Role of Proinflammatory Cytokines in Feedback Modulation of Circadian Clock Gene Rhythms by Saturated Fatty Acids. Academic Article uri icon


  • 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 TNF 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 TNF 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 (0.1ng/ml) of TNF 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 TNF-mediated signaling repressed palmitate-induced phase shifts of the fibroblast clock. These studies suggest that TNF, IL-6 and other proinflammatory cytokines may mediate the feedback modulation of peripheral circadian clocks by SFA-induced inflammatory signaling.

published proceedings

  • Sci Rep

altmetric score

  • 9.95

author list (cited authors)

  • Kim, S., Neuendorff, N., & Earnest, D. J.

citation count

  • 8

complete list of authors

  • Kim, Sam-Moon||Neuendorff, Nichole||Earnest, David J

publication date

  • January 2019