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Significance Circadian misalignment (i.e., behavioral processes such as food intake or sleep occurring at inappropriate endogenous circadian times) commonly occurs during shift work and is associated with health problems. Identifying mechanisms underlying health problems associated with circadian misalignment will help develop precision medicine countermeasures. Thus, we investigated the impact of circadian misalignment on the human plasma proteome using a simulated nightshift protocol in healthy volunteers. We demonstrate that circadian and/or behavioral wake–sleep/food intake–fasting cycles regulate 24-h time-of-day patterns of the human plasma proteome. Further, we show that proteins altered during circadian misalignment are associated with biological pathways involved in immune function, metabolism, and cancer and with altered glucose and energy metabolism, identifying potential mechanisms contributing to metabolic dysregulation.

Mistimed food intake and sleep alters 24-hour time-of-day patterns of the human plasma proteome