1222-P: Adipose Tissue Antilipolytic Insulin Sensitivity Protects against Whole-Body Insulin Resistance and Lowers Acylcarnitine Accumulation in Adults with Obesity
Bibliographic record
Abstract
The aims of this study were; 1) to assess clinical and subclinical factors associated with insulin-stimulated glucose uptake and 2) compare skeletal muscle lipid profile (untargeted lipidomics) in a sub-cohort of insulin sensitive vs. insulin resistant subjects. 66 obese adults (F=46 [BMI=34±3kg/m2], M=20 [BMI=33±2.9 kg/m2]) with homogeneous body composition completed a 2h hyperinsulinemic-euglycemic clamp, and stable isotope dilution methods to assess glucose rate of disappearance (Glucose Rd: index of insulin sensitivity), fatty acid rate of appearance (FA Ra), and hepatic glucose production (Glucose Ra) under basal and hyperinsulinemic conditions. We also performed an array of metabolic measurements (e.g., hepatic and visceral fat accumulation [via MRI], fat oxidation, lipid profile, circulating cytokines). Covariate analysis (LASSO) identified insulin-mediated suppression of FA Ra, basal glucose Ra, and fat oxidation as the cluster of measurements best predicting Glucose Rd (r=0.76, p<0.01). Insulin-mediated suppression of FA Ra was also the strongest independent predictor of Glucose Rd (r=0.51; p<0.01). As a result of greater adipose tissue anti-lipolytic response to insulin, lower FA delivery to skeletal muscle may improve insulin-mediated glucose uptake via lower muscle lipid accumulation. Importantly, we found the accumulation of several long-chain acylcarnitine species (measure of incomplete β-oxidation: C18:0,18:1,20:1,20:3) to be lower (p<0.05) in muscle samples from an insulin sensitive sub-cohort (Glucose Rd > 8.5 µmol/(min•FFM•[Insulin]); n=10) compared with an insulin resistant sub-cohort (< 7.2 µmol/(min•FFM•[Insulin]); n=8). In conclusion, our findings indicate that greater adipose tissue anti-lipolytic response to insulin is an important predictor of insulin-mediated glucose uptake - and acylcarnitine accumulation in skeletal muscle may mediate this effect. Disclosure M. W. Schleh: None. B. J. Ryan: None. C. Ahn: None. A. Ludzki: None. P. Varshney: None. J. B. Gillen: None. J. F. Horowitz: None. Funding National Institutes of Health (R01DK077966, P30DK089503, T32DK007245, F32DK117522); Canadian Institutes of Health Research (DFS146190, 338735)
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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) | 0.003 | 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".