Spexin Acts as Novel Regulator for Bile Acid Synthesis.
Spexin Acts as Novel Regulator for Bile Acid Synthesis.
复制标题
Spexin 作为胆汁酸合成的新型调节剂
DOI：
10.3389/fphys.2018.00378
复制
发表时间：
2018
影响因子：
4
通讯作者：
Bian ZX
中科院分区：
文献类型：
--
作者：
Lin CY;Zhao L;Huang T;Lu L;Khan M;Liu J;Zhong LLD;Cai ZW;Fan BM;Wong AOL;Bian ZX
Spexin是一种新的激素，与肥胖和糖尿病有关，但其在脂质代谢中的生物功能意义尚不清楚。本研究的全球代谢组学分析揭示了Spexin(Ip)改变的多条代谢途径。在大鼠血清中注射，突出表现为几种胆汁酸代谢物的变化。Spexin(30 0μg/kg)可显著降低大鼠肝脏和循环总胆汁酸水平。相应地，Spexin经腹腔注射治疗。给药28天后，C57BL/6J小鼠血清总胆汁酸和胆囊重均显著下降。在肝-肠循环系统中，Spexin有效地降低了小鼠肝脏和胆汁中的TBA水平，但不能降低肠道中的TBA水平。不出所料，肝胆固醇7α羟基酶1(CYP7A1)的表达被Spexin抑制。GALR2和GALR3拮抗剂均能逆转Spexin对血清总胆红素和7-羟基-4-胆固酮-3-酮(7-α-hyxy-4-cholesten-3-one，C4)浓度及肝脏细胞色素P7A1表达的抑制作用。91例健康志愿者血清Spexin与总胆固醇(TC)、总胆汁酸(TBA)、鹅去氧胆酸(TCDCA)、甘鹅脱氧胆酸(GCDCA)呈负相关。这些发现阐明了spexin在胆汁酸合成和代谢调节中的内在重要性。
Spexin is a novel hormone involved in obesity and diabetes while its biofunctional significance in lipid metabolism is still to be comprehended. Global metabolomic analysis in the present study revealed multiple metabolic pathways altered by spexin intraperitoneal (i.p.) injection in rat serum, which are highlighted by the changes in several bile acid metabolites. In rats, spexin (300 μg/kg) could dramatically reduce hepatic and circulating total bile acids (TBA) level compared with the controls. Correspondingly, treatment with spexin by i.p. injection for 28 days led to significant decrease in serum TBA and gallbladder weight in C57BL/6J mice. In enterohepatic circulation system, spexin effectively reduced TBA levels in mouse liver and gallbladder but not the intestine. Hepatic cholesterol 7α-hydroxylase 1 (CYP7A1) expression, unsurprisingly, was suppressed by spexin injection. Both GALR2 and GALR3 antagonists reversed the inhibitory effects of spexin on concentrations of serum TBA and 7 α-hydroxy-4-cholesten-3-one (C4), and hepatic CYP7A1 expression. Finally, negative correlations were observed between serum spexin and total cholesterol (TC), total bile acid (TBA), tauro-chenodeoxycholate (TCDCA), as well as glycochenodeoxycholate (GCDCA) in 91 healthy volunteers. These findings illuminate the intrinsic importance of spexin in the regulation of bile acid synthesis and metabolism.
登录
查看更多内容
影响因子：
5.8
作者：
Kumar, Seema;Hossain, Jobayer;Balagopal, P. Babu
通讯作者：
Balagopal, P. Babu
DOI：
10.1073/pnas.1318066111
发表时间：
2014-05-13
影响因子：
11.1
作者：
Brunner, Susanne M.;Farzi, Aitak;Kofler, Barbara
通讯作者：
Kofler, Barbara
影响因子：
3.5
作者：
AXELSON, M;ALY, A;SJOVALL, J
通讯作者：
SJOVALL, J
肝脏中胆固醇7alpha-羟化酶在肝脏中的转基因表达可防止小脂饮食诱导的肥胖和胰岛素抵抗。
影响因子：
13.5
作者：
Li, Tiangang;Owsley, Erika;Matozel, Michelle;Hsu, Peter;Novak, Colleen M.;Chiang, John Y. L.
通讯作者：
Chiang, John Y. L.
影响因子：
3.8
作者：
Kumar S;Hossain MJ;Javed A;Kullo IJ;Balagopal PB
通讯作者：
Balagopal PB