Fibronectin type III domain-containing 5 (FNDC5) is a transmembrane protein discovered in 2012 that is cleaved to release the adipokine-myokine, irisin. Originally described as an exercise hormone that browns white adipose tissue and increases glucose metabolism, irisin secretion also increases during periods of rapid adipose mobilization, such as the post-partum period in dairy cattle when ovarian activity is suppressed. The effect of irisin on follicle function is unclear, and may be species dependent. In this study we hypothesized that irisin may compromise granulosa cell function in cattle using a well-established in vitro cell culture model. We detected FNDC5 mRNA and both FNDC5 and cleaved irisin proteins in follicle tissue and in follicular fluid. Abundance of FNDC5 mRNA was increased by treatment of cells with the adipokine visfatin but not by other adipokines tested. Addition of recombinant irisin to granulosa cells decreased basal and IGF-1- and FSH-dependent estradiol and progesterone secretion, and increased cell proliferation but had no effect on viability. Irisin decreased GLUT1, GLUT3 and GLUT4 mRNA levels in granulosa cells and increased lactate release in culture medium. The mechanism of action is in part through MAPK3/1 but not Akt, MAPK14 or PRKAA. We conclude that irisin may regulate bovine folliculogenesis by modulating granulosa cell steroidogenesis and glucose metabolism.
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