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

McDermott, Jason E.; Jacobs, Jon M.; Merrill, Nathaniel J.; Mitchell, Hugh D.; Arshad, Osama A.; McClure, Ryan; Teeguarden, Justin; Gajula, Rajendra P.; Porter, Kenneth I.; Satterfield, Brieann C.; Lundholm, Kirsie R.; Skene, Debra J.; Gaddameedhi, Shobhan; Van Dongen, Hans P. A.

doi:10.1021/acs.jproteome.3c00418

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

Journal Article · Mon Apr 15 04:00:00 UTC 2024 · Journal of Proteome Research

DOI: https://doi.org/10.1021/acs.jproteome.3c00418 · OSTI ID:2478152

^[1]; Jacobs, Jon M. ^[2]; Merrill, Nathaniel J. ^[2]; Mitchell, Hugh D. ^[2]; Arshad, Osama A. ^[2]; McClure, Ryan ^[2]; Teeguarden, Justin ^[2]; Gajula, Rajendra P. ^[3]; Porter, Kenneth I. ^[3]; Satterfield, Brieann C. ^[3];

^[3]; Skene, Debra J. ^[4]; Gaddameedhi, Shobhan ^[5]; Van Dongen, Hans P. A. ^[3]

Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Oregon Health & Science Univ., Portland, OR (United States)
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
Washington State Univ., Spokane, WA (United States)
Univ. of Surrey, Guildford (United Kingdom)
North Carolina State University, Raleigh, NC (United States)

Circadian misalignment due to night work has been associated with elevated risk for chronic diseases. Here, 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. 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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Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER); USDOE Laboratory Directed Research and Development (LDRD) Program; US Army Research Office (ARO); National Institutes of Health (NIH); Center for Human Health and the Environment (CHHE); Biotechnology and Biological Sciences Research Council (BBSRC); European Union (EU)

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 2478152

Report Number(s):: PNNL-SA--186735

Journal Information:: Journal of Proteome Research, Journal Name: Journal of Proteome Research Journal Issue: 5 Vol. 23; ISSN 1535-3893

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
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sleep

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

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