Molecular-Level Dysregulation of Insulin Pathways and Inflammatory Processes in Peripheral Blood Mononuclear Cells by Circadian Misalignment

Apr 15, 2024Journal of proteome research

Disruption of Insulin and Inflammation Processes in Blood Cells Linked to Body Clock Misalignment

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Abstract

Circadian misalignment due to night work is associated with notable changes in protein and metabolite levels.

Proteins related to insulin regulation and inflammation exhibited significantly different patterns after a simulated night shift compared to a day shift.
Integration of protein and metabolite profiles revealed important connections between circadian disruption and metabolic disease risk.
Endogenous levels of glucose and insulin showed variations between the simulated night and day shift conditions.
Circadian misalignment may create conflicting signals between central and peripheral mechanisms that regulate insulin, potentially leading to chronic health issues like diabetes and obesity.

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Circadian misalignment due to night work has been associated with an elevated risk for chronic diseases. We investigated the effects of circadian misalignment using shotgun protein profiling of peripheral blood mononuclear cells taken from healthy humans during a constant routine protocol, which was conducted immediately after participants had been subjected to a 3-day simulated night shift schedule or a 3-day simulated day shift schedule. By comparing proteomic profiles between the simulated shift conditions, we identified proteins and pathways that are associated with the effects of circadian misalignment and observed that insulin regulation pathways and inflammation-related proteins displayed markedly different temporal patterns after simulated night shift. Further, by integrating the proteomic profiles with previously assessed metabolomic profiles in a network-based approach, we found key associations between circadian dysregulation of protein-level pathways and metabolites of interest in the context of chronic metabolic diseases. Endogenous circadian rhythms in circulating glucose and insulin differed between the simulated shift conditions. Overall, our results suggest that circadian misalignment is associated with a tug of war between central clock mechanisms controlling insulin secretion and peripheral clock mechanisms regulating insulin sensitivity, which may lead to adverse long-term outcomes such as diabetes and obesity. Our study provides a molecular-level mechanism linking circadian misalignment and adverse long-term health consequences of night work.

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Molecular-Level Dysregulation of Insulin Pathways and Inflammatory Processes in Peripheral Blood Mononuclear Cells by Circadian Misalignment

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