Physiological Roles of Group X-secreted Phospholipase A2 in Reproduction, Gastrointestinal Phospholipid Digestion, and Neuronal Function*
Physiological Roles of Group X-secreted Phospholipase A2 in Reproduction, Gastrointestinal Phospholipid Digestion, and Neuronal Function*
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DOI：
10.1074/jbc.m110.206755
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发表时间：
2011-01
期刊：
影响因子：
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通讯作者：
Hiroyasu Sato;Y. Isogai;Seiko Masuda;Y. Taketomi;Y. Miki;D. Kamei;S. Hara;Tetsuyuki Kobayashi;Y. Ishikawa;T. Ishii;K. Ikeda;R. Taguchi;Y. Ishimoto;N. Suzuki;Y. Yokota;K. Hanasaki;Toshiko Suzuki-Yamamoto;Kei Yamamoto;M. Murakami
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文献类型：
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作者：
Hiroyasu Sato;Y. Isogai;Seiko Masuda;Y. Taketomi;Y. Miki;D. Kamei;S. Hara;Tetsuyuki Kobayashi;Y. Ishikawa;T. Ishii;K. Ikeda;R. Taguchi;Y. Ishimoto;N. Suzuki;Y. Yokota;K. Hanasaki;Toshiko Suzuki-Yamamoto;Kei Yamamoto;M. Murakami
虽然分泌型磷脂酶A2(SPLA2)家族被普遍认为参与炎症和动脉粥样硬化等病理事件，但X组sPLA2(sPLA2-X)在生殖器官、胃肠道和周围神经元等限制性部位的相对高表达和结构性表达提出了一个问题，即该酶在生殖、消化和神经系统的生理中所起的作用。在这里，我们使用基因中断或转基因过表达sPLA2-X的小鼠来阐明该酶在这些位置的动态平衡功能。我们的结果表明，sPLA2-X调节1)精子而不是卵母细胞的生育能力，超出鞭毛运动的阶段，2)胃肠道磷脂消化，其扰动最终与肥胖减少的瘦肉型延迟开始有关，降低血浆瘦素，并改善肌肉对胰岛素的耐受性，3)背根神经节的神经发生和外周痛觉持续时间。因此，除了先前提出的炎症作用外，sPLA2-X还参与了男性生育、与肥胖有关的胃肠道磷脂消化以及神经元生长和感觉等生理过程。
Although the secreted phospholipase A2 (sPLA2) family has been generally thought to participate in pathologic events such as inflammation and atherosclerosis, relatively high and constitutive expression of group X sPLA2 (sPLA2-X) in restricted sites such as reproductive organs, the gastrointestinal tract, and peripheral neurons raises a question as to the roles played by this enzyme in the physiology of reproduction, digestion, and the nervous system. Herein we used mice with gene disruption or transgenic overexpression of sPLA2-X to clarify the homeostatic functions of this enzyme at these locations. Our results suggest that sPLA2-X regulates 1) the fertility of spermatozoa, not oocytes, beyond the step of flagellar motility, 2) gastrointestinal phospholipid digestion, perturbation of which is eventually linked to delayed onset of a lean phenotype with reduced adiposity, decreased plasma leptin, and improved muscle insulin tolerance, and 3) neuritogenesis of dorsal root ganglia and the duration of peripheral pain nociception. Thus, besides its inflammatory action proposed previously, sPLA2-X participates in physiologic processes including male fertility, gastrointestinal phospholipid digestion linked to adiposity, and neuronal outgrowth and sensing.