Regulation of AMPK and Hepatic Metabolism by Folic acid Supplementation in Non‐alcoholic Fatty Liver Disease
Bibliographic record
Abstract
Non‐alcoholic fatty liver disease (NAFLD) is a worldwide epidemic associated with obesity and type 2 diabetes. Chronic high‐fat diet consumption promotes NAFLD which is characterized by hepatic lipid accumulation, hyperglycemia and hyperlipidemia. Emerging evidence suggests that metabolic aberration during NAFLD may be related to dysregulation of AMP‐activated protein kinase (AMPK). AMPK is an endogenous energy sensor involved in regulating lipid and glucose metabolism, which has been proposed as a potential therapeutic target in NAFLD and its associated metabolic disorders. Folic acid is an essential B vitamin that has been implicated in NAFLD through improvement of liver function. The aim of our study was to investigate the mechanisms by which folic acid supplementation regulated hepatic AMPK and its impact on cholesterol and glucose metabolism. Male C57BL/6J mice were fed a control diet (10% kcals fat), a high‐fat diet (60% kcals fat) or a high‐fat diet supplemented with folic acid for 5 weeks. Mice fed a high‐fat diet exhibited fatty liver, hyperglycemia, elevated activity of hepatic HMG‐CoA reductase and lower AMPK activity. Folic acid supplementation restored AMPK activity, attenuated hepatic lipid accumulation and reduced blood glucose levels. Activation of AMPK by folic acid was mediated, in part, through activation of its upstream kinase LKB1. Folic acid‐induced AMPK activation could attenuate HMG‐CoA reductase activity via AMPK‐dependent phosphorylation of the reductase and hence reduce hepatic cholesterol biosynthesis. Our results suggest that folic acid supplementation can improve cholesterol and glucose metabolism through restoration of AMPK activation in the liver, which may have a therapeutic implication in mitigating hepatic lipid accumulation and hyperglycemia in NAFLD. Support or Funding Information This study was supported, in part, by Natural Sciences & Engineering Research Council of Canada and St. Boniface Hospital Research Centre.
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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 | 0.000 |
| 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) | 0.001 | 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".