Nutrigenetic and Epigenetic Mechanisms of Maternal Nutrition-Induced Glucolipid Metabolism Changes in the Offspring.

Maternal nutrition during pregnancy regulates the offspring's metabolic homeostasis, including insulin sensitivity and the metabolism of glucose and lipids. The fetus undergoes a crucial period of plasticity in the uterus; metabolic changes in the fetus during pregnancy caused by maternal nutrition not only influence fetal growth and development but also have a long-term or even life-long impact for the offspring. Epigenetic modifications, such as DNA methylation, histone modification, and non-coding RNAs, play important roles in intergenerational and transgenerational effects. In this context, this narrative review comprehensively summarizes and analyzes the molecular mechanisms underlying how maternal nutrition, including a high-fat diet, polyunsaturated fatty acid diet, methyl donor nutrient supplementation, feed restriction, and protein restriction during pregnancy, impacts the genes involved in glucolipid metabolism in the liver, adipose tissue, hypothalamus, muscle, and oocytes of the offspring in terms of the epigenetic modifications. This will provide a foundation for the further exploration of nutrigenetic and epigenetic mechanisms for integrative mother-child nutrition and promotion of the offspring's health through the regulation of maternal nutrition during pregnancy. Note: This paper is part of the Nutrition Reviews Special Collection on Precision Nutrition.

Undernutrition-induced substance metabolism and energy production disorders affected the structure and function of the pituitary gland in a pregnant sheep model.

Introduction: Undernutrition spontaneously occurs in ewes during late gestation and the pituitary is an important hinge in the neurohumoral regulatory system. However, little is known about the effect of undernutrition on pituitary metabolism. Methods: Here, 10 multiparous ewes were restricted to a 30% feeding level during late gestation to establish an undernutrition model while another 10 ewes were fed normally as controls. All the ewes were sacrificed, and pituitary samples were collected to perform transcriptome, metabolome, and quantitative real-time PCR analysis and investigate the metabolic changes. Results: PCA and PLS-DA of total genes showed that undernutrition changed the total transcriptome profile of the pituitary gland, and 581 differentially expressed genes (DEGs) were identified between the two groups. Clusters of orthologous groups for eukaryotic complete genomes demonstrated that substance transport and metabolism, including lipids, carbohydrates, and amino acids, energy production and conversion, ribosomal structure and biogenesis, and the cytoskeleton were enriched by DEGs. Kyoto encyclopedia of genes and genomes pathway enrichment analysis displayed that the phagosome, intestinal immune network, and oxidative phosphorylation were enriched by DEGs. Further analysis found that undernutrition enhanced the lipid degradation and amino acid transport, repressing lipid synthesis and transport and amino acid degradation of the pituitary gland. Moreover, the general metabolic profiles and metabolic pathways were affected by undernutrition, repressing the 60S, 40S, 28S, and 39S subunits of the ribosomal structure for translation and myosin and actin synthesis for cytoskeleton. Undernutrition was found also to be implicated in the suppression of oxidative phosphorylation for energy production and conversion into a downregulation of genes related to T cell function and the immune response and an upregulation of genes involved in inflammatory reactions enriching phagosomes. Discussion: This study comprehensively analyses the effect of undernutrition on the pituitary gland in a pregnant sheep model, which provides a foundation for further research into the mechanisms of undernutrition-caused hormone secretion and metabolic disorders.

Effects of Diets Containing Different Levels of Copper, Manganese, and Iodine on Rumen Fermentation, Blood Parameters, and Growth Performance of Yaks.

Copper, manganese, and iodine are part of a yak's required trace elements. However, knowledge about their dietary requirements is scarce. Therefore, an experiment was conducted to evaluate rumen fermentation, blood parameters, and growth performance and screen out the optimum levels of trace elements in yaks' diet. Here, 18 three-year-old castrated yaks were randomly divided into four groups, which fed with diets containing basal (CON: 4.40, 33.82, and 0 mg/kg) and low-level (LL: 10.00, 40.00, and 0.30 mg/kg), middle-level (ML: 15.00, 50.00, and 0.50 mg/kg), and high-level (HL: 20.00, 60.00, and 0.70 mg/kg) copper, manganese, and iodine for 30 days. With the increase in trace elements, yaks' daily weight gain (DWG), rumen pH, ammonia nitrogen, microbial protein (MCP), and volatile fatty acids levels and serum triglycerides and urea nitrogen levels showed firstly increasing and then decreasing trends and reached the highest values in ML, and serum ceruloplasmin and total superoxide dismutase (T-SOD) activities showed continuously increasing trends. Yaks' DWG, rumen MCP, butyrate, and valerate levels and serum triglycerides, urea nitrogen, ceruloplasmin, and T-SOD levels in ML were significantly higher than CON. Therefore, the recommended levels of copper, manganese, and iodine in growing yaks' diet are 15.00, 50.00, and 0.50 mg/kg (ML), respectively.

Effects of sources and levels of dietary supplementary manganese on growing yak's in vitro rumen fermentation.

