scholarly journals Supplementation of a maternal low-protein diet in rat pregnancy with folic acid ameliorates programming effects upon feeding behaviour in the absence of disturbances to the methionine–homocysteine cycle

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.

2008 ◽  
Vol 101 (7) ◽  
pp. 1020-1030 ◽  
Author(s):  
Matthew Harrison ◽  
Simon C. Langley-Evans

Associations between birth weight and CVD in adult life are supported by experiments showing that undernutrition in fetal life programmes blood pressure. In rats, the feeding of a maternal low-protein (MLP) diet during gestation programmes hypertension. The present study aimed to assess the potential for a nutritional insult to impact across several generations. Pregnant female Wistar (F0) rats were fed a control (CON;n10) or MLP (n10) diet throughout gestation. At delivery all animals were fed a standard laboratory chow diet. At 10 weeks of age, F1generation offspring were mated to produce a second generation (F2) without any further dietary change. The same procedure produced an F3generation. Blood pressure in all generations was determined at 4, 6 and 8 weeks of age and nephron number was determined at 10 weeks of age. F1generation MLP-exposed offspring exhibited raised (P < 0·001) systolic blood pressure (male 143 (sem4) mmHg; female 141 (sem4) mmHg) compared with CON animals (male 132 (sem3) mmHg; female 134 (sem4) mmHg). Raised blood pressure and reduced nephron number was also noted in the F2generation (P < 0·001) and this intergenerational transmission occurred via both the maternal and paternal lines, as all three possible offspring crosses (MLP × CON, CON × MLP and MLP × MLP) were hypertensive (132 (sem3) mmHg) compared with CON animals (CON × CON; 123 (sem2) mmHg). No effect was noted in the F3generation. It is concluded that fetal protein restriction may play a critical role in determining blood pressure and overall disease risk in a subsequent generation.


2005 ◽  
Vol 109 (4) ◽  
pp. 413-420 ◽  
Author(s):  
Leanne Bellinger ◽  
Simon C. Langley-Evans

Undernutrition in fetal life programmes risk of obesity and the metabolic syndrome in adult life. Rat studies indicate that exposure to a maternal low-protein diet throughout fetal life establishes a preference for high-fat foods. The present study aimed to assess the effect of low protein exposure during discrete 7-day periods of gestation upon feeding behaviour (full gestation 22 days). Pregnant rats were fed control or low-protein diet, with low-protein feeding targeted at day 0–7 (LPEarly), day 8–14 (LPMid) or day 15–22 (LPLate) of gestation. At 12 weeks of age, offspring were placed on a macronutrient self-selection regimen. Prenatal protein restriction programmed feeding behaviour in female, but not male, offspring. Among females, all low-protein exposed groups consumed less fat than the control group (P<0.05). Male offspring showed no changes in feeding behaviour. In males and females fed a low-fat chow diet, there were metabolic differences between the groups. LPEarly and LPLate males had greater hepatic glycogen stores than control animals. There were no differences in the size of abdominal fat depots in either male or female rats exposed to low-protein diet at any point in gestation. The data suggest that programming of feeding behaviour is likely to be gender-specific and dependent upon the timing of nutrient insult in fetal life. This work may have implications for the development of the metabolic syndrome.


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 &lt; 0.05) and weight-gain (P &lt; 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 &lt; 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.


2021 ◽  
Vol 12 ◽  
Author(s):  
Letícia de Barros Sene ◽  
Gabriela Leme Lamana ◽  
Andre Schwambach Vieira ◽  
Wellerson Rodrigo Scarano ◽  
José Antônio Rocha Gontijo ◽  
...  

