Mealtime: A circadian disruptor and determinant of energy balance?

Circadian rhythms play a critical role in the physiological processes involved in energy metabolism and energy balance (EB). A large array of metabolic processes, including the expression of many energy-regulating endocrine hormones, display temporal rhythms that are driven by both the circadian clock and food intake. Mealtime has been shown to be a compelling zeitgeber in peripheral tissue rhythms. Inconsistent signalling to the periphery, because of mismatched input from the central clock vs time of eating, results in circadian disruption in which central and/or peripheral rhythms are asynchronously time shifted or their amplitudes reduced. A growing body of evidence supports the negative health effects of circadian disruption, with strong evidence in murine models that mealtime-induced circadian disruption results in various metabolic consequences, including energy imbalance and weight gain. Increased weight gain has been reported to occur even without differences in energy intake, indicating an effect of circadian disruption on energy expenditure. However, the translation of these findings to humans is not well established because the ability to undertake rigorously controlled dietary studies that explore the chronic effects on energy regulation is challenging. Establishing the neuroendocrine changes in response to both acute and chronic variations in mealtime, along with observations in populations with routinely abnormal mealtimes, may provide greater insight into underlying mechanisms that influence long-term weight management under different meal patterns. Human studies should explore mechanisms through relevant biomarkers; for example, cortisol, leptin, ghrelin and other energy-regulating neuroendocrine factors. Mistiming between aggregate hormonal signals, or between hormones with their receptors, may cause reduced signalling intensity and hormonal resistance. Understanding how mealtimes may impact on the coordination of endocrine factors is essential for untangling the complex regulation of EB. Here a review is provided on current evidence of the impacts of mealtime on energy metabolism and the underlying neuroendocrine mechanisms, with a specific focus on human research.