45 Unravelling the Unique Burn-induced Temporal Alterations in Adipose Tissue Metabolism
Notice bibliographique
Résumé
Abstract Introduction A severe burn elicits a systemic hypermetabolic response that substantially alters the function of multiple organs and contributes to increased morbidity and mortality. A consequence of hypermetabolism is the activation of UCP1-mediated browning of white adipose tissue (WAT), which may further facilitate the hypermetabolic response. In this study, we aimed to provide comprehensive characterization of the acute and long term pathophysiological responses to burns to determine the persistence of adipose tissue browning and its potential contribution to the hypermetabolic response. Methods Mice were subjected to either a 30% total body surface area (TBSA) scald burn or were denoted sham. Body weight and food intake were monitored throughout the duration of the study. Cohorts were sacrificed at 6hrs, 1, 3, 5, 7, 14, 30 and 60d post-burn and adipose tissue depots were harvested. Mitochondrial respiration, protein expression, and morphology in adipose tissues were assessed. Results Despite consuming considerably more food, the burn group lost significantly more weight throughout the duration of the study. We also detected increases in free fatty acids and interleukin-6, markers of whole-body lipolysis and inflammation, respectively. At the tissue level, eWAT mass significantly decreased over time, suggesting that this depot provides substrate to fuel the hypermetabolic response. This was further supported by a decrease in adipocyte area and an increase in lipolytic markers which remains significant up until 60d post-burn relative to sham. There were no significant difference in iWAT mass, however we detected significant increases in the protein content of UCP1, the master regulator of adipose tissue browning, as early as day 3 which persisted until day 60. This was corroborated by the presence of UCP1+ adipocytes. Conclusions Consistent with previous human studies, a burn injury elicits a dynamic response that cannot be simply characterized by a single timepoint. The alterations that occur in adipose tissue are depot-specific, time-dependent, and this notion likely extends to other metabolic tissues. Further, we demonstrate that in our 30% TBSA burn murine model, the effects of the hypermetabolic response persist for up to 60 days following initial injury. Applicability of Research to Practice Our data indicate the hypermetabolic response persists for up to 60 days, the equivalent of approximately 7 years in humans. This underscores the severity of adipose tissue browning and potentially provides an explanation as to how the hypermetabolic response persists even after the wound has healed. Moreover, providing a comprehensive map of the time-dependent changes in a murine model gives clinicians a better indication of the metabolic effects in a burn patient and will contribute to the development of effective, targeted treatments.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».