Titre :

A Mathematical Model of the Liver Circadian Clock Linking Feeding and Fasting Cycles to Clock Function

Auteur(s) :

Woller, Aurore [Auteur]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Laboratoire de Physique des Lasers, Atomes et Molécules - UMR 8523 [PhLAM]
Duez, Helene [Auteur]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Staels, Bart [Auteur]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Lefranc, Marc [Auteur]
Laboratoire de Physique des Lasers, Atomes et Molécules - UMR 8523 [PhLAM]

Titre de la revue :

Cell Reports

Pagination :

1087-1097

Éditeur :

Elsevier Inc

Date de publication :

2016-10

ISSN :

2211-1247

Mot(s)-clé(s) en anglais :

mammalian circadian clock
metabolism
mathematical model
SIRT1
AMPK
NAMPT
NAD+
REV-ERB
metabolic disorders

Discipline(s) HAL :

Sciences du Vivant [q-bio]/Bio-Informatique, Biologie Systémique [q-bio.QM]

Résumé en anglais : [en]

To maintain energy homeostasis despite variable energy supply and consumption along the diurnal cycle, the liver relies on a circadian clock synchronized to food timing. Perturbed feeding/fasting cycles have been associated ...
Lire la suite >To maintain energy homeostasis despite variable energy supply and consumption along the diurnal cycle, the liver relies on a circadian clock synchronized to food timing. Perturbed feeding/fasting cycles have been associated with clock disruption and metabolic diseases, however the mechanisms are unclear. To address this question, we have constructed a mathematical model of the mammalian circadian clock incorporating the metabolic sensors SIRT1 and AMPK. The clock response to various temporal patterns of AMPK activation was simulated numerically, mimicking the effects of a normal diet, fasting and a high-fat diet. The model reproduces the dampened clock gene expression and NAD+ rhythms reported for mice on a high-fat diet, and predicts that this effect may be pharmacologically rescued by timed REV-ERB agonist administration. Our model thus identifies altered AMPK signaling as a mechanism leading to clock disruption and its associated metabolic effects, and a pharmacological approach to reset the clock in obesity.Lire moins >

Langue :

Anglais

Comité de lecture :

Oui

Audience :

Internationale

Vulgarisation :

Non

Projet ANR :

Centre Européen pour les Mathématiques, la Physique et leurs Interactions

Collections :

• Laboratoire de Physique des Lasers, Atomes et Molécules (PhLAM) - UMR 8523

Source :

Harvested from HAL