Loss of Intestinal Epithelial AMPK Does Not Alter Susceptibility to Acute Chemical Colitis or Bacterial Infection
Bibliographic record
Abstract
AMP‐Activated Protein Kinase (AMPK) is a master regulator of cellular energy status. Its primary actions are mediated by its alpha catalytic subunit, which has two isoforms. Previous evidence in mice has suggested that loss of an individual AMPK‐α isoform compromises critical functions of the intestinal epithelium such as tight junction permeability while intact AMPK activity is protective against mucosal inflammation. These processes are essential to maintain the intestinal barrier and prevent chronic inflammation. However, AMPK‐dependent effects under cellular stress conditions have not been consistent and appear context‐dependent. Additionally, published studies have not confirmed whether AMPK is necessary and sufficient for these effects. The goals of this study were to determine if AMPK is required to protect from mouse models of acute colitis. Methods Deletion of AMPKα specifically in intestinal epithelial cells was accomplished by crossing Prkaa1/2 floxed mice with Villin‐Cre mice. Dextran sulfate sodium (DSS) colitis was induced in conventionally housed intestinal epithelial cell‐specific AMPK knockout (AMPKα ΔIEC KO ) and AMPK floxed (AMPKα fl/fl ) mice. 40kDa DSS was administered at 2.5% in drinking water ad libitum for 5 days followed by 3 days of water. Disease activity index was calculated from daily measures of body weight, stool consistency, and presence of hemaoccult. On the day of sacrifice mice were orally gavaged with 4kDa FITC‐dextran and blood was collected after 4 hours to determine intestinal permeability. Mice were sacrificed and intestinal tissues were flash frozen. Citrobacter rodentium infection was performed in mice housed under specific pathogen‐free (SPF) conditions following overnight treatment of 50ng/mL streptomycin. Mice were orally gavaged with ~10 8 CFU of C. rodentium (DBS100 streptomycin‐resistant strain). Fecal bacterial load was determined regularly until sacrifice on day 10 post‐infection. Colon and extra‐intestinal tissues (mesenteric lymph nodes, spleen, and liver) were excised to determine bacterial burden. Results AMPKα ΔIEC KO mice did not exhibit increased susceptibility to 2.5% DSS compared to AMPKα fl/fl mice as determined by similar changes in body weight and disease activity index throughout the course of disease. In addition, there were no significant differences in colon weight or length after DSS (n = 4 – 15). AMPKα ΔIEC KO mice do not appear to have significantly increased intestinal permeability after DSS treatment. To test if AMPK is important for responses to enteric infection, mice were infected with Citrobacter rodentium , a mouse model of enteropathogenic (EPEC) and enterohemorrhagic E. coli (EHEC) infection in humans. Infected mice had identical increases in fecal bacterial burden over time (~10 7 CFU/g, n = 3–6) and loss of AMPK did not affect disease progression. In addition, AMPK deficiency did not increase bacterial invasion of extra‐intestinal tissues (n = 3–4). Conclusions These data suggest that AMPK plays only a minor role in intestinal epithelial function and suggests that protection from colitis is mediated by AMPK‐independent pathways. Support or Funding Information NIH 2R01DK091281 (DFM) This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| 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".