Introduction: Manganese (Mn) is an essential trace element for livestock, but little is known about the optimal Mn source and level for yak. Methods: To improve yak's feeding standards, a 48-h in vitro study was designed to examine the effect of supplementary Mn sources including Mn sulfate (MnSO4), Mn chloride (MnCl2), and Mn methionine (Met-Mn) at five Mn levels, namely 35 mg/kg, 40 mg/kg, 50 mg/kg, 60 mg/kg, and 70 mg/kg dry matter (includes Mn in substrates), on yak's rumen fermentation. Results: Results showed that Met-Mn groups showed higher acetate (p < 0.05), propionate, total volatile fatty acids (p < 0.05) levels, ammonia nitrogen concentration (p < 0.05), dry matter digestibility (DMD), and amylase activities (p < 0.05) compared to MnSO4 and MnCl2 groups. DMD (p < 0.05), amylase activities, and trypsin activities (p < 0.05) all increased firstly and then decreased with the increase of Mn level and reached high values at 40-50 mg/kg Mn levels. Cellulase activities showed high values (p < 0.05) at 50-70 mg/kg Mn levels. Microbial protein contents (p < 0.05) and lipase activities of Mn-Met groups were higher than those of MnSO4 and MnCl2 groups at 40-50 mg/kg Mn levels. Discussion: Therefore, Mn-met was the best Mn source, and 40 to 50 mg/kg was the best Mn level for rumen fermentation of yaks.

Maternal High-Fat Diet Multigenerationally Programs HPA Function and Behaviors in Male Rat Offspring.

Maternal environmental factors have been demonstrated to exert significant influences on the health of offspring. The hypothalamic-pituitary-adrenal (HPA) axis is an important neuroendocrine stress system that can be influenced by early life challenges. Our previous research has revealed that the consumption of a high-fat diet (HFD) by pregnant and lactating rats leads to the programming of HPA axis activity in male offspring of the first generation (referred to as F1HFD/C). The present study aimed to investigate whether the observed remodeling of the HPA axis could be inherited by second-generation male offspring (referred to as F2HFD/C), following maternal HFD exposure. The results showed that F2HFD/C rats exhibited enhanced basal HPA axis activity, similar to their F1HFD/C ancestors. Moreover, F2HFD/C rats displayed exacerbated corticosterone responses to restraint and lipopolysaccharide-induced stress, but not to insulin-induced hypoglycemia stress. Furthermore, maternal HFD exposure significantly aggravated depression-like behavior in the F2 generation subjected to chronic unpredictable mild stress. To investigate the role of central calcitonin gene-related peptide (CGRP) signaling in maternal diet-induced programming of the HPA axis across generations, we conducted central infusion of αCGRP8-37, a CGRP receptor antagonist, in F2HFD/C rats. The results demonstrated that αCGRP8-37 attenuated depression-like behaviors and reduced the hyperresponsiveness of the HPA axis to restraint stress in these rats. Therefore, central CGRP signaling may contribute to maternal diet-induced programming of HPA axis across generations. In conclusion, our study provides evidence that maternal HFD consumption can lead to multigenerational programming of the HPA axis and behaviors in adult male descendants.

Undernutrition Disrupts Cecal Microbiota and Epithelium Interactions, Epithelial Metabolism, and Immune Responses in a Pregnant Sheep Model.

Undernutrition may change cecal microbiota-epithelium interactions to influence cecal feed fermentation, nutrient absorption and metabolism, and immune function. Sixteen late-gestation Hu-sheep were randomly divided into control (normal feeding) and treatment (feed restriction) groups to establish an undernourished sheep model. Cecal digesta and epithelium were collected to analyze microbiota-host interactions based on 16S rRNA gene and transcriptome sequencing. Results showed that cecal weight and pH were decreased, volatile fatty acids and microbial proteins concentrations were increased, and epithelial morphology was changed upon undernutrition. Undernutrition reduced the diversity, richness, and evenness of cecal microbiota. The relative abundances of cecal genera involved in acetate production (Rikenellaceae dgA-11 gut group, Rikenellaceae RC9 gut group, and Ruminococcus) and negatively correlated with butyrate proportion (Clostridia vadinBB60 group_norank) were decreased, while genera related to butyrate (Oscillospiraceae_uncultured and Peptococcaceae_uncultured) and valerate (Peptococcaceae_uncultured) production were increased in undernourished ewes. These findings were consistent with the decreased molar proportion of acetate and the increased molar proportions of butyrate and valerate. Undernutrition changed the overall transcriptional profile and substance transport and metabolism in cecal epithelium. Undernutrition suppressed extracellular matrix-receptor interaction and intracellular phosphatidyl inositol 3-kinase (PI3K) signaling pathway then disrupted biological processes in cecal epithelium. Moreover, undernutrition repressed phagosome antigen processing and presentation, cytokine-cytokine receptor interaction, and intestinal immune network. In conclusion, undernutrition affected cecal microbial diversity and composition and fermentation parameters, inhibited extracellular matrix-receptor interaction and the PI3K signaling pathway, and then disrupted epithelial proliferation and renewal and intestinal immune functions. Our findings exposed cecal microbiota-host interactions upon undernutrition and contribute to their further exploration. IMPORTANCE Undernutrition is commonly encountered in ruminant production, especially during pregnancy and lactation in females. Undernutrition not only induces metabolic diseases and threatens pregnant mothers' health, but also inhibits fetal growth and development, leading to weakness or even death of fetuses. Cecum works importantly in hindgut fermentation, providing volatile fatty acids and microbial proteins to the organism. Intestinal epithelial tissue plays a role in nutrient absorption and transport, barrier function, and immune function. However, little is known about cecal microbiota and epithelium interactions upon undernutrition. Our findings showed that undernutrition affected bacterial structures and functions, which changed fermentation parameters and energy regimens, and therefore affected the substance transport and metabolism in cecal epithelium. Extracellular matrix-receptor interactions were inhibited, which repressed cecal epithelial morphology and cecal weight via the PI3K signaling pathway and lowered immune response function upon undernutrition. These findings will help in further exploring microbe-host interactions.