Interaction of uteroplacental insufficiency and postnatal Western diet on the hepatic transcriptome in young adult female and male Guinea pigs
Bibliographic record
Abstract
Epidemiological and animal studies highlight an adverse in utero environment, often associated with low birth weight (LBW) and intrauterine growth restriction (IUGR), and postnatal intake of energy-dense foods, interact in the development of nonalcoholic fatty liver disease (NAFLD) in offspring. While these associations are emerging, understanding the specific contributions of LBW/IUGR and energy-dense food such as Western diet (WD) to the hepatic transcriptome and development of NAFLD is lacking. This study used a guinea pig model of uteroplacental insufficiency (UPI) to induce LBW/IUGR. It applied microarray-based expression profiling with epigenetic marker analysis to explore mechanisms by which UPI may predisposes WD-fed young adult offspring to NAFLD. At postnatal day 150, male and female WD offspring exhibited lean NAFLD, regardless of birth weight. WD consumption led to downregulation of the steroid biosynthesis, upregulation of ECM-receptor interaction, cell cycle, lysosome, and AGE-RAGE signaling pathways in both sexes. Additionally, genes in the p53 signaling pathway were upregulated in WD males, while the PPAR signaling pathway was upregulated in WD females, independent of birth weight. MicroRNA (miR)–target gene interactions and RTqPCR analyses revealed that miR-26b-5p in males and miR-29-3p in females were linked to these pathway changes. The combination of LBW and WD caused changes in hepatic adrenergic and calcium signaling in females and NF-kappa beta signaling in males. This study shows that although LBW and WD each uniquely and jointly affect the hepatic transcriptome, WD alone appears to be a significant environment underlying NAFLD in young adult female and male guinea pigs. • Guinea pigs displayed a lean NAFLD phenotype on a Western diet (WD), irrespective of birth weight. • Both sexes had increased liver weight, triglycerides and collagen deposition when consuming a WD, independent of birth weight. • WD impacted steroid biosynthesis, ECM-receptor interaction and cholesterol metabolism pathways in both sexes. • WD low birth weight (LBW) males and females showed NF-κB and calcium signalling changes, respectively. • miR-26b (males) and miR-29-3p (females) were linked to pathway changes via miR–gene interactions and RT-qPCR.
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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 | 0.000 |
| 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".