scholarly journals [6S]-5-Methyltetrahydrofolic Acid and Folic Acid Pregnancy Diets Differentially Program Metabolic Phenotype and Hypothalamic Gene Expression of Wistar Rat Dams Post-Birth

Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 48
Author(s):  
Emanuela Pannia ◽  
Rola Hammoud ◽  
Rebecca Simonian ◽  
Erland Arning ◽  
Paula Ashcraft ◽  
...  
Keyword(s):  
Gene Expression ◽  
Folic Acid ◽  
Food Intake ◽  
Rna Sequencing ◽  
Control Diet ◽  
Wistar Rat ◽  
Metabolic Phenotype ◽  
Maternal Metabolism ◽  
Plasma Hormones ◽  
Plasma Leptin

[6S]-5-methyltetrahydrofolic acid (MTHF) is a proposed replacement for folic acid (FA) in diets and prenatal supplements. This study compared the effects of these two forms on maternal metabolism and hypothalamic gene expression. Pregnant Wistar rats received an AIN-93G diet with recommended FA (1X, 2 mg/kg, control), 5X-FA or equimolar levels of MTHF. During lactation they received the control diet and then a high fat diet for 19-weeks post-weaning. Body weight, adiposity, food intake, energy expenditure, plasma hormones, folate, and 1-carbon metabolites were measured. RNA-sequencing of the hypothalamus was conducted at parturition. Weight-loss from weaning to 1-week post-weaning was less in dams fed either form of the 5X vs. 1X folate diets, but final weight-gain was higher in 5X-MTHF vs. 5X-FA dams. Both doses of the MTHF diets led to 8% higher food intake and associated with lower plasma leptin at parturition, but higher leptin at 19-weeks and insulin resistance at 1-week post-weaning. RNA-sequencing revealed 279 differentially expressed genes in the hypothalamus in 5X-MTHF vs. 5X-FA dams. These findings indicate that MTHF and FA differ in their programing effects on maternal phenotype, and a potential adverse role of either form when given at the higher doses.

scholarly journals Dietary Intakes of Folic Acid During Pregnancy Determines Maternal Re-Set of Metabolism Post-Birth in Wistar Rat Dams (FS08-06-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Emanuela Pannia ◽  
Neil Yang ◽  
Mandy Ho ◽  
Rola Hammoud ◽  
Ruslan Kubant ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Folic Acid ◽  
Food Intake ◽  
Metabolic Pathways ◽  
Wistar Rat ◽  
Metabolic Effects ◽  
Metabolic Phenotype ◽  
Maternal Metabolism ◽  
Carbon Pathways

Abstract Objectives Nutrition during pregnancy alters the “re-set” of maternal metabolism and in turn the mother's metabolic phenotype later in life. Folic acid (FA, synthetic folate) consumed at intakes above requirements during pregnancy by rats leads to increased weight gain and altered DNA methylation in central and peripheral pathways regulating food intake. The objectives of this study were to examine the effects of intakes below and above FA dietary requirements on the re-set of energy metabolic pathways in Wistar rat mothers early post-birth. Methods Pregnant Wistar rats (n = 12/group) were fed an AIN93G diet with 5 levels of FA: 0X, 1X (control, 2 mg FA/kg), 2.5X, 5X or 10X. Dams were fed 1X-FA during lactation up to 1-week post-weaning (PW) when maternal metabolism is thought to re-set to homeostasis and then terminated. Weekly body weight, food intake, expression of hypothalamic food-intake neurons, mRNA and protein expression of folate-related and energy metabolic genes, and glucoregulatory hormones were measured. The homeostatic model assessment of insulin resistance (HOMA-IR) was used as a surrogate index of insulin resistance. Results Below (0X) and above (5X and 10X) FA requirements during pregnancy suppressed expression of hepatic folate metabolism (methyltetrahydrofolate (MTHF) reductase, and methionine synthase; P < 0.05) genes and led to higher 5-MTHF (P < 0.005) in blood compared to control suggesting dysregulation of 1-carbon pathways. Dams fed 0X- and 5X-FA also had higher plasma insulin and HOMA-IR than controls and changes in glucose and lipid metabolism-regulating genes in muscle (Glucose transporter-4, and Peroxisome-proliferator activated receptors; P < 0.05) but not liver or adipose at 1-week PW. The diets did not affect expression of hypothalamic food intake neurons nor body weight or food intake of the dams from birth to 1-week PW. Conclusions FA below (0X) or above (5X, 10X) requirements during pregnancy induce dysregulation of 1-carbon pathways and delay re-set of energy metabolic pathways in Wistar rat dams by 4-weeks after birth, potentially programming long-term negative metabolic effects. Funding Sources This research was supported by: Canadian Institute of Health Research, Institute of Nutrition, Metabolism and Diabetes (CIHR-INMD); EP supported by NSERC Alexander Graham Bell Canada Graduate Scholarships-Doctoral Program (CGS D).

