Lipocalin 2 is expressed in MLO-Y4 osteocytes and regulated by the peroxisome proliferator activated receptor α agonist fenofibrate.
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Background: Lipocalin 2 is highly expressed and secreted from osteoblasts in mice. Lately, bone-derived lipocalin 2 has been shown to suppress appetite by binding to the MC4R in hypothalamus. In the present study we wanted to examine whether the PPARα agonist fenofibrate exerts its weight-reducing effect through stimulation of lipocalin 2 secretion.Methods: The murine pre-osteoblast and osteocyte cell lines (MC3T3-E1 and MLO-Y4) were incubated with DMSO (control) and fenofibrate dissolved in DMSO for 24 and 72 hours. MC3T3-E1 cells were exposed to fenofibrate 10 µM, and MLO-Y4 cells to 1 and 10 µM. Lipocalin 2 in cell medium and lysate was measured by ELISA, and lipocalin 2 mRNA in MLO-Y4 cells by RTPCR. Lipocalin 2 was also analyzed in plasma from ovariectomized (OVX) rats exposed to fenofibrate (90 mg/kg/d) for eight weeks and in OVX controls. Results: Lipocalin 2 mRNA was significantly and highly expressed in MLO-Y4 cells after exposure to fenofibrate 1 and 10 µM for 24 hours. No significant differences in lipocalin levels were observed in cell medium or lysate from MC3T3-E1 and MLO-Y4 cells after incubation with fenofibrate. The highest levels of lipocalin 2 were seen after exposure of MLO-Y4 cells to fenofibrate 1 µM for 72 hours. The amount of lipocalin 2 appeared to be modest in MC3T3-E1 cells. Plasma levels of lipocalin 2 were higher in OVX rats exposed to fenofibrate than in controls, however, not significantly.Conclusion: We show for the first time that lipocalin 2 is expressed, translated and secreted from the osteocyte cell line MLO-Y4, and that lipocalin 2 mRNA expression is upregulated by fenofibrate.