Time-optimized feeding is beneficial without enforced fasting

This is the final version. Available from The Royal Society via the DOI in this record.The authors declare that all the data that support the findings of this study are available within the paper (and its electronic supplementary material information files). All data are available in the main text or the electronic supplementary material.Time-restricted feeding (TRF) studies underscore that when food is consumed during the daily cycle is important for weight gain/loss because the circadian clock rhythmically modulates metabolism. However, the interpretation of previous TRF studies has been confounded by study designs that introduced an extended period of enforced fasting. We introduce a novel time-optimized feeding (TOF) regimen that disentangles the effects of phase-dependent feeding from the effects of enforced fasting in mice, as well as providing a laboratory feeding protocol that more closely reflects the eating patterns of humans who usually have 24 hour access to food. Moreover, we test whether a sudden switch from ad libitum food access to TRF evokes a corticosterone (stress) response. Our data indicate that the timing of high-fat feeding under TOF allows most of the benefit of TRF without obligatory fasting or evoking a stress response. This benefit occurs through stable temporal coupling of carbohydrate/lipid oxidation with feeding. These results highlight that timing the ingestion of calorically dense foods to optimized daily phases will enhance lipid oxidation and thereby limit fat accumulation.National Institute of Neurological Disorders and StrokeNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institute of Diabetes and Digestive and Kidney DiseasesNCR