Regular exercise reduces adipose tissue inflammation and improves glycemic control in Western diet‐fed mice despite hyperendothelinemia
Bibliographic record
Abstract
The upregulation of endothelin‐1 (ET‐1), a peptide primarily expressed and secreted into the circulation from endothelial cells, is a key molecular signature in obesity and type 2 diabetes. Given its potent pro‐oxidant and inflammatory effects, ET‐1 is thought to be implicated in the etiology of metabolic dysfunction. Based on previous evidence that regular exercise decreases ET‐1 expression and signaling, it is conceivable that the well‐established exercise‐induced anti‐inflammatory effects and associated improvement in glycemic control is, in part, mediated by a reduction in ET‐1 actions; however, this remains unknown. Accordingly, we tested the hypothesis that overproduction of ET‐1 from endothelial cells and resulting hyperendothelinemia limits the beneficial metabolic adaptations of exercise. Six‐week‐old male transgenic mice overexpressing human preproET‐1 selectively in the endothelium (eET‐1) and non‐transgenic (i.e., wild‐type) littermates were fed a Western diet (46% Kcal fat, 36% Kcal carbohydrate) to induce obesity, while they either remained sedentary or had free access to a running wheel for 12 weeks, creating four groups (n=7–12/group): wild‐type sedentary, wild‐type exercise, eET‐1 sedentary, eET‐1 exercise. Plasma ET‐1 was significantly elevated in eET‐1 mice (sedentary: 15.12±3.77 pg/ml; exercise 14.90±2.30 pg/ml) versus wild‐type (sedentary: 0.02±0.02 pg/ml; exercise: 0.29±0.14 pg/ml) in both sedentary and exercise‐trained mice. Exercise reduced final body weight, adiposity, fasting plasma insulin, HOMA‐IR, cholesterol and triglycerides compared to sedentary mice, and these effects were independent of genotype. Also independent of genotype, exercise reduced visceral adipocyte hypertrophy, immune cell infiltration, inflammatory gene expression (e.g., IL‐1β and CD11c), as well as enhanced visceral adipose tissue insulin signaling (i.e., increased ex vivo insulin‐stimulated pAkt/Akt). Furthermore, exercise improved glucose tolerance and this improvement was mildly enhanced in eET‐1 mice (i.e., significant genotype × exercise interaction). In summary, contrary to our hypothesis, we find that experimentally‐induced hyperendothelinemia does not impede exercise‐induced improvements in metabolic function, supporting the notion that reduced ET‐1 signaling is not required for the beneficial metabolic adaptations of exercise to manifest. Support or Funding Information National Institute of Health This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| 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".