BackgroundThe kidney ontogenesis is the most structurally affected by gestational protein restriction, reducing 28% of their functional units. The reduced nephron number is predictive of hypertension and cardiovascular dysfunctions that are generally observed in the adult age of most fetal programming models. We demonstrate miRNAs and predict molecular pathway changes associated with reduced reciprocal interaction between metanephros cap (CM) and ureter bud (UB) and a 28% decreased nephron stem cells in the 17 gestational days (17GD) low protein (LP) intake male fetal kidney. Here, we evaluated the same miRNAs and predicted targets in the kidneys of 21GD and at 7 days of life (7DL) LP offspring to elucidate the molecular modulations during nephrogenesis.MethodsPregnant Wistar rats were allocated into two groups: NP (regular protein diet- 17%) or LP (diet-6%). miRNA transcriptome sequencing (miRNA-Seq) was performed on the MiSeq platform from 21GD and 7DL male offspring kidneys using previously described methods. Among the top 10 dysfunctional regulated miRNAs, we validated 7 related to proliferation, differentiation, and apoptosis processes and investigated predicted target genes and proteins by RT-qPCR and immunohistochemistry.ResultsIn 21GD, LP fetuses were identified alongside 21 differently expressed miRNAs, of which 12 were upregulated and 9 downregulated compared to age-matched NP offspring. In 7-DL LP offspring, the differentially expressed miRNAs were counted to be 74, of which 46 were upregulated and 28 downregulated. The curve from 17-GD to 7-DL shows that mTOR was fundamental in reducing the number of nephrons in fetal kidneys where the mothers were subjected to a protein restriction. IGF1 and TGFβ curves also seemed to present the same mTOR pattern and were modulated by miRNAs 181a-5p, 181a-3p, and 199a-5p. The miRNA 181c-3p modulated SIX2 and Notch1 reduction in 7-DL but not in terms of the enhanced expression of both in the 21-GD, suggesting the participation of an additional regulator. We found enhanced Bax in 21-GD; it was regulated by miRNA 298-5p, and Bcl2 and Caspase-3 were controlled by miRNA (by 7a-5p and not by the predicted 181a-5p). The miRNA 144-3p regulated BCL6, which was enhanced, as well as Zeb 1 and 2 induced by BCL6. These results revealed that in 21GD, the compensatory mechanisms in LP kidneys led to the activation of UB ramification. Besides, an increase of 32% in the CM stem cells and a possible cell cycle halt of renal progenitor cells, which remaining undifferentiated, were observed. In the 7DL, much more altered miRNA expression was found in LP kidneys, and this was probably due to an increased maternal diet content. Additionally, we verified the activation of pathways related to differentiation and consumption of progenitor cells.


2020 ◽  
pp. 1-28
Author(s):  
H.Q. Li ◽  
B. Wang ◽  
Z. Li ◽  
H.L. Luo ◽  
C. Zhang ◽  
...  

Abstract This study was undertaken to evaluate the influence of rumen-protected folic acid (RPFA) on slaughter performance, visceral organ and gastrointestinal tract coefficients, and meat quality in lambs. Sixty-six lambs from 120 Hu ewes were selected based on body weight and maternal diets, and then assigned to six groups using a randomized block experimental design in a 3 × 2 factorial arrangement. The first factor was folic acid (FA) as RPFA in the maternal diet (0 mg/kg [M0F], 16 mg/kg [M16F] or 32 mg/kg [M32F] on dry matter basis). The second factor was FA in the lambs’ diet from weaning until slaughter (0 mg/kg [OC] or 4.0 mg/kg [OF]). The results indicated that the addition of 16 mg/kg FA to the maternal diet increased pre-slaughter weight (PSW), dressing and meat percentage, the reticulum and omasum coefficients, length of the jejunum and ileum, tail fat and perirenal fat coefficient and a* value of the meat color. The addition of RPFA to the lambs’ diet increased PSW, dressing and meat percentage, eye muscle area, abomasum weight, weight and length of the small intestine, but reduced the coefficients of tail fat. A M×O interaction was observed for the weights of heart, lungs, rumen and total stomach, weight and coefficient of omental fat and the GR value. Collectively, RPFA in the maternal and lambs’ diet improved slaughter performance and meat quality by stimulating the morphological development of the gastrointestinal tract and the distribution of fat in the body.