scholarly journals Choline and Folic Acid Balance in Diets During Pregnancy Programs Food Intake Regulation in Wistar Rat Offspring (FS08-05-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Rola Hammoud ◽  
Chih-Sheng Liao ◽  
Emanuela Pannia ◽  
Mandy Ho ◽  
Neil Yang ◽  
...  
Keyword(s):  
Body Weight ◽  
Folic Acid ◽  
Weight Gain ◽  
Food Intake ◽  
Body Weight Gain ◽  
Control Diet ◽  
Wistar Rat ◽  
Rat Offspring ◽  
Food Intake Regulation ◽  
Intake Regulation

Abstract Objectives High gestational folic acid (FA) induces an obesogenic phenotype in male Wistar rat offspring. Imbalances between FA and other methyl-nutrients (i.e., choline) leading to perturbations in the 1-carbon cycle may account for the effects of high FA diets. Canadian women consume high (2–7-fold) intakes of FA, but most are not meeting recommended adequate intakes for choline. Choline is also absent from Canadian prenatal supplements. The objective of this study is to evaluate the effects of the interaction between choline and FA in maternal diets of rats on the 1-carbon cycle, and the programming of food intake, body weight gain and biomarkers of obesity in the offspring later in life. Methods Pregnant Wistar rat dams were fed the AIN-93 G diet with recommended (1X) choline and FA (RCRF, control), or a 5X FA diet with either 0.5X choline (LCHF), 1X choline (RCHF), or 2.5X choline (HCHF). Brain and blood were collected at birth. At weaning one male pup/dam from all groups was maintained on the control diet for 20 weeks then terminated. Dependent measures include weekly body weight-gain and food intake, plasma glucoregulatory hormones and 1-carbon metabolites at birth and post-weaning. Results Increasing choline content to 2.5-fold in a high (5-fold) gestational FA diet (HCHF) led to lower plasma insulin and leptin levels at birth compared to the LCHF and RCHF diets, respectively (P < 0.05). It also led to lower (25%, P = 0.03) plasma 5-methyltetrahydrofolate concentrations at birth compared to the RCHF diet, suggesting more efficient utilization of FA. Offspring born to dams maintained on a high folic acid diet with either low or recommended choline had higher weekly food intake (6%, P < 0.05) and body weight-gain (9%, P < 0.01). In contrast, offspring from dams fed the HCHF gestational diet were not different from those born to dams fed the RCRF (control) diet, highlighting the mitigating effects of a balanced choline and FA gestational diet. Conclusions Increased intakes of choline mitigate the effects of high FA diets. Maternal dietary choline interacts with FA on the long-term programming of food intake regulation in the offspring; emphasizing a need for more attention to improving choline intakes by women of child-bearing age. Funding Sources This research was funded by the Canadian Institute of Health Research, Institute of Nutrition, Metabolism and Diabetes (CIHR-INMD).

scholarly journals High Levels of Prebiotic Resistant Starch in Diet Modulate Gene Expression and Metabolomic Profile in Pancreatic Cancer Xenograft Mice

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 709 ◽  
Author(s):  
Concetta Panebianco ◽  
Annacandida Villani ◽  
Valerio Pazienza
Keyword(s):  
Gene Expression ◽  
Pancreatic Cancer ◽  
Resistant Starch ◽  
Control Diet ◽  
Metabolic Phenotype ◽  
Cancer Drug ◽  
Nutritional Interventions ◽  
Cancer Drug Resistance ◽  
Xenograft Mice ◽  
The Impact

Cancer initiation and protection mainly derives from a systemic metabolic environment regulated by dietary patterns. Less is known about the impact of nutritional interventions in people with a diagnosis of cancer. The aim of our study was to investigate the effect of a diet rich in resistant starch (RS) on cell pathways modulation and metabolomic phenotype in pancreatic cancer xenograft mice. RNA-Seq experiments on tumor tissue showed that 25 genes resulted in dysregulated pancreatic cancer in mice fed with an RS diet, as compared to those fed with control diet. Moreover, in these two different mice groups, six serum metabolites were deregulated as detected by LC–MS analysis. A bioinformatic prediction analysis showed the involvement of the differentially expressed genes on insulin receptor signaling, circadian rhythm signaling, and cancer drug resistance among the three top canonical pathways, whilst cell death and survival, gene expression, and neurological disease were among the three top disease and biological functions. These findings shed light on the genomic and metabolic phenotype, contributing to the knowledge of the mechanisms through which RS may act as a potential supportive approach for enhancing the efficacy of existing cancer treatments.

