Ghrelin Blunts Adrenergic‐Stimulated Lipolysis in Subcutaneous and Visceral Adipose Tissue Ex Vivo, but not In Vivo
Notice bibliographique
Résumé
Introduction Ghrelin is an appetite and growth hormone (GH) ‐stimulating gastric hormone. Ghrelin rises preprandially and immediately declines to baseline after meal consumption. Therefore, it is important to elucidate any potential role that ghrelin may have in mediating substrate metabolism surrounding entrained meal time. There is evidence to suggest that ghrelin may inhibit the adrenergic stimulation of lipolysis in isolated adipocytes, which would seem intuitive if we consider ghrelin as a meal‐priming signal, as there is unlikely to be a requirement to spare blood glucose following a meal. However, upon administration of ghrelin in humans, there are marked increases in local adipose and skeletal muscle rates of glycerol appearance, indicative of increased lipolysis. In vivo findings, though, are confounded by a secondary increase in GH, which may be lipolytic. Previously, using an ex vivo (adipose tissue organ culture) model, we have shown that both acylated (AG) and unacylated (UnAG) ghrelin blunt adrenergic (CL 316 243) stimulated lipolysis, with a corresponding reduction in the activation of hormone‐sensitive lipase (HSL). Our current experimental model is aimed at elucidating whether or not this newly found, direct role for ghrelin in mediating adipose tissue lipolysis can be replicated in vivo. Methods To date, subcutaneous iWAT and visceral RP adipose tissue depots have been harvested from healthy, male Sprague‐Dawley rats for the assessment of glycerol release following injection with either saline, CL (1mg/kg), CL + AG and CL + UnAG (50μg/kg). In vivo tissue and blood collection was done 30min following IP injection. Western blots were used to quantify the activation of markers associated with lipolysis. qPCR will be undertaken to assess markers of fatty acid storage (eg. fatty acid synthase). ELISA will be used to quantify GH, insulin and glucagon as potential circulating confounders. Results Ex vivo, AG and UnAG blunted CL‐stimulated lipolysis, but did not independently affect glycerol release or lipolytic signalling proteins (p>0.05) and were not pursued further with in vivo injection studies. When compared to saline (0.36 ± 0.06 mM), CL injection markedly increased the rates of glycerol release (0.77 ± 0.07 mM; p<0.05). There was no effect of co‐administration of CL with ghrelin isoforms on the CL‐mediated increase in glycerol release (AG: 0.77 ± 0.04; UnAG: 0.79 ± 0.04 mM). These outcomes were mirrored by signalling proteins, in that HSL (Serine 563/660 ) activation was significantly elevated with CL (iWAT: 2.80 ± 0.43; RP: 4.69 ± 1.23) compared to saline injection (iWAT: 0.78 ± 0.23; RP: 2.13 ± 1.03) and unchanged with the co‐injection ghrelin (iWAT ‐ CL+AG: 2.61 ± 0.54, CL+UnAG: 2.39 ± 0.22; RP – CL+AG: 6.83 ± 1.89, CL+UnAG: 11.66 ± 2.93). Conclusions We extend on previous findings and show that ghrelin directly inhibits adrenergic‐stimulated lipolysis in subcutaneous and visceral adipose depots. However, in the living animal, these actions appear to be confounded by other factors. Transcriptional markers of lipid storage will be used to elucidate whether ghrelin is also acting directly as a storage signal, beyond its inhibition of fatty acid mobilization. These experiments will be seminal in contributing to the interpretation of AG and UnAG's effects in adipose tissue lipid metabolism. Support or Funding Information Funded by NSERC This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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 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) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,001 |
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 ».