Pannexin 1 and Pannexin 3 regulate body fat accumulation in mouse models of dietinduced obesity
Bibliographic record
Abstract
Pannexins (Panx) are channel‐forming glycoproteins important in paracrine signaling and cellular development. Panx1 and Panx3 are expressed in adipocytes and adipose stromal cells. We discovered that mice globally lacking Panx1 (KO) have significantly greater total fat mass and reduced lean mass compared to wild type (WT) mice under a normal diet, while Panx3 KO mice have reduced total fat mass and weigh less than WT controls. Despite having higher fat content, Panx1 KO mice on a high fat diet exhibited no differences in weight gain but showed an increase in glucose and insulin levels compared to WT. However, metabolic cage data revealed that these Panx1 KO mice display significantly increased activity levels, higher ambulatory activity, and reduced sleep duration relative to their WT littermates on a high‐fat diet. To uncover the cellular mechanism responsible for the increased fat content in the Panx1 KO, we isolated primary cultures of adipose‐derived stromal cells (ASCs) from WT and KO fat pads. In WT ASCs we observed that Panx1 protein levels increase upon induction into an adipogenic lineage. ASCs isolated from Panx1 KO mice proliferate less but demonstrate enhanced adipogenic differentiation with increased intracellular lipid accumulation, glycerol‐3‐phosphate dehydrogenase (GPDH) enzyme activity, and adipokine secretion, as compared to WT ASCs. This was consistent with the increased adipocyte size (hypertrophy) and decreased adipocyte numbers observed in subcutaneous fat of the Panx1 KO mice compared to WT. Panx3 is also expressed in adipose stromal cells and Panx3 protein levels significantly increase in differentiated adipocytes. However, the effect of the Panx3 KO seems to be the opposite of the Panx1 KO, with decreased weight under a high fat diet and lower fat mass (even under a normal chow diet). We propose that Panx1 and Panx3 may play opposing roles in adipose stromal cells during the early stages of adipogenic proliferation and differentiation, regulating fat accumulation in vivo . Support or Funding Information Funded by the Canadian Institutes of Health Research (CIHR) grants to SP and LF 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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| 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".