Gestational folic acid content alters the development and function of hypothalamic food intake regulating neurons in Wistar rat offspring post-weaning

2018 ◽  
Vol 23 (2) ◽  
pp. 149-160 ◽  
Author(s):  
Neil Victor Yang ◽  
Emanuela Pannia ◽  
Diptendu Chatterjee ◽  
Ruslan Kubant ◽  
Mandy Ho ◽  
...  
Keyword(s):  
Folic Acid ◽  
Food Intake ◽  
Acid Content ◽  
Wistar Rat ◽  
Rat Offspring ◽  
And Function

Dietary fish oil positively regulates plasma leptin and adiponectin levels in sucrose-fed, insulin-resistant rats

2005 ◽  
Vol 289 (2) ◽  
pp. R486-R494 ◽  
Author(s):  
Andrea S. Rossi ◽  
Yolanda B. Lombardo ◽  
Jean-Marc Lacorte ◽  
Adriana G. Chicco ◽  
Christine Rouault ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Fish Oil ◽  
Essential Role ◽  
Control Diet ◽  
Insulin Resistant ◽  
Dietary Fish ◽  
Plasma Leptin

Insulin resistance and adiposity induced by a long-term sucrose-rich diet (SRD) in rats could be reversed by fish oil (FO). Regulation of plasma leptin and adiponectin levels, as well as their gene expression, by FO might be implicated in these findings. This study was designed to evaluate the long-term regulation of leptin and adiponectin by dietary FO in a dietary model of insulin resistance induced by long-term SRD in rats and to determine their impact on adiposity and insulin sensitivity. Rats were randomized to consume a control diet (CD; n = 25) or an SRD ( n = 50) for 7 mo. Subsequently, the SRD-fed rats were randomized to consume SRD+FO or to continue on SRD for an additional 2 mo. Long-term SRD induced overweight and decreased both plasma leptin and adiponectin levels without change in gene expression. Dyslipidemia, adiposity, and insulin resistance accompanied these modifications. Shifting the source of fat to FO for 2 mo increased plasma levels of both adipokines, reversed insulin resistance and dyslipidemia, and improved adiposity. These results were not associated with modifications in gene expression. These results suggest that increasing both adipokines by dietary FO might play an essential role in the normalization of insulin resistance and adiposity in dietary-induced, insulin-resistant models.

scholarly journals High 5MTHF, but Not Folic Acid During Pregnancy, Alters Hypothalamic Regulatory Pathways and Associates with Post-Partum Weight-Gain in Wistar Rat Mothers

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1230-1230
Author(s):  
Emanuela Pannia ◽  
Rola Hammoud ◽  
Ruslan Kubant ◽  
Rebecca Simonian ◽  
Zdenka Pausova ◽  
...  
Keyword(s):  
Body Weight ◽  
Folic Acid ◽  
Weight Gain ◽  
Food Intake ◽  
Differentially Expressed Genes ◽  
Hormone Receptor ◽  
Body Weight Gain ◽  
Post Partum ◽  
Wistar Rat ◽  
Regulatory Pathways

