scholarly journals Choline Supplementation Mitigates the Adverse Effects of a High Folic Acid Maternal Diet on Food Intake Regulation in the Offspring

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1806-1806
Author(s):  
Rola Hammoud ◽  
Emanuela Pannia ◽  
Chih-Sheng Liao ◽  
Ruslan Kubant ◽  
Erland Arning ◽  
...  

Abstract Objectives Folic acid (FA) intake by many women in North America is exceeding recommendations. We have shown that high maternal FA induces methylation-dependent programming of energy regulation associated with an obesogenic phenotype in adult rat offspring. However, it is unclear if this is a direct effect of high FA or due to an imbalance between FA and other methyl-nutrients (i.e., choline) in the 1-carbon cycle. Unlike FA, choline intake by women is below recommendations and is absent from most prenatal supplements, potentially affecting fetal development. The objective of this study was to examine the mechanisms and effects of choline content in high FA maternal diets on in-utero programming of energy regulation and later-life offspring phenotype. Methods Pregnant Wistar rats were fed an AIN-93 G diet with recommended FA and choline (1X, RFRC, control), or 5X-FA diet with choline at 0.5X-(HFLC), 1X-(HFRC), or 2.5X- (HFHC). In pups at birth, brain and liver 1-carbon metabolites, hypothalamic DNA methyltransferase (DNMT) activity and global DNA methylation (5-mC%) were measured. At weaning, one male pup/dam was fed the control diet and weekly weight-gain and food intake were recorded for 20 weeks. Results Offspring born to dams on the HFLC and HFRC, but not HFHC diet, had higher food intake (P < 0.05) and weight-gain (P < 0.01) than controls. In liver at birth, free choline was lower in HFHC than in HFLC pups, but betaine was unaffected. In contrast, in brains, betaine but not free choline concentrations, directly reflected the maternal choline diets. These results suggest that choline may modulate central food intake pathways via the methyl-donor betaine, warranting further investigation. Hypothalamic DNMT activity was highest (P < 0.05) in HFLC pups but global methylation was not affected. Thus, gene expression by RNA sequencing and gene-specific methylation in the hypothalamus is in progress to elucidate the mechanisms underlying the observed phenotype. Conclusions Increased maternal choline mitigates the high FA diet induced increase in body weight and food intake in the adult offspring and results in tissue-specific changes in 1-carbon metabolism at birth. These findings have potential application to human health, providing support to optimize choline and FA intakes by women of childbearing age. Funding Sources CIHR-INMD.

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Rola Hammoud ◽  
Chih-Sheng Liao ◽  
Emanuela Pannia ◽  
Mandy Ho ◽  
Neil Yang ◽  
...  

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).


Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1477
Author(s):  
Emanuela Pannia ◽  
Rola Hammoud ◽  
Ruslan Kubant ◽  
Jong Yup Sa ◽  
Rebecca Simonian ◽  
...  

Supplementation with [6S]-5-methyltetrahydrofolic acid (MTHF) is recommended as an alternative to folic acid (FA) in prenatal supplements. This study compared equimolar gestational FA and MTHF diets on energy regulation of female offspring. Wistar rats were fed an AIN-93G diet with recommended (2 mg/kg diet) or 5-fold (5X) intakes of MTHF or FA. At weaning, female offspring were fed a 45% fat diet until 19 weeks. The 5X-MTHF offspring had higher body weight (>15%), food intake (8%), light-cycle energy expenditure, and lower activity compared to 5X-FA offspring (p < 0.05). Both the 5X offspring had higher plasma levels of the anorectic hormone leptin at birth (60%) and at 19 weeks (40%), and lower liver weight and total liver lipids compared to the 1X offspring (p < 0.05). Hypothalamic mRNA expression of leptin receptor (ObRb) was lower, and of suppressor of cytokine signaling-3 (Socs3) was higher in the 5X-MTHF offspring (p < 0.05), suggesting central leptin dysregulation. In contrast, the 5X-FA offspring had higher expression of genes encoding for dopamine and GABA- neurotransmitter receptors (p < 0.01), consistent with their phenotype and reduced food intake. When fed folate diets at the requirement level, no differences were found due to form in the offspring. We conclude that MTHF compared to FA consumed at high levels in the gestational diets program central and peripheral mechanisms to favour increased weight gain in the offspring. These pre-clinical findings caution against high gestational intakes of folates of either form and encourage clinical trials examining their long-term health effects when consumed during pregnancy.


2020 ◽  
Vol 11 (4) ◽  
pp. 347-359
Author(s):  
D. Valent ◽  
L. Arroyo ◽  
E. Fàbrega ◽  
M. Font-i-Furnols ◽  
M. Rodríguez-Palmero ◽  
...  

