Prenatal choline supplementation enhances metabolic outcomes with differential impact on DNA methylation in Wistar rat offspring and dams.

Choline is an essential nutrient required for proper functioning of organs and serves as a methyl donor. In liver where choline metabolism primarily occurs, glucose homeostasis is regulated through insulin receptor substrates (IRS) 1 and 2. The objective of this research was to determine the role of prenatal choline as a modulator of metabolic health and DNA methylation in liver of offspring and dams.

Understanding the role of the human gut microbiome in overweight and obesity.

The gut microbiome may be related to the prevalence of overweight and obesity, but high interindividual variability of the human microbiome complicates our understanding. Obesity often occurs concomitantly with micronutrient deficiencies that impair energy metabolism. Microbiota composition is affected by diet.

Exposure to prenatal excess or imbalanced micronutrients leads to long-term perturbations in one-carbon metabolism, trimethylamine-N-oxide and DNA methylation in Wistar rat offspring.

Prenatal multivitamins, including folic acid, are commonly consumed in excess, whereas choline, an essential nutrient and an important source of labile methyl groups, is underconsumed. Here, we characterized profiles of one-carbon metabolism and related pathways and patterns of DNA methylation in offspring exposed to excess or imbalanced micronutrients prenatally. Pregnant Wistar rats were fed either recommended 1× vitamins (RV), high 10× vitamins (HV), high 10× folic acid with recommended choline (HFolRC), or high 10× folic acid with no choline (HFolNC).

The Effect of Micronutrients on Obese Phenotype of Adult Mice Is Dependent on the Experimental Environment.

The environment of the test laboratory affects the reproducibility of treatment effects on physiological phenotypes of rodents and may be attributed to the plasticity of the epigenome due to nutrient-gene-environment interactions. Here, we explored the reproducibility of adding a multi-vitamin-mineral (MVM) mix to a nutrient-balanced high-fat (HF) diet on obesity, insulin resistance (IR), and gene expression in the tissues of adult male mice. Experiments of the same design were conducted in three independent animal facilities.

Methyl donor micronutrients, hypothalamic development and programming for metabolic disease.

Nutriture in utero is essential for fetal brain development through the regulation of neural stem cell proliferation, differentiation, and apoptosis, and has a long-lasting impact on risk of disease in offspring. This review examines the role of maternal methyl donor micronutrients in neuronal development and programming of physiological functions of the hypothalamus, with a focus on later-life metabolic outcomes. Although evidence is mainly derived from preclinical studies, recent research shows that methyl donor micronutrients (e.

Folate and Choline: Does It Take Two to Tango in Early Programming of Disease?

Background: The early life period marks a critical time during which the health trajectory of offspring can be shaped by external influences including maternal nutrition. Folate and choline are water-soluble micronutrients important for fetal development and involved in one-carbon metabolism. Intakes above and below the recommendations commonly occur for both of these nutrients including over-consumption of synthetic folic acid due to widespread vitamin supplement uses and discretionary fortification practices, whereas choline is under-consumed by a majority of the populations including pregnant women.

Micronutrients in High-Fat Diet Modify Insulin Resistance and Its Regulatory Genes in Adult Male Mice.

Scope: Obesity and insulin resistance (IR) are associated with epigenetic changes of gene expression. However, the relationship between micronutrients, epigenetic regulation of gene expression, and IR during development of diet-induced obesity has yet to be defined. Our objective is to describe the effect of micronutrient addition to diets on IR and its related genes during obesity development.

Modification of the serotonergic systems and phenotypes by gestational micronutrients.

Micronutrients consumed in excess or imbalanced amounts during pregnancy may increase the risk of metabolic diseases in offspring, but the mechanisms underlying these effects are unknown. Serotonin (5-hydroxytryptamine, 5-HT), a multifunctional indoleamine in the brain and the gut, may have key roles in regulating metabolism. We investigated the effects of gestational micronutrient intakes on the central and peripheral serotonergic systems as modulators of the offspring's metabolic phenotypes.

Effect of Choline Forms and Gut Microbiota Composition on Trimethylamine--Oxide Response in Healthy Men.