Abstract Objectives 5-methyltetrahydrofolate (5MTHF), the bioactive folate form, has been proposed an alternative supplement to folic acid (FA) due to direct cellular uptake and utilization. In North America, 5MTHF is incorporated into prenatal supplements at the equivalent high dose (1000 µg) as FA and discussion has been raised of its formation into baby formula. Our lab was the first to compare the dose (1X vs high, 5X) and form (FA vs 5MTHF) effects of folate during pregnancy on later-life metabolic health of the Wistar rat mother. Contrary to our hypothesis, 5MTHF diets, independent of dose, led to mothers with 40% greater body weight-gain and higher food intake post-birth compared to FA. The objective of this study was to identify differentially expressed genes and related hypothalamic pathways of mothers fed FA vs 5MTHF diets during pregnancy. Methods Pregnant Wistar rats were fed an AIN-93 G diet with recommended (1X, control, 2 mg/kg diet) or high (5X) FA or equimolar levels of 5MTHF. At birth, a subset of dams were terminated and RNA-seq analysis was performed in the arcuate nucleus of the hypothalamus (ARC), a key regulator of body weight and food intake, in dams fed the high FA and MTHF diets. Results Over 350 differentially expressed genes were identified in the ARC of dams fed high 5MTHF vs FA diets. Combining differential gene expression patterns with reported GO function terms and Kegg pathway analyses, four candidate genes (prolactin hormone receptor, corticotropin releasing hormone receptor, KISS1 peptide and dopamine receptor) were validated by qPCR thus far as plausible contributors to higher body weight-gain and food intake in 5MTHF dams. These genes correspond to neuroactive ligand-receptor interaction pathway (path: hsa04080), associated with metabolic diseases including leptin deficiency and genetic obesity. Other significantly enriched pathways included the retrograde endocannabinoid signalling and morphine addiction pathway. Conclusions High 5MTHF supplementation during pregnancy alters expression of central feeding regulatory pathways in the hypothalamus of the mother, potentially programming post-partum body-weight gain. 5MTHF, at the equivalent dose of FA, may not be the preferred folate form during pregnancy. Funding Sources CIHR-INMD; EP supported by NSERC-CGS D.

scholarly journals Folic acid in a high multivitamin diet during pregnancy increases post‐weaning weight gain and PPAR gene expression in adipose and liver of Wistar rat dams (135.2)

2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Emanuela Pannia ◽  
Clara Cho ◽  
Diana Sanchez‐Hernandez ◽  
Pedro Huot ◽  
Abraham Poon ◽  
...  
Keyword(s):  
Gene Expression ◽  
Folic Acid ◽  
Weight Gain ◽  
Wistar Rat ◽  
Weaning Weight

scholarly journals Photoperiod effects on gene expression for hypothalamic appetite-regulating peptides and food intake in the ram

2003 ◽  
Vol 284 (1) ◽  
pp. R101-R115 ◽  
Author(s):  
Iain J. Clarke ◽  
Alexandra Rao ◽  
Yves Chilliard ◽  
Carole Delavaud ◽  
Gerald A. Lincoln
Keyword(s):  
Gene Expression ◽  
Energy Balance ◽  
Food Intake ◽  
Leptin Receptor ◽  
Negative Energy ◽  
Positive Energy ◽  
Mrna Levels ◽  
Expression Of Genes ◽  
Positive Energy Balance ◽  
Plasma Leptin

Relationship between voluntary food intake (VFI) and gene expression for appetite-regulating peptides was examined in the brains of Soay rams under contrasting photoperiods. Two groups ( n = 8) were subjected to alternating block long-day (LD) and short-day photoperiods (SD) over a period of 42 wk to entrain long-term cycles in VFI. Five animals from each group were killed 18 wk into LD or SD, and the brains were collected for in situ hybridization studies. VFI was fourfold higher under LD compared with SD. Body weight, abdominal fat, or plasma leptin levels were similar under LD and SD. LD animals were in positive energy balance and sexually inactive, and SD animals were in negative energy balance and sexually active. Neuropeptide Y (NPY) mRNA levels were higher in the arcuate nucleus (ARC) under LD, and pro-opiomelanocortin expression was lower under LD. Leptin receptor (Ob-Rb) was higher in the ARC under LD. We conclude that photoperiod-induced increase in VFI correlates with expression of NPY, but not with expression of genes for other putative orexigenic peptides. Ob-Rb gene expression is regulated by photoperiod.

scholarly journals Dysregulation of Hypothalamic Gene Expression and the Oxytocinergic System by Soybean Oil Diets in Male Mice

Endocrinology ◽  
2020 ◽  
Vol 161 (2) ◽  
Author(s):  
Poonamjot Deol ◽  
Elena Kozlova ◽  
Matthew Valdez ◽  
Catherine Ho ◽  
Ei-Wen Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Soybean Oil ◽  
Messenger Rna ◽  
Control Diet ◽  
Coconut Oil ◽  
Metabolic Phenotype ◽  
Sequencing Analysis ◽  
Male Mice ◽  
Metabolic Inflammation ◽  
Obesity And Diabetes

