Effects of Partial Knockout of Skeletal Muscle Dynamin-Related Protein 1 on Skeletal Muscle Characteristics in Lean and Obese Mice
Notice bibliographique
Résumé
Dynamin-related protein 1 (Drp1) is a key regulator of mitochondrial fission and plays an essential role in maintaining skeletal muscle homeostasis. Recent studies reported muscle atrophy in mice when skeletal muscle Drp1 content was reduced. However, whether such atrophic phenotype also exists in diet-induced obese mice remains unknown. We recently reported that reducing skeletal muscle Drp1 resulted in improved whole-body glucose homeostasis and insulin sensitivity in diet-induced obese mice, but not lean healthy mice, suggesting Drp1 may exert divergent effects on physiological phenotypes under different conditions. OBJECTIVE: To determine the effects of partial knockout of skeletal muscle-specific heterozygous Drp1 (mDrp1 +/− ) on body composition, energy expenditure and skeletal muscle physiology in lean and obese mice. HYPOTHESIS: mDrp1 +/− exhibits divergent alterations in physiological characteristics between lean healthy and obese mice. Methods: Tamoxifen-inducible mDrp1 +/− mouse model was generated. Nine-week-old male and female mDrp1 +/− and wildtype (WT) mice (n=6-8/group) were fed with either a high-fat diet (HFD) or low-fat diet (LFD) for four weeks, received tamoxifen injections, and remained on their respective diet for another four to six weeks. A DXA scan was conducted to measure body composition. Mice were housed in Promethion metabolic cages for 48 hours to measure energy expenditure. Isolated soleus (SOL) and extensor digitorum longus (EDL) muscles were used for assessing muscle cross sectional area (CSA) and contractility. Results: HFD-fed mice had significantly higher percentage of body fat ( p = 0.045) and lower respiratory exchange ratio ( p <0.0001) than LFD-fed mice, regardless of genotype. Regarding skeletal muscle characteristics, SOL from mDrp1 +/− mice exhibited larger CSA ( p = 0.052) than WT mice, regardless of diet. However, there were no differences in muscle force or fatigue resistance in SOL between groups. In contrast, EDL muscle isolated from mDrp1 +/− mice fed with HFD had greater muscle force than WT mice, but interestingly the force was lower in mDrp1 +/− /LFD mice than WT/LFD mice (genotype x diet interaction effect, p = 0.001). Consistently, a significant interaction was found in both twitch and tetanic rate of force development and relaxation rates (genotype x diet interaction effect, p = 0.022, p = 0.033, p = 0.040, and p = 0.020, respectively). There was no difference in EDL muscle CSA between groups. CONCLUSION: Our data suggests that partial knockout of Drp1 in skeletal muscle induced divergent effects on CSA, force production and fatigability between diet induced obese and lean healthy mice. This study was supported by the National Institute of Health (R15DK131512). This is the full abstract presented at the American Physiology Summit 2024 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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 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 tête enseignante, 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 ».