Sex‐Related Differential Gene Expression Underlies Distinct Responses of Adipose Endothelial Cells Under A High‐Fat Diet
Notice bibliographique
Résumé
Background Despite similar rates of obesity, the prevalence and severity of obesity‐related metabolic diseases is lower in females compared to males. This relates with better preserved function of the adipose tissue in females. Consistent with the importance of capillaries in maintaining tissue functions, insufficient vascularization in expanding adipose tissue leads to adipocyte dysfunction, inflammation and whole‐body metabolic disturbances. Previously, we reported that angiogenesis is higher in the perigonadal adipose tissue in female compared to male mice on a high‐fat diet, leading to a higher capillary density in female adipose. Endothelial cells line capillaries and coordinate different cellular processes involved in angiogenesis, allowing for the necessary vascular remodelling needed in adipose maintenance. We hypothesize that differential gene networks/pathways in the endothelial cells of females compared to males support the better angiogenic response in female adipose tissue. Methods Male and female (5‐7 weeks old; n=4/group) mice were fed a high‐fat diet (60% kcal fat) for 7 weeks. White adipose tissue was harvested and used for whole‐mount imaging and endothelial cell isolation. Adipose tissue was stained with lectin and imaged to determine the vascular density. RNA extracted from the isolated endothelial cells was analyzed by RNA‐sequencing. Transcripts were assessed for differentially expressed genes (DEGs). Gene ontologies and gene set enrichment analysis were used to identify patterns of gene expression. Results Adipose tissue showed greater vascularization in high fat ‐fed females with vascular areas 27.2 ± 2.2 and 21.0 ± 0.6 % field of view in females and males respectively. RNA‐sequencing led to identification of 1225 DEG between male and female endothelial cells (P<0.01). Ontology analyses of the DEGs showed that male endothelial cells expressed higher levels of genes enriched in inflammatory responses and immune processes including chemokine production, complement/coagulation and leukocyte adhesion. In contrast, female endothelial cells lacked an inflammatory signature. Instead, the genes that were higher in female endothelial cells were related to cellular dynamics, such as machinery regulating transcription, translation, DNA replication and axon guidance. Conclusion Adipose endothelial cells from male and female mice have a high number of DEGs that reflect differences in endothelial cell angiogenic phenotype as well as other unique profiles that may be relevant to adipose function. Upregulation of ontologies relating to cellular replication and protein synthesis in females supports the observation of a better angiogenic response in the female adipose tissue and implies that intrinsic differences in male and female endothelial cells contribute to this capacity.
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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 | 0,000 | 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) | 0,001 | 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 ».