Hepatocyte Specific Shp1 Deletion and Low Dose Rosiglitazone Treatment Act in Concert to Improve Liver Glucose Homeostasis in Diet‐induced Obese Mice
Bibliographic record
Abstract
The protein‐tyrosine phosphatase Shp1 plays a key role in high‐fat diet (HFD)‐induced insulin resistance by negatively regulating insulin action on glucose homeostasis. Hepatocyte‐specific Shp1 knockout mice (Ptpn6 H‐KO ) on HFD show an improvement of hepatic insulin resistance and glucose homeostasis but also develop increased hepatic steatosis compared to their wild‐type littermates (Ptpn6 fl/fl ). Nevertheless, livers of Ptpn6 H‐KO mice on HFD have reduced hepatocellular damage and a reduced inflammatory profile alongside with increased peroxisome proliferator‐activated receptor gamma (PPARγ) activity, suggesting a new role for Shp1 in the regulation of PPARγ and the control of hepatic lipid metabolism. Therefore, the aim of the present study was to determine whether activation of PPARγ activity using rosiglitazone could further ameliorate hepatic glucose and lipid homeostasis as well as the inflammatory profile in Ptpn6 H‐KO mice. Male Ptpn6 H‐KO and Ptpn6 fl/fl mice were fed a HFD for 18 weeks. During the last 4 weeks the animals were treated with a very low dose of rosiglitazone (0.3 mg/kg/day). Low‐dose rosiglitazone treatment did not affect total body or adipose tissue weight, plasma levels of adiponectin or expression of PPARγ target genes in adipose tissue whereas PPARγ target genes expression was highly increased in liver. However, liver weight and liver triglycerides were increased in both rosiglitazone treated groups while plasma triglycerides were reduced by rosiglitazone. Furthermore, treatment with rosiglitazone led to an improvement in whole‐body glucose homeostasis and hepatic Akt activation both of which were even more ameliorated in HFD‐fed Ptpn6 H‐KO compared to Ptpn6 fl/fl mice. These results show that a low‐dose rosiglitazone treatment selectively target liver metabolism without detectable effects on adipose tissue, and our data further suggest that hepatic invalidation of Shp1 acts in concert with rosiglitazone to improve glucose metabolism in liver of HFD‐fed obese mice. Support or Funding Information CIHR This abstract is from the Experimental Biology 2018 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) | 0.001 | 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".