Effects of a Low-protein Diet with Varying Methionine Levels During Pregnancy on Litter Size, Fetal Weight, and Amino Acid Metabolism.
Bibliographic record
Abstract
Feeding a low-protein, casein-based, methionine (MET) supplemented diet to pregnant rats is a well-established model to study developmental programming. Currently, the mechanisms leading to these reprogramming events are unresolved; one possible explanation is that the higher supplemental MET in the low-protein diet could disrupt one-carbon (1-C) metabolism at the level of the mother, the fetus or both. Since 1-C metabolism, involving such events as nucleoside synthesis and epigenetic transfers, is especially critical during the embryonic/ fetal period of life, it seems plausible that disruption of these processes could result in the long-term reprogramming of offspring observed. We propose that a low-protein high-MET diet will disrupt 1-C metabolism in dams and/or fetuses. Phase one of this study presents plasma amino acid profiles of dams at day 20 of gestation. Wistar rats were fed ad libitum, commencing on day zero of pregnancy, one of three diets: 18% casein with 0.5% supplemental MET (18-0.5, "control"; n=6), 9% casein with either 0.5% or 1.0% supplemental MET (9-0.5; n=6 and 9-1.0; n=6, respectively). Food consumption and maternal weight gain were monitored throughout the study. On day 20 of gestation, subsequent to maternal euthanasia, fetuses were excised and weighed and litter size was assessed. Maternal and fetal plasma, livers and kidneys were collected. Plasma free amino acid profiles were determined by HPLC using the Pico-Tag method (Waters). No significant differences were observed in food consumption, maternal weight gain or litter sizes (18-0.5: 14.3±0.7; 9-0.5: 14.5±0.9; 9-1.0: 12.4±1.6 fetuses). Fetal weights were unaffected by diet. Surprisingly, levels of the toxic, non-protein, sulfur-containing amino acid homocysteine (HCY), which serves to connect the folate and MET cycles in 1-C metabolism, did not differ significantly (18-0.5: 30±8; 9-0.5: 43±11; 9-1.0: 52±6 μM). However, maternal plasma MET levels were elevated by 42% in both 9-0.5 and 9-1.0 (respectively 148±23; 149±10 μM; p<0.05) compared to the control diet (86±12). Threonine (THR), the catabolism of which can be used to increase folate supply, was decreased in 9-0.5 by 47% and by 57% in 9-1.0 (respectively 186±24; 151±19 μM; p<0.001) compared to controls (18-0.5: 355±24), but levels were not significantly different between the low-protein diets. Relative to the control group, serine (SER) and glycine (GLY), two amino acids which are catabolised in the regeneration of methylated folates, tended to be reduced in 9-1.0 (respectively p=0.06; p=0.08), with GLY tending to be further reduced in 9-1.0 relative to 9-0.5 (p=0.08). Together, these results indicate a possible disruption of 1-C metabolism, specifically at the intersection of the MET and folate cycles. Decreases in plasma THR, SER and GLY, in combination with the increased plasma MET and unaltered plasma HCY suggests usage of 5-methyl-tetrahydrofolate for HCY re-methylation. Thus, regulation of plasma levels of HCY may be achieved at the expense of creating a functional folate deficiency within dams of the 9-0.5 and 9-1.0 treatment groups. Reprogramming could result from the impaired folate status, or through interactive effects of depleted folates and reduced dietary protein. Further assessment of 1-C metabolism disruption at the fetal and maternal level is currently underway. (platform)
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".