Effect of the Myokine Irisin on Circadian Rhythm of Voluntary Locomotor Activity in Rats

The endogenous circadian oscillator, located in the mammalian suprachiasmatic nucleus (SCN), generates its own rhythm, the period of which typically does not precisely match the 24-h duration of a day and hence requires entrainment with the geophysical circadian rhythm of the external world. One of the most important non-photic mechanisms of circadian clock entrainment is based on the information about the pattern and intensity of physical activity. Within this mechanism, the role of the key molecular entrainment factor is attributed to the myokine irisin. Meanwhile, irisin effects on behavioral circadian rhythms remain unexplored. In the present study, the effects of triple intranasal administration of irisin (0.5 µg) at various projected time points across three consecutive circadian cycles (ZT 2, ZT 6, ZT 10, ZT 14, ZT 18, and ZT 22) on the circadian rhythm of voluntary locomotor activity in a running wheel under conditions of constant darkness were investigated for the first time in experiments on male Wistar rats. Irisin administration at ZT 6 led to a statistically significant advanced phase shift of the rhythm’s acrophase median by 0.6 h (p < 0.05), accompanied by a decrease in total locomotor activity by 1666 wheel revolutions per day (p < 0.05). Intranasal irisin administration at any other time points of the projected circadian cycle did not induce statistically significant phase shifts or changes in total locomotor activity. Irisin did not alter the period of the circadian rhythm, regardless of the time of administration. The obtained results provide experimental evidence for the role of endogenous irisin as a non-photic entraining factor for the circadian system, manifesting itself in the absence of the primary physiological zeitgeber, cyclic afferentation from retinal photoreceptors, in accordance with the daily pattern and intensity of muscle activity within the muscle–brain functional axis.