Chlamydia pneumoniae exploits adipocyte lipid chaperone FABP4 to facilitate fat mobilization and intracellular growth in murine adipocytes
Chlamydia pneumoniae exploits adipocyte lipid chaperone FABP4 to facilitate fat mobilization and intracellular growth in murine adipocytes
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肺炎衣原体利用脂肪细胞脂质伴侣 FABP4 促进小鼠脂肪细胞的脂肪动员和细胞内生长
DOI：
10.1016/j.bbrc.2017.11.005
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Hiromatsu Kenji
中科院分区：
文献类型：
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作者：
Walenna Nirwana Fitriani;Kurihara Yusuke;Chou Bin;Ishii Kazunari;Soejima Toshinori;Itoh Ryota;Shimizu Akinori;Ichinohe Takeshi;Hiromatsu Kenji
脂肪酸结合蛋白4（FABP 4）是一种主要在脂肪细胞和巨噬细胞中表达的胞质脂质伴侣，调节脂质通量、运输、信号传导和代谢。最近的研究表明，FABP 4调节代谢和炎症途径，在小鼠模型中，其抑制可以改善2型糖尿病和动脉粥样硬化。然而，FABP 4在细菌感染、宿主和病原体之间的代谢串扰以及细菌致病中的作用尚未研究。作为一种专性胞内病原体，肺炎衣原体需要从宿主细胞中获取ATP和脂质等营养物质。在这里，我们表明，C。肺炎克雷伯氏菌通过诱导激素敏感脂肪酶（HSL）介导的脂解作用成功地感染鼠脂肪细胞并在鼠脂肪细胞中增殖。化学抑制或遗传操作HSL可显著抑制C.脂肪细胞中的肺炎。利用游离脂肪酸通过β-氧化产生ATP，C。pneumoniae肺炎successfully篡夺for its replication复制.引人注目的是，FABP 4的化学抑制或遗传沉默显着消除了C。肺炎杆菌感染诱导的脂解和释放的FFA的动员，导致脂肪细胞中细菌生长减少。这些结果表明，C.肺炎链球菌利用宿主FABP 4促进脂肪细胞中的脂肪动员和细胞内复制。这项工作揭示了细胞内病原体通过劫持宿主脂质代谢途径获得能量的新策略。
Fatty acid-binding protein 4 (FABP4), a cytosolic lipid chaperone predominantly expressed in adipocytes and macrophages, modulates lipid fluxes, trafficking, signaling, and metabolism. Recent studies have demonstrated that FABP4 regulates metabolic and inflammatory pathways, and in mouse models its inhibition can improve type 2 diabetes mellitus and atherosclerosis. However, the role of FABP4 in bacterial infection, metabolic crosstalk between host and pathogen, and bacterial pathogenesis have not been studied. As an obligate intracellular pathogen, Chlamydia pneumoniae needs to obtain nutrients such as ATP and lipids from host cells. Here, we show that C. pneumoniae successfully infects and proliferates in murine adipocytes by inducing hormone sensitive lipase (HSL)-mediated lipolysis. Chemical inhibition or genetic manipulation of HSL significantly abrogated the intracellular growth of C. pneumoniae in adipocytes. Liberated free fatty acids were utilized to generate ATP via b-oxidation, which C. pneumoniae usurped for its replication. Strikingly, chemical inhibition or genetic silencing of FABP4 significantly abrogated C. pneumoniae infection-induced lipolysis and mobilization of liberated FFAs, resulting in reduced bacterial growth in adipocytes. Collectively, these results demonstrate that C. pneumoniae exploits host FABP4 to facilitate fat mobilization and intracellular replication in adipocytes. This work uncovers a novel strategy used by intracellular pathogens for acquiring energy via hijacking of the host lipid metabolism pathway.