The pig is a valuable animal model to study obesity in humans due to the physiological similarity between humans and pigs in terms of digestive and associated metabolic processes. The dietary use of vegetal protein, probiotics and omega-3 fatty acids is recommended to control weight gain and to fight obesity-associated metabolic disorders. Likewise, there are recent reports on their beneficial effects on brain functions. The hypothalamus is the central part of the brain that regulates food intake by means of the production of food intake-regulatory hypothalamic neuropeptides, as neuropeptide Y (NPY), orexin A and pro-opiomelanocortin (POMC), and neurotransmitters, such as dopamine and serotonin. Other mesolimbic areas, such as the hippocampus, are also involved in the control of food intake. In this study, the effect of a high fat diet (HFD) alone or supplemented with these additives on brain neuropeptides and neurotransmitters was assessed in forty-three young pigs fed for 10 weeks with a control diet (T1), a high fat diet (HFD, T2), and HFD with vegetal protein supplemented with Bifidobacterium breve CECT8242 alone (T3) or in combination with omega-3 fatty acids (T4). A HFD provoked changes in regulatory neuropeptides and 3,4-dihydroxyphenylacetic acid (DOPAC) in the hypothalamus and alterations mostly in the dopaminergic system in the ventral hippocampus. Supplementation of the HFD with B. breve CECT8242, especially in combination with omega-3 fatty acids, was able to partially reverse the effects of HFD. Correlations between productive and neurochemical parameters supported these findings. These results confirm that pigs are an appropriate animal model alternative to rodents for the study of the effects of HFD on weight gain and obesity. Furthermore, they indicate the potential benefits of probiotics and omega-3 fatty acids on brain function.


2016 ◽  
Vol 5 (6) ◽  
pp. 124
Author(s):  
Kouadio N. Joseph ◽  
Akoa E. Edwige ◽  
Kra K. A. Séverin ◽  
Niamke L. Sébastien

The aim of this study was to valorize senescent plantain. Therefore, a traditional dish named Dockounou was prepared with a mixture of senescent plantain and various millet, soybean, sorghum, cassava, maize or rice flours. The growth performance of several Wistar rats feed by Dockounou was followed. Thus, batches of rats were fed for 15 days with three formulations (F1, F2, F3) in proportion of 90:10, 80:20 and 75:25 (senescent plantain dough/flours) obtained after two cooking modes (dry cooking: baked ; wet cooking: boiled). The effects of these formulations were compared to control diet (C. diet). Beyond the control diet, rats fed with the soybean baked Dockounou presented, the best following growth parameters: weight gain (2.82 to 4.19 g/d), food intake (8.92 to 9.72 g/d), feed efficiency (0.10 to 0.42), proteins intake (8.28 to 19.67), proteins efficiency (0.13 to 3.15). The physicochemical and nutritive characteristics of soybean baked Dockounou were as follow: ash (2.93 ±0.15 %), proteins (10.62±0.59 %), carbohydrates (15.46±1.53 %), calcium (232.04 – 558.20 mg/100g), potassium (313.97 – 385.11 mg/100g), magnesium (42.40 – 72.22 mg/100g), sodium (211.24 – 303.85 mg/100g) and phosphorus (330.70 – 433.71 mg/100g). Also, the study showed that, two formulations, 80:20 and 75:25, have really impact on rats growth. These results suggest that soybean baked Dockounou with important proportions, 80 % and 75 %, of senescent plantain dough can be effectively used in the diet of laboratory Wistar rats regarding the good zoological performances there are obtained.


2003 ◽  
Vol 90 (3) ◽  
pp. 589-595 ◽  
Author(s):  
Wendy E. Ward ◽  
Susie Kim ◽  
W. Robert Bruce

Evidence from epidemiological and animal-feeding trials suggests that a western-style diet that is high in fat, and low in Ca, vitamin D and folic acid may result in low bone mass and poor bone quality: this leads to an increased risk of fragility fracture. The overall objective of the present study was to determine the effect of feeding a western-style diet (low in Ca (0·4 g/kg diet, Ca:P ratio 1:10), cholecalciferol (3 μg/kg diet), folic acid (0·23 mg/kg diet) and fibre (20 g/kg diet), and high in fat (200 g/kg diet)) for 17 weeks on bone mineral content (BMC) and the biomechanical bone strength of rat femurs. A secondary objective was to determine whether femurs from male and female rats (seven to eight rats per group) respond differently to the western-style diet. Male and female rats weighing 150–180 g were fed a western-style diet or a control diet for 17 weeks. At the end of the feeding trial, femur BMC was measured by ashing, and biomechanical properties were determined by three-point bending. Femur BMC and the majority of biomechanical properties measured were lower (P<0·05) among male and female rats fed a western-style diet compared with a control diet, despite similar weight gain and final body weight within genders. However, the western-style diet had a greater negative effect on femur BMC and biomechanical strength properties among male rats compared with females. This may be because male rats experienced greater overall body growth, as assessed by weight gain, than female rats, and suggests that the nutrient composition of the western-style diet did not support the development of strong femurs.


2002 ◽  
Vol 75 (3) ◽  
pp. 379-385 ◽  
Author(s):  
I. -T. Yu ◽  
J. -F. Wu ◽  
P. -C. Yang ◽  
C. -Y. Liu ◽  
D. -N. Lee ◽  
...  

