# Irisin Modulates IFNT Signaling in Bovine Luteal Cells

## TL;DR

The study shows that irisin, a protein from fat tissue, boosts interferon signaling in cow luteal cells, possibly helping embryo development during energy stress.

## Contribution

This study is the first to show that irisin enhances IFNT signaling in bovine luteal cells without affecting steroid production or cell survival.

## Key findings

- FNDC4 and FNDC5 mRNA levels in bovine CL are higher in later developmental stages than in Early I.
- Irisin treatment increases interferon-stimulated genes MX1 and MX2 in luteal cells.
- Irisin does not affect steroidogenic enzymes, cell viability, or apoptosis markers in luteal cells.

## Abstract

Adipokines, bioactive proteins derived from adipose tissue, serve as intermediaries between energy status and reproduction, playing pivotal roles in ovarian physiology. Among them, members of the Fibronectin Type III domain‐containing the (FNDC) family, including FNDC4 and FNDC5 (the precursor of irisin), have emerged as key modulators of fertility. This study investigated the expression of FNDC4, FNDC5, and their receptors (ITGB1, ITGAV, ADGRF5) across different stages of bovine CL lifespan and evaluated irisin's effects on interferon tau (IFNT)‐mediated signaling in bovine luteal cells. The relative abundance of FNDC4 and FNDC5 mRNA was significantly greater in Early II, Middle, and Late phases when compared to the Early I. The expression of ITGB1 and ADGRF5 in bovine CL was significantly greater in the Early II, Middle, and Late phases than in the Early I phase, and the abundance of ITGAV mRNA did not differ between the evaluated phases. Also, it was observed that mRNA expression of all evaluated receptors was greater in CL of nonpregnant cows on Day 18 compared to pregnant cows. In vitro experiments demonstrated that irisin treatment enhanced interferon‐stimulated genes (ISGs) such as MX1 and MX2 in luteal cells, suggesting irisin potentiates IFNT signaling. Notably, irisin did not alter steroidogenic enzyme expression or affect cell viability, proliferation, or apoptosis markers, indicating its effects are specific to IFNT signaling pathways. The present study shows that the genes FNDC5 and FNDC4 are expressed in the bovine corpus luteum at different stages of development and that irisin increased ISGs expression in bovine luteal cells in vitro. The effects of irisin on CL function may be indirect, as plasma irisin increases during the postpartum negative energy balance in dairy cows. We propose that this is part of a compensatory mechanism to modulate IFNT signaling in CL cells and indirectly improve embryonic signaling mechanisms.