SUN-LB018 Role of BMAL1 in Western Diet-Induced Disruption of Circadian Hypothalamic Feeding Neuropeptides
Notice bibliographique
Résumé
Circadian rhythms drive the timing of daily physiological functions, including food intake. These cellular rhythms depend on the intricate regulation of core clock genes, such as BMAL1. Disruptions of the molecular clock in rodents have been shown to induce obesity and features of the metabolic syndrome, as well as altering diurnal food intake patterns. In vitro studies using palmitate, a saturated fatty acid comprising a large portion of high-fat diets, demonstrate alterations in hypothalamic BMAL1 and feeding-related neuropeptide expression. We hypothesized that the high-fat, high-sugar (Western) diet alters circadian food intake rhythms by altering hypothalamic feeding-related neuropeptide expression in a BMAL1-dependent manner. C57BL/6-J mice were fed either rodent chow (RC; control) or Western diet (WD) for 16 weeks. Male and female WD mice gained more weight compared to controls, and consumed a larger proportion of their food during the inactive (light) period. Hypothalamic mRNA expression patterns of neuropeptide Y (NPY), agouti-related peptide (AgRP), and proopiomelanocortin (POMC) were markedly altered by WD feeding. Compared to RC controls, WD mice showed a blunted mRNA expression of AgRP and NPY, accompanied by an altered hypothalamic expression of the clock genes BMAL1 and Per2. To identify the cellular mechanism by which the WD affects the central control of food intake, hypothalamic cell lines were derived from adult BMAL1-wildtype (WT) and knockout (KO) C57BL/6-J mice. Hypothalamic primary cultures were immortalized with SV40 T-antigen and characterized to demonstrate a robust rhythmic cycling of clock gene expression, in addition to the expression of several neuropeptides. Importantly, BMAL1-WT neurons exhibited a 24-hour period in Per2 clock gene mRNA expression, while the BMAL1-KO cell line lacked rhythmic expression of Per2, confirming the cell line as a hypothalamic model of circadian disruption. Additionally, the expression patterns of NPY, AgRP, and POMC were altered with BMAL1 knockout. Treatment with palmitate increased BMAL1, Per2, and POMC expression at 9 or 21 hours, corresponding to the peak and trough of clock and neuropeptide mRNA expression. Taken together, these results suggest a role for the circadian clock in regulating hypothalamic neuropeptide expression and, thereby, central control of food intake. Sources of research support: MNC has received graduate awards from the Banting and Best Diabetes Centre and the Ontario Graduate Scholarship; studies were supported by CIHR and NSERC operating grants. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.
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) | 0,000 | 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 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 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 ».