Visfatin Modulates Angiogenesis and Apoptosis in Porcine Luteal Cells via INSR, MAPK, and AKT Pathways

Abstract

Visfatin, a multifunctional adipokine, plays a crucial role in ovarian physiology. This study examines its effects on the level of selected angiogenesis and apoptosis factors in the porcine corpus luteum (CL). Using in vitro cultures of luteal cells, we analyzed the effects of visfatin on key angiogenic factors (VEGF family, PDGF, bFGF2, ANG, and iNOS) and their receptors. Additionally, we assessed luteal cell viability and apoptosis by measuring caspase activity, DNA fragmentation, and transcript levels of apoptotic factors. We noted that visfatin mostly decreases the expression of angiogenic factors and their receptors during the luteal phase except for VEGFC, VEGFR3 on Days 2–3 of the estrous cycle, and VEGFB, VEGFD, VEGFR1, VEGFR2, FGFR2 on Days 14–16 of the estrous cycle, which were upregulated. Moreover, visfatin inhibits apoptosis by downregulating caspase-3, -8, -9, BAX, and caspase 3/7 activity while increasing BCL-2 and luteal cells viability. Treatment with FK866, nicotinamide phosphoribosyltransferase (NAMPT) inhibitor, largely disrupted observed effects, highlighting the NAMPT-dependent function of visfatin. Moreover, visfatin suppressed VEGF-A levels via insulin receptor and MAPK, while insulin receptor, MAPK, and AKT pathways mediated the inhibition of caspase 3/7 activity. These findings suggest that visfatin regulates apoptosis and angiogenesis in the porcine CL.