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Hypothesis and Theory ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurol. | doi: 10.3389/fneur.2018.00818

Blind spot for sedentarism: redefining the diseasome of physical inactivity in view of circadian system and the irisin/BDNF axis

 Judit Zsuga1, 2*, Csaba E. More2, 3, Tamas Erdei2, Csaba Papp1, 2,  Szilvia Harsanyi1, 2 and  Rudolf Gesztelyi2
  • 1Department of Health System Management and Quality Management in Health Care, University of Debrecen, Hungary
  • 2Department of Pharmacology and Pharmacotherapy, University of Debrecen, Hungary
  • 3Department of Psychiatry, University of Debrecen, Hungary

The term “diseasome of physical inactivity” was coined by Pedersen to explain clustering of chronic diseases linked to physical inactivity. Accordingly, physical inactivity per se contributes to the accumulation of visceral fat, which, generates chronic low-grade systemic inflammation, contributes to emergence of chronic, non-communicable diseases (type 2 diabetes, cardiovascular diseases, colon cancer, postmenopausal breast cancer, dementia, depression). Diversity of these disorders posits the possible involvement of a supraphysiological system.
The circadian system is omnipresent in virtually every cell, it enables adaptation to the diurnal environment, by regulating diverse, fundamental processes (metabolism, locomotor activity, sleep-wake cycles etc.). It is hierarchically organized, with the suprachiasmatic nucleus (SCN) being the master clock that entrains to the dark/light cycle and synchronizes subsidiary molecular clocks in the periphery. Insufficient photic entrainment also causes chronic disease evolution.
Recent identification of myokines opened new avenues regarding muscle-brain crosstalk. For example, irisin, may enter the central nervous system and induce brain-derived neurotrophic factor (BDNF) production in several brain areas. BDNF assumes significant role in gating light’s influence in the retinohypothalamic synapse, by having a permissive effect on glutamate signal transduction underlying photic entrainment.
Here we provide evidence to support the hypothesis that irisin may facilitate photic entrainment of the SCN, via BDNF. By this irisin opens up possible pathways for peripheral non-photic entrainment signals to exert influence on the master clock that is otherwise resistant to these. Furthermore, we suggest that intertwining processes of circadian, redox, inflammatory and myokine systems lay underneath the diseasome of physical inactivity.

Keywords: Circadian Rhythm, irisin, BDNF, Suprachiasmatic Nucleus, physical inactivity, entrainment

Received: 06 Apr 2018; Accepted: 10 Sep 2018.

Edited by:

Aurel Popa-Wagner, Department of Neurology, University Hospital Essen, Germany

Reviewed by:

Domenico De Berardis, Azienda Usl Teramo, Italy
Nadia Canu, Università degli Studi di Roma Tor Vergata, Italy  

Copyright: © 2018 Zsuga, More, Erdei, Papp, Harsanyi and Gesztelyi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Judit Zsuga, University of Debrecen, Department of Health System Management and Quality Management in Health Care, Debrecen, Hungary,