Abstract Soybean oil consumption has increased greatly in the past half-century and is linked to obesity and diabetes. To test the hypothesis that soybean oil diet alters hypothalamic gene expression in conjunction with metabolic phenotype, we performed RNA sequencing analysis using male mice fed isocaloric, high-fat diets based on conventional soybean oil (high in linoleic acid, LA), a genetically modified, low-LA soybean oil (Plenish), and coconut oil (high in saturated fat, containing no LA). The 2 soybean oil diets had similar but nonidentical effects on the hypothalamic transcriptome, whereas the coconut oil diet had a negligible effect compared to a low-fat control diet. Dysregulated genes were associated with inflammation, neuroendocrine, neurochemical, and insulin signaling. Oxt was the only gene with metabolic, inflammation, and neurological relevance upregulated by both soybean oil diets compared to both control diets. Oxytocin immunoreactivity in the supraoptic and paraventricular nuclei of the hypothalamus was reduced, whereas plasma oxytocin and hypothalamic Oxt were increased. These central and peripheral effects of soybean oil diets were correlated with glucose intolerance but not body weight. Alterations in hypothalamic Oxt and plasma oxytocin were not observed in the coconut oil diet enriched in stigmasterol, a phytosterol found in soybean oil. We postulate that neither stigmasterol nor LA is responsible for effects of soybean oil diets on oxytocin and that Oxt messenger RNA levels could be associated with the diabetic state. Given the ubiquitous presence of soybean oil in the American diet, its observed effects on hypothalamic gene expression could have important public health ramifications.

scholarly journals High Choline During Pregnancy Reduces Characteristics of the Metabolic Syndrome in Male Wistar Rat Offspring Fed a High Fat Post-Weaning Diet

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1313-1313
Author(s):  
Rola Hammoud ◽  
Emanuela Pannia ◽  
Ruslan Kubant ◽  
Rebecca Simonian ◽  
G Harvey Anderson
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Wistar Rat ◽  
Visceral Adiposity ◽  
Metabolic Phenotype ◽  
Energy Regulation ◽  
High Fat ◽  
Rat Offspring ◽  
Postnatal Environment

Abstract Objectives The prenatal period is a critical time for fetal development, programming the offspring's later-life health in response to the postnatal environment. We have shown that a high maternal choline diet programs long-term energy regulation leading to higher food intake and weight-gain in mature rat offspring fed a normal fat diet. However, the offspring's response to an obesogenic post-weaning diet has not been described. We aim to elucidate the interaction between the choline content of the gestational diet (GD) and fat content of the post-weaning diet (PWD) on male Wistar rat offspring's long-term metabolic phenotype. Methods Pregnant Wistar rats were fed an AIN-93G diet with either recommended choline (RC, 1g/kg diet choline bitartrate) or high choline (HC, 2.5-fold). Male pups were weaned to either a normal (10%) fat (RC-NF and HC-NF) or a high (45%) fat (RC-HF and HC-HF) diet for 17 weeks. Dependent measures were body weight, food intake, visceral adiposity, plasma glucoregulatory hormones and triglycerides, and plasma and hepatic free fatty acids (FFAs). Data were analyzed with 2-way ANOVA for main effects of GD and PWD and their interaction. Measures with significant interaction effects were followed by a Student's T-test comparing groups stratified by PWD. Results HC-HF offspring had lower body weight (7%, P &lt; 0.05), and visceral adiposity (15%, P &lt; 0.05), but no difference in food intake compared to RC-HF. HC-HF offspring had lower insulin (18%, P &lt; 0.05), HOMA-IR (24%, P &lt; 0.01), and plasma triglycerides (30%, P &lt; 0.05) but no difference in leptin. Total hepatic ω-3 FFAs (30%, P &lt; 0.05) were higher and ω-6/ω-3 (P &lt; 0.01) was lower in HC-HF compared to RC-HF, indicating an ameliorated metabolic phenotype in HC-HF offspring. In contrast, HC-NF offspring had higher food intake (8%, P &lt; 0.01) and body weight (6%, P &lt; 0.05) and no difference in adiposity compared to RC-NF. They also had higher plasma leptin adjusted for adiposity (22%, P &lt; 0.05) but not insulin or HOMA-IR compared to RC-NF. Hepatic C16:1n-7/C16:0 ratio was higher in HC-NF compared to RC-NF, suggestive of dysregulated lipid metabolism. Conclusions Gestational choline supplementation is associated with improved long-term metabolic regulation in male Wistar rat offspring fed a high fat post-weaning diet. Funding Sources CIHR-Institute of Nutrition, Metabolism, and Diabetes.

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