释放的Lipokine 12,13-diHOME在心脏功能中的新型内分泌作用
Kelsey M Pinckard1,2, Vikram K Shettigar1,2, Katherine R Wright1,2
1Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus (K.M.P., V.K.S., K.R.W., E.A., L.A.B., P.V., R.S.D., D.H.-S., P.J.A., A.C.L., E.D.L., S.V.R., L.E.W., D.G.P., M.T.Z., K.I.S.).
棕色脂肪组织 (BAT) 移植通过释放脂素12,13-diHOME来改善心脏功能. 这种分子增强了心肌细胞的呼吸和心脏血动力学, 为心脏病提供了新的治疗点.
科学领域:
- 心血管生物学
- 代谢疾病研究
- 内分泌学
背景情况:
- 棕色脂肪组织 (BAT) 在热生成中起作用,与新陈代谢健康有关.
- 虽然BAT可以预防心血管疾病,但其对心脏功能的直接影响尚不清楚.
- 最近的发现表明BAT作为内分泌器官,促使研究其信号通路.
研究的目的:
- 研究棕色脂肪组织 (BAT) 在心脏功能中介的直接作用.
- 确定BAT影响心脏的特定分子机制.
主要方法:
- 使用棕色脂肪组织 (BAT) 移植小鼠模型.
- 进行脂管学以确定关键信号分子,特别是12,13-二-9Z-八酸 (12,13-diHOME).
- 在NOS1缺乏的小鼠模型和隔离心肌细胞中研究了12,13- diHOME的作用,并分析了人类患者的数据.
主要成果:
- 通过释放12,13-diHOME改善了心脏功能.
- 12,13-diHOME的过度表达抵消了高脂肪饮食引起的心脏功能障碍和重塑.
- 12,13-diHOME增强了心肌细胞线粒体呼吸和心脏血液动力学,依赖于NOS1.
- 在人类心脏病患者中观察到12,13- diHOME的水平下降.
结论:
- 棕色脂肪组织 (BAT) 作为内分泌器官,增强心脏功能.
- 利波金12,13-diHOME通过NOS1和循环调解了BAT对心脏的益处.
- 这一发现将12,13-diHOME作为心血管疾病的潜在治疗点.
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