PPARGC1α gene DNA methylation variations in human placenta mediate the link between maternal hyperglycemia and leptin levels in newborns
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Bibliographic record
Abstract
BACKGROUND: Children exposed to gestational diabetes mellitus (GDM) are at a higher risk of developing obesity and type 2 diabetes. This susceptibility might involve brown adipose tissue (BAT), which is suspected to protect against obesity. The objective of this study is to assess whether fetal exposure to maternal hyperglycemia is associated with DNA methylation variations in genes involved in BAT genesis and activation. METHODS: DNA methylation levels at the PRDM16, BMP7, CTBP2, and PPARGC1α gene loci were measured in placenta samples using bisulfite pyrosequencing in E-21 (n = 133; 33 cases of GDM) and the HumanMethylation450 array in Gen3G (n = 172, all from non-diabetic women) birth cohorts. Glucose tolerance was assessed in all women using an oral glucose tolerance test at the second trimester of pregnancy. Participating women were extensively phenotyped throughout pregnancy, and placenta and cord blood samples were collected at birth. RESULTS: We report that maternal glycemia at the second and third trimester of pregnancy are correlated with variations in DNA methylation levels at PRDM16, BMP7, and PPARGC1α and with cord blood leptin levels. Variations in PRDM16 and PPARGC1α DNA methylation levels were also correlated with cord blood leptin levels. Mediation analyses support that DNA methylation variations at the PPARGC1α gene locus explain 0.8 % of the cord blood leptin levels variance independently of maternal fasting glucose levels (p = 0.05). CONCLUSIONS: These results suggest that maternal glucose in pregnancy could produce variations in DNA methylation in BAT-related genes and that some of these DNA methylation marks seem to mediate the impact of maternal glycemia on cord blood leptin levels, an adipokine regulating body weight.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it