Molecular-Level Dysregulation of Insulin Pathways and Inflammatory Processes in Peripheral Blood Mononuclear Cells by Circadian MisalignmentClick to copy article linkArticle link copied!
- Jason E. McDermott*Jason E. McDermott*E-mail: [email protected]. Tel: 509-372-4360.Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington 99352, United StatesDepartment of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon 97239, United StatesMore by Jason E. McDermott
- Jon M. JacobsJon M. JacobsEnvironmental and Molecular Sciences Division, Pacific Northwest National Laboratory, Richland, Washington 99352, United StatesMore by Jon M. Jacobs
- Nathaniel J. MerrillNathaniel J. MerrillBiological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington 99352, United StatesMore by Nathaniel J. Merrill
- Hugh D. MitchellHugh D. MitchellBiological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington 99352, United StatesMore by Hugh D. Mitchell
- Osama A. ArshadOsama A. ArshadBiological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington 99352, United StatesMore by Osama A. Arshad
- Ryan McClureRyan McClureBiological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington 99352, United StatesMore by Ryan McClure
- Justin TeeguardenJustin TeeguardenEnvironmental and Molecular Sciences Division, Pacific Northwest National Laboratory, Richland, Washington 99352, United StatesMore by Justin Teeguarden
- Rajendra P. GajulaRajendra P. GajulaDepartment of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, Washington 99202, United StatesMore by Rajendra P. Gajula
- Kenneth I. PorterKenneth I. PorterDepartment of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, Washington 99202, United StatesMore by Kenneth I. Porter
- Brieann C. SatterfieldBrieann C. SatterfieldSleep and Performance Research Center, Washington State University, Spokane, Washington 99202, United StatesDepartment of Translational Medicine and Physiology, Washington State University, Spokane, Washington 99202, United StatesMore by Brieann C. Satterfield
- Kirsie R. LundholmKirsie R. LundholmSleep and Performance Research Center, Washington State University, Spokane, Washington 99202, United StatesDepartment of Translational Medicine and Physiology, Washington State University, Spokane, Washington 99202, United StatesMore by Kirsie R. Lundholm
- Debra J. SkeneDebra J. SkeneFaculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH, United KingdomMore by Debra J. Skene
- Shobhan GaddameedhiShobhan GaddameedhiDepartment of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27695, United StatesCenter for Human Health and the Environment, North Carolina State University, Raleigh, North Carolina 27695, United StatesMore by Shobhan Gaddameedhi
- H. P. A. Van DongenH. P. A. Van DongenSleep and Performance Research Center, Washington State University, Spokane, Washington 99202, United StatesDepartment of Translational Medicine and Physiology, Washington State University, Spokane, Washington 99202, United StatesMore by H. P. A. Van Dongen
Abstract

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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This article is cited by 2 publications.
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- Matt Spick, Cheryl M Isherwood, Lee Gethings, Hana Hassanin, Daan R van der Veen, Debra J. Skene, Jonathan D Johnston. Rhythmic variation in proteomics: challenges and opportunities for statistical power and biomarker identification. 2024https://doi.org/10.1101/2024.06.28.601121
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