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Role of Proinflammatory Cytokines in Feedback Modulation of Circadian Clock Gene Rhythms by Saturated Fatty Acids

Proinflammatory signaling cascades have been implicated in the mechanism by which high fat diet (HFD) and saturated fatty acids (SFA) modulate fundamental circadian properties of peripheral clocks. Because the cytokines TNFα and IL-6 are key signals in HFD- and SFA-induced proinflammatory responses...

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Autores principales: Kim, Sam-Moon, Neuendorff, Nichole, Earnest, David J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586641/
https://www.ncbi.nlm.nih.gov/pubmed/31222133
http://dx.doi.org/10.1038/s41598-019-45322-9
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author Kim, Sam-Moon
Neuendorff, Nichole
Earnest, David J.
author_facet Kim, Sam-Moon
Neuendorff, Nichole
Earnest, David J.
author_sort Kim, Sam-Moon
collection PubMed
description Proinflammatory signaling cascades have been implicated in the mechanism by which high fat diet (HFD) and saturated fatty acids (SFA) modulate fundamental circadian properties of peripheral clocks. Because the cytokines TNFα and IL-6 are key signals in HFD- and SFA-induced proinflammatory responses that ultimately lead to systemic insulin resistance, the present study examined the roles of these cytokines in the feedback modulation of peripheral circadian clocks by the proinflammatory SFA, palmitate. IL-6 and TNFα secretion in Bmal1-dLuc fibroblast cultures was increased during palmitate treatment although the time course and amplitude of the inductive response differed between these cytokines. Similar to the time-dependent phase shifts observed in response to palmitate, treatment with IL-6 or with the low dose (0.1 ng/ml) of TNFα at hour 12 (i.e., after forskolin synchronization) induced phase advances of fibroblast Bmal1-dLuc rhythms. In complementary experiments, treatment with neutralizing antibodies against these proinflammatory cytokines or their receptors to inhibit of IL-6- or TNFα-mediated signaling repressed palmitate-induced phase shifts of the fibroblast clock. These studies suggest that TNFα, IL-6 and other proinflammatory cytokines may mediate the feedback modulation of peripheral circadian clocks by SFA-induced inflammatory signaling.
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spelling pubmed-65866412019-06-26 Role of Proinflammatory Cytokines in Feedback Modulation of Circadian Clock Gene Rhythms by Saturated Fatty Acids Kim, Sam-Moon Neuendorff, Nichole Earnest, David J. Sci Rep Article Proinflammatory signaling cascades have been implicated in the mechanism by which high fat diet (HFD) and saturated fatty acids (SFA) modulate fundamental circadian properties of peripheral clocks. Because the cytokines TNFα and IL-6 are key signals in HFD- and SFA-induced proinflammatory responses that ultimately lead to systemic insulin resistance, the present study examined the roles of these cytokines in the feedback modulation of peripheral circadian clocks by the proinflammatory SFA, palmitate. IL-6 and TNFα secretion in Bmal1-dLuc fibroblast cultures was increased during palmitate treatment although the time course and amplitude of the inductive response differed between these cytokines. Similar to the time-dependent phase shifts observed in response to palmitate, treatment with IL-6 or with the low dose (0.1 ng/ml) of TNFα at hour 12 (i.e., after forskolin synchronization) induced phase advances of fibroblast Bmal1-dLuc rhythms. In complementary experiments, treatment with neutralizing antibodies against these proinflammatory cytokines or their receptors to inhibit of IL-6- or TNFα-mediated signaling repressed palmitate-induced phase shifts of the fibroblast clock. These studies suggest that TNFα, IL-6 and other proinflammatory cytokines may mediate the feedback modulation of peripheral circadian clocks by SFA-induced inflammatory signaling. Nature Publishing Group UK 2019-06-20 /pmc/articles/PMC6586641/ /pubmed/31222133 http://dx.doi.org/10.1038/s41598-019-45322-9 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Kim, Sam-Moon
Neuendorff, Nichole
Earnest, David J.
Role of Proinflammatory Cytokines in Feedback Modulation of Circadian Clock Gene Rhythms by Saturated Fatty Acids
title Role of Proinflammatory Cytokines in Feedback Modulation of Circadian Clock Gene Rhythms by Saturated Fatty Acids
title_full Role of Proinflammatory Cytokines in Feedback Modulation of Circadian Clock Gene Rhythms by Saturated Fatty Acids
title_fullStr Role of Proinflammatory Cytokines in Feedback Modulation of Circadian Clock Gene Rhythms by Saturated Fatty Acids
title_full_unstemmed Role of Proinflammatory Cytokines in Feedback Modulation of Circadian Clock Gene Rhythms by Saturated Fatty Acids
title_short Role of Proinflammatory Cytokines in Feedback Modulation of Circadian Clock Gene Rhythms by Saturated Fatty Acids
title_sort role of proinflammatory cytokines in feedback modulation of circadian clock gene rhythms by saturated fatty acids
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586641/
https://www.ncbi.nlm.nih.gov/pubmed/31222133
http://dx.doi.org/10.1038/s41598-019-45322-9
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