Abstract 3559: Gene-expression changes in adipose tissue with diet- and/or exercise-induced weight loss: a randomized controlled trial
Bibliographic record
Abstract
Abstract Background: Adipose tissue (AT) plays a role in obesity-related disease pathogenesis via increased production of inflammatory factors, steroid hormones, and altered lipid metabolism. The impact of diet and/or exercise induced weight loss on AT gene expression will provide key insights into the pathways linking obesity with metabolic disease. Methods: We conducted an ancillary study within a randomized trial of calorie-reduced diet (D), exercise (E), or combined diet and exercise (D+E) vs control among overweight/obese postmenopausal women (Nutrition and Exercise for Women Study). Subcutaneous AT was biopsied at baseline and 6 months from 47 women. Gene expression was measured by the Illumina BeadChip WG-6 and interrogated for changes in candidate genes, and all array-based genes. Analyses were conducted by intervention group and by weight-loss group. Results: Participants were aged 58.3±4.7 years; with a mean BMI of 31.1±4.3 kg/m2. At 6 month, controls were weight-stable while D, E, and D+E participants lost on average 8.8 kg, 2.5 kg, and 7.9 kg (all P<0.05 vs control). There were no significant changes in candidate gene expression by intervention group. When all participants were analyzed by weight loss, in the group with >10% weight loss there was a progressive decrease in 17α hydroxysteroid dehydrogenase-1 (-35% p-trend=0.0002), steroid sulfatase (-26%, p-trend=0.02), 17α hydroxysteroid dehydrogenase-10 (-5%, p-trend=0.045), intercellular adhesion molecule 4 (-9%, p-trend=0.01), serum amyloid A (-38%, p-trend=0.01), and leptin (-44%, p-trend=0.00003) expression, with trends towards increased expression of estrogen receptor-1 (24% p-trend=0.004), C-reactive protein (23%, p-trend 0.008), vascular cell adhesion molecule 1 (34%, p-trend=0.04) and insulin-like growth factor (IGF) binding protein-3 (37%; p-trend=0.003). The unsupervised clustering of >37.000 transcripts by weight loss revealed 78 transcripts with statistically significant adjusted p-values. Leptin, the strongest signal in our candidate-gene analysis, was the 33rd strongest hit in this clustering. Conclusions: A 6-month lifestyle intervention caused weight loss with corresponding changes in AT gene expression, particularly steroid-hormone metabolism and IGF signaling, both pathways postulated to link obesity and cancer. Leptin is a primary signaling target of weight loss in adipose tissue, but weight change altered also a number of other biologic pathways in adipose tissue which requires further investigation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3559. doi:1538-7445.AM2012-3559
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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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.009 | 0.001 |
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".