BMAL1/PGC1α4-FNDC5/irisin axis impacts distinct outcomes of time-of-day resistance exercise.

Abstract in brief

• The study shows that resistance exercises performed at different times of day lead to varying training results and metabolic benefits in humans, linked to the rhythmic levels of the myokine irisin, which is regulated by circadian factors like BMAL1 and PGC-1α.
• Mice trained during their active phase, when FNDC5/irisin levels are higher, experience greater muscle growth and better metabolic health compared to those trained during rest phases; these effects depend on the presence of FNDC5, as knockout mice do not show these benefits.
• Mechanistically, the circadian regulator BMAL1 and PGC-1α promote the transcription of FNDC5/irisin, which signals through V integrin in muscle, linking circadian rhythms to exercise outcomes and metabolic regulation.