Sex steroid hormones induce acylation stimulating protein resistance in 3T3‐L1 adipocytes
Bibliographic record
Abstract
Acylation stimulating protein (ASP) stimulates triglyceride synthesis and glucose transport via its receptor C5L2. In human studies, ASP is increased in insulin resistant states such as obesity, diabetes, polycystic ovary syndrome and late pregnancy (the latter two associated with altered sex hormones). The aims were (i) to evaluate ASP response and C5L2 expression following treatment with sex steroid hormones and (ii) to identify mechanisms of ASP resistance using 3T3-L1 adipocytes and preadipocytes. Overnight incubation with physiological progesterone (PROG) concentrations induced dose-dependent inhibition of ASP-stimulated glucose transport in adipocytes (188 +/- 11% +ASP, 100 +/- 4% control, 129 +/- 18% to 85 +/- 7% [ASP + PROG 10(-8) to 10(-6) M] and preadipocytes (263 +/- 18% +ASP, 100 +/- 3% control, 170 +/- 11% to 167 +/- 4% [ASP + PROG 10(-8) to 10(-6) M]), while estradiol and testosterone (TEST) were effective only at the highest concentration (10(-6) M). In adipocytes, dose-dependent maximal C5L2 mRNA decreases were 39-75% (P = 0.003), with decreased cell-surface C5L2 of -22% and -27% (10(-6) M PROG and TEST, respectively) with no change in preadipocytes. Adipocytes treated with PROG displayed decreases in G proteins: Gbeta (-55%), Galphaq/11 (-56%) as well as complete inhibition of ASP stimulation. PROG significantly decreased basal levels of phosphorylated PKCalpha (p-PKCalpha) while there was no change in p- PKCzeta. ASP increased p-PKCalpha and PKCzeta to 161% (P < 0.0.001) and 160% (P < 0.01), a stimulation effectively blocked by PROG (10(-8) and 10(-6) M) and TEST (10(-6) M). Sex steroid hormone-induced ASP resistance via C5L2 may contribute to altered adipose tissue function and insulin resistance phenotype in humans.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".