Abstract 010: Adipocyte-derived Aldosterone And Cortisol Are Nox1/4 Dependent: Implications In Obesity-associated Vascular Dysfunction.
Notice bibliographique
Résumé
We previously demonstrated that aldosterone (aldo) is produced by adipocytes, an effect associated with reactive oxygen species (ROS) production and adipokine production, which influences vascular function. These processes are exaggerated in obesity. Whether ROS themselves play a role in adipocyte-derived aldo is unclear. Studies were performed in db/m (lean) and db/db (obese) mice, treated with low (20mg/kg/day) or high dose (60mg/kg/day) GKT137831 (GKT, Nox1/4 inhibitor, 16 weeks). Epididymal (EVAT) and perivascular (PVAT) fat were collected. Human adipocytes (SW872) were also studied. Aldo and corticosterone levels were measured by ELISA. Gene expression was assessed by qPCR. ROS generation was assessed by chemiluminescence and amplex red. Plasma aldo levels in db/db (pg/mL: 518 vs. 272g) and aldo levels in culture media from db/db adipocytes were increased (pg/mL/μg RNA: 1964 vs. 388), p<0.05. All effects were decreased by high dose GKT. In PVAT, CYP11B2 gene expression was increased in db/db (2.6±0.8 vs control 1.1±0.1, p<0.05), an effect blocked by Nox1/4 inhibition. Corticosterone levels in culture media from db/db adipocytes were also increased. Gene expression of adipocyte differentiation marker, AP2, was increased (3.5±1.1 vs control 1.4±0.4) in obese mice. GKT decreased AP2 levels. In human adipocytes, AngII stimulation increased aldo (6 fold) and cortisol (4 fold) production, as well as superoxide (1 fold) and H2O2 (2 fold) levels (p<0.05 vs vehicle). Increased levels of superoxide by Ang II were blocked by GKT and ML171 (Nox1 inhibitor); while Ang II-induced H2O2 production was inhibited only by GKT. Ang II-induced aldo production was blocked by tempol (SOD mimetic), GKT and ML171. In contrast, cortisol was only blocked by tempol and GKT. In conclusion, aldo production in adipocytes is dependent on ROS formation and involves Nox1 and Nox4. Nox4 also influences adipocyte-derived cortisol. These data suggest that Nox1/4 may play a role in adipocyte-derived aldosterone and cortisol production, effects that are amplified in obesity. Our findings suggest that adipocyte Nox1/4 may be a putative therapeutic target in obesity-associated hyperaldosteronism and cardiovascular damage.
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 | 0,000 | 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 | 0,000 | 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 ».