration & dosage
• Cholesterol/blood
• Dietary Supplements
• Fatty Acids, Nonesterified/blood
• Female
• Genistein/administration & dosage
• Homocysteine/blood
• Insulin/blood
• Isoflavones/administration & dosage
• Lipid Metabolism/drug effects
• Liver/drug effects
• Liver/metabolism
• Male
• Maternal Nutritional Physiological Phenomena
• PPAR alpha/genetics
• PPAR alpha/metabolism
• Pregnancy
• Rats
• Rats, Sprague-Dawley
• Soybean Proteins/administration & dosage
• Triglycerides/blood
• Triiodothyronine/blood

• Animals
• Chromium/deficiency
• DNA Methylation
• Female
• Glucose/metabolism
• Insulin/metabolism
• Liver/metabolism
• Male
• Maternal Nutritional Physiological Phenomena/genetics
• Mice
• Mice, Inbred C57BL
• Pregnancy
• Prenatal Exposure Delayed Effects/genetics
• Prenatal Exposure Delayed Effects/metabolism
• Signal Transduction
• Trace Elements/deficiency

• National Natural Science Foundation of China
• China Scholarship Council foundation
• PUMC Youth Fund
• Fundamental Research Funds for the Central Universities
• the Scientific Activities Foundation for Selected Returned Overseas Professionals of Human Resources and Social Security Ministry
• National Key Research and Development Program of China

Despite the fact that squab is consumed throughout the world because of its high nutritional value and appreciated sensory attributes, aspects related to its characterization, and in particular genetic issues, have rarely been studied. In this study, meat traits in terms of pH, water-holding capacity, intramuscular fat content, and fatty acid profile of the breast muscle of squabs from two meat pigeon breeds were determined. Breed-specific differences were detected in fat-related traits of intramuscular fat content and fatty acid composition. RNA-Sequencing was applied to compare the transcriptomes of muscle and liver tissues between squabs of two breeds to identify candidate genes associated with the differences in the capacity of fat deposition. A total of 27 differentially expressed genes assigned to pathways of lipid metabolism were identified, of which, six genes belonged to the peroxisome proliferator-activated receptor signaling pathway along with four other genes. Our results confirmed in part previous reports in livestock and provided also a number of genes which had not been related to fat deposition so far. These genes can serve as a basis for further investigations to screen markers closely associated with intramuscular fat content and fatty acid composition in squabs. The data from this study were deposited in the National Center for Biotechnology Information (NCBI)’s Sequence Read Archive under the accession numbers SRX1680021 and SRX1680022. This is the first transcriptome analysis of the muscle and liver tissue in Columba using next generation sequencing technology. Data provided here are of potential value to dissect functional genes influencing fat deposition in squabs.

• fatty acid composition
• intramuscular fat
• squab
• transcriptome

Several studies have indicated the influence of a maternal low protein diet on the fetus. However, the effect of a maternal low quality protein diet on fetal growth and development is largely unknown. Wistar rats (11 weeks old) were mated and maintained on either a chow diet with 20% casein (n = 6) as the control group (C), or a low quality protein diet with 20% wheat gluten (n = 7) as the experimental group (WG) through gestation and lactation. Maternal body weights were similar in both groups throughout the study. Birth weights were not influenced by maternal diet and offspring body weights during lactation were similar between the groups. Offspring’s plasma amino acid profiles showed that plasma methionine, glutamine and lysine were significantly lower and aspartic acid, ornithine and glycine-proline were significantly higher in the WG. Plant based protein comprises an important part of protein intake in developing countries. It is well-known that these diets can be inadequate in terms of essential amino acids. The current study shows differential effects of a maternal low quality protein diet on the offspring’s plasma amino acids. Future studies will examine further aspects of the influence of maternal low quality protein diets on fetal growth and development.

• fetal programming
• low quality protein
• pregnancy
• rats

• Amino Acids/blood
• Animal Nutritional Physiological Phenomena
• Animals
• Diet
• Dietary Proteins/administration & dosage
• Dietary Proteins/analysis
• Female
• Maternal Nutritional Physiological Phenomena
• Pregnancy
• Rats
• Rats, Wistar
• Weaning

Liver is an important metabolic organ that plays a critical role in lipid synthesis, degradation, and transport; however, the molecular regulatory mechanisms of lipid metabolism remain unclear in chicken. In this study, RNA-Seq technology was used to investigate differences in expression profiles of hepatic lipid metabolism-related genes and associated pathways between juvenile and laying hens. The study aimed to broaden the understanding of liver lipid metabolism in chicken, and thereby to help improve laying performance in the poultry industry.

RNA-Seq analysis was carried out on total RNA harvested from the liver of juvenile (n = 3) and laying (n = 3) hens. Compared with juvenile hens, 2567 differentially expressed genes (1082 up-regulated and 1485 down-regulated) with P ≤ 0.05 were obtained in laying hens, and 960 of these genes were significantly differentially expressed (SDE) at a false discovery rate (FDR) of ≤0.05 and fold-change ≥2 or ≤0.5. In addition, most of the 198 SDE novel genes (91 up-regulated and 107 down-regulated) were discovered highly expressed, and 332 SDE isoforms were identified. Gene ontology (GO) enrichment and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis showed that the SDE genes were most enrichment in steroid biosynthesis, PPAR signaling pathway, biosynthesis of unsaturated fatty acids, glycerophospholipid metabolism, three amino acid pathways, and pyruvate metabolism (P ≤ 0.05). The top significantly enriched GO terms among the SDE genes included lipid biosynthesis, cholesterol and sterol metabolic, and oxidation reduction, indicating that principal lipogenesis occurred in the liver of laying hens.

This study suggests that the majority of changes at the transcriptome level in laying hen liver were closely related to fat metabolism. Some of the SDE uncharacterized novel genes and alternative splicing isoforms that were detected might also take part in lipid metabolism, although this needs further investigation. This study provides valuable information about the expression profiles of mRNAs from chicken liver, and in-depth functional investigations of these mRNAs could provide new insights into the molecular networks of lipid metabolism in chicken liver.

The online version of this article (doi:10.1186/s12864-015-1943-0) contains supplementary material, which is available to authorized users.