Interferon regulatory factor 4 dictates metabolic flexibility of fat versus muscle loss during repeated intermittent fasting
Notice bibliographique
Résumé
Interferon regulatory factor 4 (IRF4) is a transcription factor that regulates the proliferation, differentiation, and metabolism of immune cells, such as macrophages and T cells. Recently, IRF4 has been shown to regulate lipolysis in adipocytes and increases in visceral human adipose tissue and murine white adipose tissue during acute fasting. However, it was unknown how IRF4 influences metabolic responses to repeated intermittent fasting. We hypothesized that blunted lipolysis, caused by Irf4 deletion, would promote altered metabolic substrate selection, specifically amino acids from muscle as opposed to fatty acids and glycerol from fat, to maintain energy homeostasis during repeated fasting in mice. Littermate whole body and adipocyte specific Irf4 knockout mice were placed on a 45% kcal from fat diet and either left to consume food ad-libitum or put on a 5:2 repeated fasting protocol for 10 weeks, which consisted of two 24-hour fast periods on non-consecutive days of the week. Body composition measures, using MRI, showed that littermate wild type mice lost more body and fat mass compared to Irf4 knockout mice during the fasting protocol. In line with our hypothesis, Irf4 knockout mice lost significantly more lean mass compared to wild-type mice. In conjunction with our MRI data, the Irf4 knockout mice had lower hindlimb, tibialis anterior muscle mass along with higher gonadal and inguinal white adipose tissue mass after the fasting protocol compared to the wild type mice. Additionally, we found that adipocyte-specific deletion of Irf4 recapitulated these effects on muscle and fat mass during intermittent fasting. We then used metabolic cages to examine energy expenditure and fuel oxidation. Complementary to our previous data, adipocyte-specific Irf4 knockout mice had lower fatty acid oxidation and higher carbohydrate oxidation rates compared to the wild type mice. Since adipocyte-specific Irf4 knockout mice have blunted lipolysis and lower fatty acid oxidation rates, our data suggests that another metabolic fuel source, specifically muscle protein, is being used to maintain energy homeostasis during fasting. Collectively, our data highlights a novel metabolic role for IRF4 in mediating fasting-dependent changes in body composition, specifically the balance between fat and muscle mass during repeated intermittent fasting. CIHR, NSERC, CFI, and Diabetes Canada This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
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Prédiction distillée sur la base complète
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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) | 0,001 | 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 ».