Hyper-proliferation of Adipose Progenitors During Developmental Adipogenesis Programs Higher Adipocyte Number and Early-onset Obesity in Offspring Born to Obese Dams
Bibliographic record
Abstract
ABSTRACT Being born to a mother who was obese during pregnancy is one of the strongest predictors of early onset obesity and metabolic syndrome. To identify the developmental mechanism linking maternal obesity to cardiometabolic disease in the offspring, a high fat/high fructose diet or low-fat control diet were introduced 4 weeks prior to mating in C57BL6 females and continued throughout pregnancy and lactation. Offspring born to obese dams had greater whole-body adiposity prior to puberty and were more susceptible to diet-induced obesity in adulthood. On postnatal day 10 (PND10) when pups born to obese dams had greater accumulation of subcutaneous adipose tissue, single cell sequencing was used to identify adipose progenitor cells (APCs) in the stromal vascular fraction. Two distinct lineages of APCs were identified that arose from a common proliferative root, terminating in committed preadipocytes and anti-adipogenic APCs. In pups born to obese dams, the proliferative root made up a greater proportion of APCs, more of these cells were in the G2M and S phases of the cell cycle and there was an enrichment in genes associated with proliferation ( mKi67, Fat3, Ccn4, Gata4 ). On PND10, APCs isolated from the inguinal depots of pups born to obese dams were hyper-proliferative and there was a greater abundance of total APCs, whereas there were no differences in adipocyte size. After puberty, APCs in subcutaneous depots of offspring born to obese dams were more adipogenic in vitro and this group gained a greater amount of body fat in response to pharmacological stimulation of adipogenesis by rosiglitazone. Male adults born to obese dams had a lower abundance of APCs and were more susceptible to APC exhaustion due to prolonged exposure to rosiglitazone. Therefore, early onset obesity in offspring exposed to maternal obesity in utero is due to a prolongation of the proliferative phase of early life adipogenesis, leading to a higher adipocyte number.
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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 | 0.001 | 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) | 0.002 | 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".