Adipose Tissue – Skeletal Muscle Crosstalk: Obese Human Subcutaneous and Visceral Adipose Tissues Both Supress Muscle Insulin Signalling in Men and Women
Bibliographic record
Abstract
Adipose tissue is an important endocrine organ that communicates with other peripheral tissues via the secretion of proteins, termed adipokines. In particular, altered secretion of specific adipokines (e.g., TNF‐α and adiponectin) has previously been shown to regulate skeletal muscle insulin sensitivity. For the current study, we established a human adipose tissue – muscle crosstalk model to investigate the impact of different adipose tissue depots on skeletal myocyte insulin signaling, and if this differs between men and women. Visceral (VAT) and subcutaneous (SAT) adipose tissue samples were collected from obese men and women during laparoscopic bariatric surgery. Adipose tissue samples were subsequently cultured for 48h and secretion media was collected. Secretion media was then transferred on to human skeletal myocytes derived from healthy, non‐diabetic male and female donors for 24h. Content of insulin signaling proteins (phosphorylated and total AKT) in mature myocytes incubated with either control M199 media or secretion media from VAT or SAT was assessed using Western Blotting in basal and insulin‐stimulated conditions (100uU/well). Adipokines in secretion media were measured with a multiplex immunoassay. In men, VAT had higher interleukin‐6 gene expression compared to SAT (p=0.004), while no differences were seen in women (p=0.271). Adiponectin and TNF‐α gene expression were not different between VAT or SAT for men or women. Secretion media collected from male SAT and VAT reduced p‐AKT Thr308 activation in insulin‐stimulated myocytes compared to controls (p <0.01). Interestingly, myocytes incubated with VAT secretion media, compared to SAT secretion media, showed a significant reduction in p‐AKT Ser473 in men after insulin stimulation (p<0.01). Secretion media collected from female VAT and SAT caused significant reductions in p‐AKT Thr308 and p‐AKT Ser473 activation following insulin stimulation, compared to controls (p<0.01). Secretion media from VAT or SAT for men or women did not affect total‐AKT levels. Independent of sex, 14 out of 18 detected adipokines (i.e., a panel consisting of cytokines, chemokines and growth factors) were more abundant in VAT secretion media compared to SAT secretion media (p<0.01). Only interleukin‐21 levels showed a sex difference, with higher levels detected in secretion media from female adipose tissue (p=0.003). In conclusion, SAT and VAT secretion media from obese men and women suppress insulin signaling in myocytes to a similar extent. These results reveal the power of this human adipose tissue – muscle model to investigate crosstalk between these two tissues. Support or Funding Information This work was supported by the Natural Sciences and Engineering Research Council of Canada.
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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 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.006 | 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".