Background: Trimethylamine--oxide (TMAO), a choline-derived gut microbiota-dependent metabolite, is a newly recognized risk marker for cardiovascular disease. We sought to determine: (1) TMAO response to meals containing free versus lipid-soluble choline and (2) effects of gut microbiome on TMAO response.

Methods: In a randomized, controlled, double-blinded, crossover study, healthy men ( = 37) were provided meals containing 600 mg choline either as choline bitartrate or phosphatidylcholine, or no choline control.

Emerging Priorities for Microbiome Research.

Microbiome research has increased dramatically in recent years, driven by advances in technology and significant reductions in the cost of analysis. Such research has unlocked a wealth of data, which has yielded tremendous insight into the nature of the microbial communities, including their interactions and effects, both within a host and in an external environment as part of an ecological community. Understanding the role of microbiota, including their dynamic interactions with their hosts and other microbes, can enable the engineering of new diagnostic techniques and interventional strategies that can be used in a diverse spectrum of fields, spanning from ecology and agriculture to medicine and from forensics to exobiology.

Alpha-Amino-Beta-Carboxy-Muconate-Semialdehyde Decarboxylase Controls Dietary Niacin Requirements for NAD Synthesis.

NAD is essential for redox reactions in energy metabolism and necessary for DNA repair and epigenetic modification. Humans require sufficient amounts of dietary niacin (nicotinic acid, nicotinamide, and nicotinamide riboside) for adequate NAD synthesis. In contrast, mice easily generate sufficient NAD solely from tryptophan through the kynurenine pathway.

The metabolic fate of isotopically labeled trimethylamine-N-oxide (TMAO) in humans.

Trimethylamine-N-oxide (TMAO) is associated with chronic disease risk. However, little is known about the metabolic fate of dietary TMAO. This study sought to quantitatively elucidate the metabolic fate of orally consumed TMAO in humans.

Maternal fat-soluble vitamins, brain development, and regulation of feeding behavior: an overview of research.

Recent research shows a link between vitamin intake during pregnancy and offspring health. Inadequate intakes of water-soluble vitamins during pregnancy lead to obesity and characteristics of the metabolic syndrome, concurrent with altered developments in food intake regulatory pathways. Few studies, however, have reported on the effects of fat-soluble vitamins (A, D, E, and K) on the development of food intake regulatory pathways.

Trimethylamine-N-Oxide: Friend, Foe, or Simply Caught in the Cross-Fire?

Trimethylamine-N-oxide (TMAO), a gut-derived metabolite, has recently emerged as a candidate risk factor for cardiovascular disease and other adverse health outcomes. However, the relation between TMAO and chronic disease can be confounded by several factors, including kidney function, the gut microbiome, and flavin-containing monooxygenase 3 (FMO3) genotype. Thus, whether TMAO is a causative agent in human disease development and progression, or simply a marker of an underlying pathology, remains inconclusive.

Trimethylamine-N-oxide (TMAO) response to animal source foods varies among healthy young men and is influenced by their gut microbiota composition: A randomized controlled trial.

Scope: Trimethylamine-N-oxide (TMAO), a metabolite linked to the gut microbiota, is associated with excess risk of heart disease. We hypothesized that (i) TMAO response to animal source foods would vary among healthy men and (ii) this response would be modified by their gut microbiome.

Methods And Results: A crossover feeding trial in healthy young men (n = 40) was conducted with meals containing TMAO (fish), its dietary precursors, choline (eggs) and carnitine (beef), and a fruit control.

Role of maternal vitamins in programming health and chronic disease.

Vitamin consumption prior to and during pregnancy has increased as a result of proactive recommendations by health professionals, wide availability of vitamin supplements, and liberal food-fortification policies. Folic acid, alone or in combination with other B vitamins, is the most recommended vitamin consumed during pregnancy because deficiency of this vitamin leads to birth defects in the infant. Folic acid and other B vitamins are also integral components of biochemical processes that are essential to the development of regulatory systems that control the ability of the offspring to adapt to the external environment.

High vitamin A intake during pregnancy modifies dopaminergic reward system and decreases preference for sucrose in Wistar rat offspring.