2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Aditi Sen ◽  
Shubhada Kanani

In view of high iron needs for adolescent growth, this paper studied the impact of daily vs. intermittent (once and twice weekly) iron folic acid (IFA) supplementation on hemoglobin levels and pubertal growth among primary school girls in early adolescence (9–13 years) of Vadodara, India. Methods. Hemoglobin (Hb), height and weight of the girls were assessed using standard methods. In three experimental schools (ES) IFA tablets in a dose of 100 mg Fe+0.5 mg folic acid was given either daily, once weekly or twice weekly for one year. The fourth school (control: CS) did not receive any intervention. Results. Hb levels significantly improved (P<0.01) in all ES compared to CS. Body Mass Index (BMI) increment in ES vs CS was significant (P<0.05) in twice weekly IFA and daily IFA. Within ES groups, mean Hb and BMI increments were comparable between twice weekly IFA and daily IFA. Anemic ES girls showed higher Hb and BMI increments vs. non-anemic girls. Better the Hb response, greater was the benefit on BMI. Conclusion: Twice-weekly IFA supplementation was comparable to daily IFA as regards impact on Hb and growth; at less cost and greater feasibility. Once-weekly dose was inadequate to significantly improve growth.


Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1354
Author(s):  
Antioco Fois ◽  
Massimo Torreggiani ◽  
Tiziana Trabace ◽  
Antoine Chatrenet ◽  
Elisa Longhitano ◽  
...  

Prescribing a low-protein diet (LPD) is part of the standard management of patients in advanced stages of chronic kidney disease (CKD). However, studies on the quality of life (QoL) of patients on LPDs are lacking, and the impact these diets have on their QoL is often given as a reason for not prescribing one. We, therefore, decided to assess the QoL in a cohort of CKD stage 3–5 patients followed up by a multiple-choice diet approach in an outpatient nephrology clinic in France. To do so, we used the short version of the World Health Organization’s quality of life questionnaire and compared the results with a historical cohort of Italian patients. We enrolled 153 patients, managed with tailored protein restriction in Le Mans, and compared them with 128 patients on similar diets who had been followed in Turin (Italy). We found there were no significant differences in terms of age (median 73 vs. 74 years, respectively), gender, CKD stage, and comorbidities (Charlson’s Comorbidity Index 7 vs. 6). French patients displayed a greater body mass index (29.0 vs. 25.4, p < 0.001) and prevalence of obesity (41.2 vs. 15.0%, p < 0.001). Baseline protein intake was over the target in France (1.2 g/kg of real body weight/day). In both cohorts, the burden of comorbidities was associated with poorer physical health perception while kidney function was inversely correlated to satisfaction with social life, independently of the type of diet. Our study suggests that the type of LPD they follow does not influence QoL in CKD patients and that a personalized approach towards protein restriction is feasible, even in elderly patients.


2007 ◽  
Vol 292 (5) ◽  
pp. E1318-E1324 ◽  
Author(s):  
Lucie Šedová ◽  
Ondřej Šeda ◽  
Ludmila Kazdová ◽  
Blanka Chylíková ◽  
Pavel Hamet ◽  
...  

The importance of early environment, including maternal diet during pregnancy, is suspected to play a major role in pathogenesis of metabolic syndrome and related conditions. One of the proposed mechanisms is a mismatch between the prenatal and postnatal environments, leading to misprogramming of the metabolic and signaling pathways of the developing fetus. We assessed whether the exposure to high-sucrose diet (HSD) alleviates the detrimental effects of sucrose feeding in later life (predictive adaptive hypothesis) in a highly inbred model of metabolic syndrome, the PD/Cub rat. Rat dams were continuously fed either standard or HSD (70% calories as sucrose) starting 1 wk before breeding, throughout pregnancy, at birth, and until weaning of the offspring. After weaning, all male offspring were fed HSD until the age of 20 wk, when detailed metabolic and morphometric profiles were ascertained. The early life exposure to a sucrose-rich diet resulted in distinct responses to longtime postnatal HSD feeding. Offspring of the sucrose-fed mothers displayed higher adiposity and substantial increases in triglyceride liver content together with unfavorable distribution of cholesterol into lipoprotein subfractions. On the other hand, their adiponectin concentrations were significantly higher, and insulin sensitivity of skeletal muscle was enhanced compared with the offspring of standard diet-fed mothers. Triglycerides, free fatty acids, overall glucose tolerance, and the insulin sensitivity of adipose tissue were comparable in both groups. In the genetically identical animals, maternal HSD feeding elicited a variety of subtle effects but did not lead to predictive adaptive protection from most HSD-induced metabolic derangements.


1997 ◽  
Vol 127 (2) ◽  
pp. 202-209 ◽  
Author(s):  
Simon C. Langley-Evans ◽  
Gary J. Phillips ◽  
Alan A. Jackson

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