SAT-583 Assessment of Thermoregulatory Pathways Induced in Male and Female Mice Lacking Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) in Response to Cold Acclimation
Bibliographic record
Abstract
Abstract Pituitary Adenylate Cyclase Activating Polypetptide (PACAP) is a peptide hormone known to regulate energy homeostasis1. Mice lacking PACAP are cold sensitive and have impaired adrenergic-induced thermogenesis2-4. Interestingly, Pacap null mice can survive cold housing if acclimated slowly, similar to what was observed in UCP1 deficient mice4,5. We hypothesized that Pacap-/- mice employ alternate thermogenic pathways to compensate for impaired adaptive thermogenesis and assessed shivering thermogenesis and UCP1-dependent and UCP1-independent adaptive thermogenesis in male and female Pacap-/- and Pacap+/+ with cold acclimation (4°C). Assessment of oxidative fibres in skeletal muscles and behavioural observations did not show evidence of prolonged shivering in male or female Pacap-/- mice during cold acclimation compared to Pacap+/+ mice. We did however observe morphological and molecular differences in adipose tissues of Pacap-/- mice compared to Pacap+/+ mice that were distinct in males and females. Cold-acclimated, female Pacap-/- mice had decreased induction of UCP1 protein in intrascapular brown fat (iBAT), yet had a significantly higher beiging and UCP1 immunoreactivity (ir) in gonadal white fat (gWAT) compared to female Pacap+/+ mice. Furthermore, beiging was observed in inguinal white fat (ingWAT) and gWAT of female Pacap-/- mice housed at thermoneutrality (30°C), a finding not observed in Pacap+/+ control mice. Unlike female mice, we did not observe impaired UCP1 induction in iBAT of male Pacap-/- mice compared to Pacap+/+ mice, and this was associated with negligible UCP1-ir in male gWAT similar to wildtype controls. Despite previous work that has established impaired adaptive thermogenesis in Pacap-/- mice4, we show here that UCP1 protein can be induced in adipose tissues of Pacap-/- mice during cold acclimation, although to a lesser degree or in a different pattern compared to Pacap+/+ control mice. Taken together, this work suggests that while PACAP is clearly involved in regulating thermoregulation, it is not required for cold-induced UCP1 expression. In addition, this work highlights sexual dimorphism in adipose tissue remodeling and induction of thermogenesis with cold acclimation. References: (1) Rudecki AP, et al. Trends Endocrinol Metab. 2016;27(9), 620–632. (2) Gray SL, et al. J Mol Endocrinol. 2001;15(10), 1739–1747. (3) Gray SL, et al. J Endocrinol. 2002;143(10), 3946–3954. (4) Diané A, et al. J Endocrinol. 2014;222, 327–339. (5) Golozoubova V, et al. FASEB J. 2001;15, 2048–2050.
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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 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| 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) | 0.007 | 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".