Thon Mina, Hosoi Toru, Ozawa Koichiro
Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Sci Rep. 2016 Sep 28;6:34312. doi: 10.1038/srep34312.
Leptin, an adipocyte-derived hormone, centrally regulates energy homeostasis. Overlaps in the regulation of glucose and energy homeostasis have been reported between leptin and insulin. However, the effects of insulin on leptin's actions in the central nervous system (CNS) have not yet been elucidated in detail. In the present study, we found that insulin potentiated leptin's actions through GRP78 in the neuronal cell line, SH-SY5Y-ObRb. Since insulin induces GRP78, we speculated that it may also enhance leptin's actions through this induction. We found that insulin enhanced leptin-induced STAT3 phosphorylation and this effect was ameliorated by the knockdown of GRP78. The role of GRP78 in leptin's actions was also confirmed by impairments in leptin-induced STAT3 phosphorylation in HEK293-ObRb cells in which GRP78 was knocked down. Furthermore, we found that the overexpression of GRP78 enhanced leptin-induced STAT3 phosphorylation. These results suggest that GRP78 plays an important role in leptin's actions. Furthermore, insulin may enhance the leptin-induced activation of STAT3 by inducing GRP78, which may provide an important connection between insulin and leptin in the CNS.
瘦素是一种由脂肪细胞分泌的激素，可在中枢调节能量平衡。据报道，瘦素与胰岛素在调节葡萄糖和能量平衡方面存在重叠。然而，胰岛素对瘦素在中枢神经系统（CNS）中作用的影响尚未得到详细阐明。在本研究中，我们发现胰岛素通过神经元细胞系SH-SY5Y-ObRb中的GRP78增强了瘦素的作用。由于胰岛素可诱导GRP78，我们推测它也可能通过这种诱导作用增强瘦素的作用。我们发现胰岛素增强了瘦素诱导的STAT3磷酸化，而GRP78的敲低可改善这种作用。在GRP78被敲低的HEK293-ObRb细胞中，瘦素诱导的STAT3磷酸化受损也证实了GRP78在瘦素作用中的作用。此外，我们发现GRP78的过表达增强了瘦素诱导的STAT3磷酸化。这些结果表明GRP78在瘦素的作用中起重要作用。此外，胰岛素可能通过诱导GRP78增强瘦素诱导的STAT3激活，这可能在中枢神经系统中提供胰岛素和瘦素之间的重要联系。