High multivitamin (HV) content in gestational diets has long-term metabolic effects in rat offspring. These changes are associated with in utero modifications of gene expression in hypothalamic food intake regulation. However, the role of fat-soluble vitamins in mediating these effects has not been explored.

A gestational diet high in fat-soluble vitamins alters expression of genes in brain pathways and reduces sucrose preference, but not food intake, in Wistar male rat offspring.

High intakes of multivitamins (HV) during pregnancy by Wistar rats increase food intake, body weight, and characteristics of the metabolic syndrome in male offspring. In this study, high-fat soluble vitamins were fed in combination during gestation to test the hypothesis that they partially account for the effects of the HV diet. Pregnant Wistar rats (14-16/group) were fed a recommended multivitamin diet (1-fold all vitamins) or high-fat soluble vitamin diet (HFS; 10-fold vitamins A, D, E, and K) during pregnancy.

Methyl vitamins contribute to obesogenic effects of a high multivitamin gestational diet and epigenetic alterations in hypothalamic feeding pathways in Wistar rat offspring.

Scope: High multivitamin (HV, tenfold AIN-93G) gestational diets fed to Wistar rats increase food intake, obesity, and characteristics of metabolic syndrome in the offspring. We hypothesized that methyl vitamins, and specifically folate, in the HV gestational diet contribute to the obesogenic phenotypes consistent with their epigenetic effects on hypothalamic food intake regulatory mechanisms.

Methods And Results: Male offspring of dams fed the AIN-93G diet with high methyl vitamins (HMethyl; tenfold folate, vitamins B12, and B6) (Study 1) and HV with recommended folate (HVRF) (Study 2) were compared with those from HV and recommended vitamin (RV) fed dams.

A high multivitamin diet fed to Wistar rat dams during pregnancy increases maternal weight gain later in life and alters homeostatic, hedonic and peripheral regulatory systems of energy balance.

High multivitamin (10-fold, HV) and high folic acid (Fol) diets fed to pregnant Wistar rats increase body weight and characteristics of the metabolic syndrome in their offspring. Our objective was to determine the effects of a HV maternal diet on dams and whether methyl vitamins contribute to these effects. Pregnant Wistar rats were fed AIN-93G diets containing either (1) recommended multivitamins (RV, control), (2) HV, (3) HV with recommended Fol (HVRF; 1-fold Fol), or (4) RV with high methyl group vitamins (HMethyl; 10-fold Fol, vitamin B12 and B6).

Increasing vitamin A in post-weaning diets reduces food intake and body weight and modifies gene expression in brains of male rats born to dams fed a high multivitamin diet.

High multivitamin gestational diets (HV, 10-fold AIN-93G levels) increase body weight (BW) and food intake (FI) in rat offspring weaned to a recommended multivitamin (RV), but not to a HV diet. We hypothesized that high vitamin A (HA) alone, similar to HV, in post-weaning diets would prevent these effects of the HV maternal diet consistent with gene expression in FI and reward pathways. Male offspring from dams fed HV diets were weaned to a high vitamin A (HA, 10-fold AIN-93G levels), HV or RV diet for 29 weeks.

High folate gestational and post-weaning diets alter hypothalamic feeding pathways by DNA methylation in Wistar rat offspring.

Excess vitamins, especially folate, are consumed during pregnancy but later-life effects on the offspring are unknown. High multivitamin (10-fold AIN-93G, HV) gestational diets increase characteristics of metabolic syndrome in Wistar rat offspring. We hypothesized that folate, the vitamin active in DNA methylation, accounts for these effects through epigenetic modification of food intake regulatory genes.

High Folic Acid Intake during Pregnancy Lowers Body Weight and Reduces Femoral Area and Strength in Female Rat Offspring.

Rats fed gestational diets high in multivitamin or folate produce offspring of altered phenotypes. We hypothesized that female rat offspring born to dams fed a gestational diet high in folic acid (HFol) have compromised bone health and that feeding the offspring the same HFol diet attenuates these effects. Pregnant rats were fed diets with either recommended folic acid (RFol) or 10-fold higher folic acid (HFol) amounts.