Obesity, Body Fat Distribution, and Circulating Glutamate Concentrations, A BI-Directional Mendelian Randomization Study
Bibliographic record
Abstract
Abstract Background: Various observational studies have reported that circulating levels of the amino acid glutamate was significantly associated with central fat accumulation in men and women. This is the case in the Framingham Heart Study Generation 3 for waist circumference, in the TwinsUK cohort for trunk fat and in a cohort of 1449 Japanese for visceral adipose tissue area measured by computed tomography. However, whether the association between abdominal adiposity and circulating glutamate is causal, as well as the direction of this association, is unknown. Here, we aimed to determine whether obesity and abdominal obesity were causally associated with circulating glutamate levels. Methods: We used a two-sample bi-directional inverse-variance weighted Mendelian randomization study design (IVW-MR). We derived summary statistics for our exposures and outcomes from published genome-wide association studies from the GIANT consortium (n = 681 275) and blood metabolites (n = 7 804). We identified independent genetic variants (r2 < 0.1) associated with body mass index (BMI) and waist-to-hip ratio adjusted for BMI (WHRadjBMI, p < 5x10-8) as well as circulating glutamate (p < 5x10-5). Results: We found no causal association between circulating glutamate levels and BMI (beta = 0.082, SE = 0.0413, p = 0.0471) or WHRadjBMI (beta = -0.00106, SE = 0.0401, p = 0.979). However, there was a positive effect of BMI (beta = 0.0608, SE = 0.0150, p = 5.19x10-5) and WHRadjBMI (beta = 0.0701, SE = 0.0198, p = 3.98x10-4) on circulating glutamate level. Conclusion: This Mendelian randomization analysis suggests that obesity and abdominal obesity are causally related to elevated circulating glutamate levels. Glutamate levels are not causally related to adiposity. Whether the downregulation of branched-chain amino acid catabolism in adipose tissue reported in obesity underlies this association should be explored.
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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 | 0.023 | 0.030 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.001 | 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".