Prohibitin has sex dimorphic role in adipose and immune functions
Bibliographic record
Abstract
The promoter of a gene that is selectively expressed in just a few cell types provides unique opportunities to study the pleiotropic function of a protein in two different cell types including the cell compartment specific function. This is not possible with a ubiquitous or a highly specific gene promoter. The adipocyte protein‐2 ( aP2 ) is one such gene. It is primarily expressed in adipocytes, but also selectively in monocytic macrophages and dendritic cells among various immune cell types. Thus, the aP2 gene promoter provides an opportunity to simultaneously manipulate adipose and immune functions in a transgenic animal model. Prohibitin (PHB) is a pleiotropic protein with cell compartment specific functions such as mitochondria and the plasma membrane. New evidence suggests that PHB has roles in adipocyte and immune cells. To discern the cell compartment specific functions of PHB in adipocyte and immune cell, we developed two novel transgenic mice by expressing wild type PHB and a phospho mutant PHB (Y114F or m‐PHB) from the aP2 gene promoter, separately. Both transgenic mice develop obesity in a sex‐neutral manner suggesting that m‐PHB retains mitochondria‐related adipogenic function. However, both transgenic mice develop obesity‐related metabolic dysregulation in a male sex‐specific manner. Interestingly, the male PHB mice spontaneously developed T2D and liver cancer, whereas the male m‐PHB mice developed lymph node tumors, or T1D in a context‐dependent manner. This would imply that plasma membrane‐related phosphorylation of PHB at Tyr‐114 has a role in immune cell functions. Collectively, our data suggests that PHB has sex dimorphic roles in adipose and immune functions, which are mediated in a cell compartment specific manner. Also, we provide evidence that sex differences in adipose and immune functions contribute to sex differences in diabetes and cancer, which warrant further investigations. Support or Funding Information SM is supported by funds from Natural Sciences and Engineering Research Council of Canada (NSERC) and Research Manitoba.
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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) | 0.002 | 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".