Investigating the effects of thermoneutral housing on skeletal and cardiac muscle function in D2 mdx mice
Notice bibliographique
Résumé
Since its discovery, the mdx mouse has been the foundation for research on Duchenne muscular dystrophy (DMD) and its potential therapies. Although, nearly all studies using mdx mice as an experimental model have been conducted under “standard” lab conditions using room (22C) instead of thermoneutral (TN, 30C) temperature housing. Room temperature (RT) is a mild cold stress to mice, causing metabolic adaptations that can confound experimental results, limiting their interpretation and translation to humans. This study investigated the effects of housing temperature on whole-body metabolism and skeletal and cardiac muscle function in the mdx mouse. To this end, 20 D2 mdx mice (age 5 weeks, n = 10 per group) were housed at RT and TN for 10 weeks. Metabolic cage analysis demonstrated that TN housed mdx mice displayed significantly decreased VO2 consumption and reduced food intake that was likely due to lowered daily energy expenditure. TN housed mice also had significantly lower respiratory exchange ratio values, indicative of increased fat metabolism. However, there were no differences in body mass or composition (i.e., % lean and fat mass). Treadmill-to-fatigue experiments revealed no differences in exercise performance. Furthermore, ex vivo muscle contractility analysis displayed no differences in extensor digitorum longus or soleus specific force generation between TN and RT housed mice. Analysis of cardiac structure/function demonstrated that TN housed mdx mice exhibited a reduction in cardiac output, which we attributed to diastolic dysfunction. While ejection fraction and fractional shortening were not different among the two groups, TN housing led to a significant reduction in end diastolic volume (EDV) and left ventricle internal diameter (diastole, LVID;d), as well as increased relative wall thickness (diastole, RWT;d) compared to RT housed mice. Though isovolumic relaxation time was prolonged in TN-housed mice, this did not reach statistical significance. Taken together, our results demonstrate that TN housing had minimal effects on skeletal muscle contractility, but did lead to signs of diastolic dysfunction in young mdx mice. Future studies will examine the effects of TN housing in aged mdx mice, when systolic dysfunction occurs, as well as any influence of TN housing on the efficacy of potential muscle wasting therapeutics. Overall, our results support the growing literature that highlights the importance of selecting the appropriate housing temperature when studying metabolism or muscle wasting conditions in mice. NSERC This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
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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 | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,002 |
| 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 ».