The Monocrotaline Model of Hypertension Leads to Cachexia in Male but Not Female Mice
Notice bibliographique
Résumé
BACKGROUND: The monocrotaline (MCT) model of cardiac cachexia is a pharmaceutical approach to pulmonary hypertension that has been used to study heart failure and muscle wasting in rodents; however, little is known of how this pyrrolizidine alkaloid leads to peripheral changes in organ function and body mass, and sex differences have not been adequately compared. METHODS: Ten- to 12-week-old male and female C57BL/6N mice were treated weekly with MCT (200 mg/kg) for 8 weeks. Body weight, feeding behaviour and stool output were monitored weekly. In the final week, endurance was measured via a treadmill fatigue study. Upon termination, organs were weighed and processed for histochemistry and downstream gene expression analysis. RESULTS: Males were more susceptible to MCT-induced weight loss. No change in gross heart or skeletal muscle mass was observed in either sex, though lung mass was elevated in both sexes and cardiomyocyte size was larger in males (p < 0.05). MCT reduced the cross-sectional area of the tibialis anterior muscle in both sexes (p < 0.05), but this did not correspond to changes in endurance, as the treadmill fatigue study revealed no change in total time or distance run in response to MCT in either sex. RNA-seq analysis of the gastrocnemius muscle showed no significant changes in gene expression when compared within either the male or female cohort (n = 3), but when pooled (n = 6), MCT reduced gene pathways associated with mitochondrial function, adipogenesis and DNA repair and upregulated pathways associated with inflammation. Total fat mass was reduced by 40% in male mice in response to MCT, mainly because of significant reductions in inguinal white and brown interscapular adipose tissue mass. This was independent of food intake and intestinal distress, as no differences in stool wet:dry output or feeding behaviours were observed in either sex. Gene expression and immunohistochemical analysis of inguinal fat suggest that adipose tissue within males is particularly sensitive to MCT, as Tnfa, Ppargc1a and Zfp516 were upregulated, and there was a significant interaction between sex and MCT on Retn and Pnpl2a (aka Atgl) expression. CONCLUSIONS: These data suggest sex-dependent physiological responses of mice to MCT, where adipose tissue loss is more pronounced in males as a result of adipose tissue inflammation and metabolic activation. In contrast, conserved atrophic effects of MCT are observed within skeletal muscle, irrespective of sex. Further research using this model should consider sex-dependent responses.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
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 | 0,001 | 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 | 0,000 | 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 ».