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The circadian regulation of food intake

Abstract

Feeding, which is essential for all animals, is regulated by homeostatic mechanisms. In addition, food consumption is temporally coordinated by the brain over the circadian (~24 h) cycle. A network of circadian clocks set daily windows during which food consumption can occur. These daily windows mostly overlap with the active phase. Brain clocks that ensure the circadian control of food intake include a master light-entrainable clock in the suprachiasmatic nuclei of the hypothalamus and secondary clocks in hypothalamic and brainstem regions. Metabolic hormones, circulating nutrients and visceral neural inputs transmit rhythmic cues that permit (via close and reciprocal molecular interactions that link metabolic processes and circadian clockwork) brain and peripheral organs to be synchronized to feeding time. As a consequence of these complex interactions, growing evidence shows that chronodisruption and mistimed eating have deleterious effects on metabolic health. Conversely, eating, even eating an unbalanced diet, during the normal active phase reduces metabolic disturbances. Therefore, in addition to energy intake and dietary composition, appropriately timed meal patterns are critical to prevent circadian desynchronization and limit metabolic risks. This Review provides insight into the dual modulation of food intake by homeostatic and circadian processes, describes the mechanisms regulating feeding time and highlights the beneficial effects of correctly timed eating, as opposed to the negative metabolic consequences of mistimed eating.

Key points

  • Short-term food consumption is regulated by a balance between orexigenic and anorexigenic factors.

  • Daily pattern of eating is controlled by circadian clocks, including the master clock in the suprachiasmatic nuclei reset by ambient light and other brain clocks reset by feeding time, via hormonal, nutrient and visceral cues.

  • Circadian desynchronization — owing to mistimed eating or chronodisruption — has deleterious consequences on metabolic health.

  • Timed dietary patterns may help to prevent circadian desynchronization and reduce metabolic disorders.

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Fig. 1: Circadian control of the daily feeding–fasting cycle by brain clocks.
Fig. 2: Reciprocal interactions between the circadian clocks and metabolism at cellular and systemic levels.
Fig. 3: Synchronization of food-entrainable clocks by metabolic hormones.

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Nature Reviews Endocrinology thanks H. Piggins, R. Mistlberger and F. Scheer for their contribution to the peer review of this work.

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Glossary

Secondary clocks

Circadian clocks found in brain structures outside of the suprachiasmatic nuclei and in peripheral organs. Self-sustained rhythmicity of extra-suprachiasmatic clocks and their cellular coupling are less robust, which might confer more flexibility to resetting cues, than the more rigid, master suprachiasmatic clock. The majority of the secondary clocks can be shifted by timed feeding (see the glossary entry for ‘Food-entrainable clocks’).

Free-running conditions

Housing conditions without external time cues, such as constant light or dark or constant temperature, that allow for the detection of the endogenous nature of circadian rhythms.

Clock genes

Specific genes involved in the molecular clock machinery.

Daily rhythm

A 24 h rhythm expressed under a light–dark cycle that is not necessarily endogenous.

Phase-shift

Change in phase of a circadian clock (or its readout, a circadian rhythm).

Food-entrainable clocks

Secondary clocks in the brain and peripheral tissues that can be phase-shifted by timed feeding.

Synchronizing factors

Sometimes called zeitgebers or time-givers; temporal signals, such as light or feeding time, that are able to reset circadian clocks, that is, to adjust their phase.

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Challet, E. The circadian regulation of food intake. Nat Rev Endocrinol 15, 393–405 (2019). https://doi.org/10.1038/s41574-019-0210-x

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