AbstractThis study examined the effects of glutamine and nucleotides on growth, intestinal villous height and immune responses of weaned pigs. Eighty weaned pigs (Landrace ✕ Yorkshire ✕ Duroc) were randomly assigned to five treatments, including a control diet and a 2 (glutamine 1·0 and 1·5%) by 2 (nucleotides 500 and 1000 p.p.m.) factorial design. There were no differences among the five treatments in weight gain from weeks 0 to 4 and 0 to 8 of the experiment. However, the food intake of treatment 3 (glutamine 1·0% and nucleotides 1000 p. p. m. ) for weeks 4 to 8 was higher (P < 0·05) than that of the control group. Intestinal villous height, and serum immunoglobulin-G concentration 2 h post lipopolysaccharide injection, were higher (P < 0·05) for pigs administered treatment 3 than for controls. Furthermore, foot and mouth disease (FMD) neutralizing antibody titres were also higher (P < 0·05) than the control group for pigs given treatment 3 when measured 3 weeks following vaccination with FMD antigen. These observations suggest that a combination of 10% of glutamine and 1000 p. p. m. of nucleotides in the diet could improve food intake and intestinal villous height and promote the immune responses and FMD antibody titres of weaned pigs.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1230-1230
Author(s):  
Emanuela Pannia ◽  
Rola Hammoud ◽  
Ruslan Kubant ◽  
Rebecca Simonian ◽  
Zdenka Pausova ◽  
...  

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.


2009 ◽  
Vol 103 (7) ◽  
pp. 996-1007 ◽  
Author(s):  
Sarah F. Engeham ◽  
Andrea Haase ◽  
Simon C. Langley-Evans

Maternal protein restriction in rat pregnancy is associated with altered feeding behaviour in later life. When allowed to self-select their diet, rats subject to prenatal undernutrition show an increased preference for fatty foods. The main aim of the present study was to evaluate the contribution of folic acid in the maternal diet to programming of appetite, since disturbances of the folate and methionine–homocysteine cycles have been suggested to impact upon epigenetic regulation of gene expression and hence programme long-term physiology and metabolism. Pregnant rats were fed diets containing either 9 or 18 % casein by weight, with folate provided at either 1 or 5 mg/kg diet. Adult male animals exposed to low protein (LP) in fetal life exhibited increased preference for high-fat food. Providing the higher level of folate in the maternal diet prevented this effect of LP, but offspring of rats fed 18 % casein diet with additional folate behaved in a similar manner to LP-exposed animals. Among day 20 gestation fetuses, it was apparent that both protein restriction and maternal folate supplementation could have adverse effects upon placental growth. Examination of methionine–homocysteine and folate cycle intermediates, tissue glutathione concentrations and expression of mRNA for methionine synthase, DNA methyltransferase 1 and methyltetrahydrofolate reductase revealed no gross disturbances of folate and one-carbon metabolism in either maternal or fetal tissue. The present findings indicated that any role for DNA methylation in programming of physiology is not related to major perturbations of folate metabolism, and is likely to be gene-specific rather than genome-wide.


Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 48
Author(s):  
Emanuela Pannia ◽  
Rola Hammoud ◽  
Rebecca Simonian ◽  
Erland Arning ◽  
Paula Ashcraft ◽  
...  

[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.


Author(s):  
Abere DV

The study investigated the effect of feeding high and low saturated fatty acid based diets to feed female albino rats (Rattusnorvegicus) with a view to evaluating the effects of the fatty diets on the feeding patterns, weight and body composition of the rats. Seven months old female Rattus norvegicus were used for the experiment. The weights of the rats were taken for twelve weeks using Salter balance (Model 250). Four experimental diets were formulated which were made up of 2.5 and 5.0 g of margarine (blue band), 2.5 and 5.0 g canola oil each mixed with the basal diet. The control diet was grower feed and the resultant experimental diets were fed to the experimental rats kept in cages at the rate of 12 rats per cage. The rats were fed with the diets at the rate of 3% of body weight for a period of twelve weeks. The highest weight gain was recorded in the group fed with 5.0 g margarine, followed by 5.0 g canola, 2.5 g margarine, 2.5 g canola and least in the rats fed the control.The mean weight gain of the rats fed with 5.0 g margarine and 5.0 g canola were significantly different (p<0.05) from the mean weight of 2.5 g margarine, 2.5 g canola and the control. The food intake of the rats fed 5.0 g margarine and 5.0 g canola was also significantly different (p<0.05) from the food intake of rats fed 2.5 g margarine, 2.5 g canola and the control. The proximate composition of the carcass of the rats fed the different experimental diets showed that fat content of the rats fed 5.0 g margarine was higher than in the rats fed the other diets. The histology of the liver of rats fed 5.0 g margarine and 5.0 g canola showed greater fat accumulation in the rat’s liver compared to rats fed 2.5 g margarine, 2.5 g canola as well as the control. Rats with the highest body weight gain were considered obesity-prone; those with the lowest body weight were regarded as obesity-resistant while others were considered intermediate. The study concluded that the kind of fat consumed contributes to the weight gained by the rats.


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