Metformin increases tauroursodeoxycholic acid levels to improve insulin resistance in diet-induced obese mice
Bibliographic record
Abstract
Abstract Metformin is widely used to surmount insulin resistance (IR) and type 2 diabetes. Evidence indicates that metformin improves insulin resistance associated with gut microbiota, but the underlying mechanism remains unclear. In the present study, metformin effectively improved insulin sensitivity and alleviated liver inflammation and oxidative stress in high-fat diet (HFD)-fed mice. Metabolomics analysis showed that metformin increased tauroursodeoxycholic acid (TUDCA) levels both in intestinal content and liver by reducing the production and activity of bile salt hydrolase (BSH). We further found that TUDCA was able to antagonize with KEAP1 to prevent its binding to Nrf2 and activate Nrf2/ARE pathway, thereby reducing intracellular ROS and improving insulin signaling. Moreover, metformin increased the proportion of Akkermanisia muciniphlia in the HFD-fed mice, while in vitro growth curve test confirmed that it’s TUDCA, not metformin, promoted the proliferation of A. muciniphlia . Subsequently, TUDCA administration could effectively ameliorate insulin resistance, activate hepatic Nrf2/ARE pathways, and increase the abundance of intestinal A. muciniphlia in ob/ob mice. These findings reveal that metformin remodels the gut microbiota, reduces oxidative stress and enhances insulin sensitivity partly due to increasing the production of TUDCA. This provides a novel mechanism by which metformin alleviates diet-induced insulin resistance and improves metabolism.
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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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| 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".