The French National Centre for Scientific Research


Interactions between cerebral clocks and food intake: temporal and metabolic aspects

Project leaders : Patrick Vuillez & Etienne Challet

Our team has demonstrated that metabolic factors modulate functioning of the master clock located in the suprachiasmatic nuclei of the hypothalamus (SCN). Among others, metabolic cues associated with a hypocaloric diet, independently of feeding time, can modify timing in the suprachiasmatic clock, and increase its circadian responses to light. Conversely, eating a hypercaloric diet slows the suprachiasmatic clock and reduces its circadian responses to light. To understand the metabolic feedback on suprachiasmatic cells, we assess on the one hand which peripheral signals (metabolic hormones and plasma metabolites) affect the master clock, and also their mechanisms of action in vivo and in vitro.
The ability to predict and anticipate mealtime is likely a key for survival in most animals. In response to daily limited access to food, animals express food-anticipatory activity, a behavior considered as an output of a network of food-entrainable cerebral clocks, called the “food clock”. Our pioneering work has revealed that the cerebellum contains a self-sustained clock belonging to the circadian network of the food clock, also involving the metabolic hypothalamus and brainstem. Regarding molecular mechanisms of the food clock, our recent work revealed that the circadian gene Rev-erbα is required for the food clock. Currently, we investigate which brain clocks control the daily feeding/fasting cycle and meal anticipation, and what are the chronomodulators linked to meal time that reset the food clock. The oscillating properties of the food-entrainable cerebral network are characterized in organotypic slices using in vitro bioluminescence recording


Members

Etienne Challet
 
Patrick Vuillez
 

Collaborations

Fabrice Bertile (IPHC, CNRS and Univ Strasbourg, F)
Khalid El Allali (Hassan II Agronomy & Veterinary Inst, MO)
Andries Kalsbeek (Univ Amsterdam, NL)
Chantal Mathis (LNCA, CNRS, Univ Strasbourg)
Ralph Mistlberger (Univ Burnaby, CA)
Marie-Pierre Moisan et Guillaume Ferreira (NutriNeuro, INRAE, CNRS, Univ Bordeaux)
Ute Rogner (Institut Cochin, Paris)

Funding

Fondation pour la Recherche Médicale (FRM)

Fédération pour la Recherche sur le Cerveau (FRC)



Selected publications

Challet E (2019). The circadian regulation of food intake. Nat Rev Endocrinol 15: 393-405.

Sen S, Dumont S, Sage-Ciocca D, Reibel S, de Goede P, Kalsbeek A, Challet E (2018). Expression of the clock gene Rev-erba in the brain controls the circadian organization of food intake and locomotor activity, but not daily variations of energy metabolism. J Neuroendocrinol 30: e12557.

Sen S, Raingard H, Dumont S, Kalsbeek A, Vuillez P, Challet E (2017). Ultradian feeding in mice not only affects the peripheral clock in the liver, but also the master clock in the brain. Chronobiol Int 34: 17-36.

Delezie J, Dumont S, Sandu C, Reibel S, Pevet P, Challet E (2016) Rev-erba in the brain is essential for circadian food entrainment. Sci Rep 6: 29386.

 


 
The French National Centre for Scientific Research