小柯机器人

乳酸（LA）通过结合可溶性腺苷酸环化酶（sAC）调节铁代谢，山东第一医科大学山东省医学科学院Sijin Liu研究组报道了这一发现。2023年7月21日出版的《细胞-代谢》杂志发表了这项成果。

研究人员发现LA与正常肝细胞中的可溶性腺苷酸环化酶结合，并通过增加铁调素的表达来影响小鼠全身性铁稳态。体外、体内和计算机实验表明，LA-sAC相互作用提高了环磷酸腺苷（cAMP）的水平，从而激活了PKA-Smad1/5/8信号通路，进而增强了铁调素的转录。

研究人员在野生型小鼠和铁稳态紊乱的小鼠中验证了该调节轴。LA还调节人类在休息和大量运动时产生高LA时铁调素的转录。该研究将高乳酸血症与缺铁联系起来，为运动员和乳酸酸中毒患者贫血的原因提供了解释。

据悉，在运动和许多疾病（如癌症）中可能会产生过量的乳酸。高乳酸血症患者通常具有贫血、血清铁降低和铁调素升高的症状，铁调素是铁代谢的关键调节因子。然而，尚不清楚LA是否以及如何调节铁调素的表达。

附：英文原文

Title: Lactate modulates iron metabolism by binding soluble adenylyl cyclase

Author: Wei Liu, Shuping Zhang, Quanjin Li, Yue Wu, Xuan Jia, Wenya Feng, Zhaolong Li, Yali Shi, Qingzhi Hou, Juan Ma, Yajun Liu, Pu Gao, Tomas Ganz, Sijin Liu

Issue&Volume: 2023-07-21

Abstract: Overproduction of lactate (LA) can occur during exercise and in many diseases suchas cancers. Individuals with hyperlactatemia often display anemia, decreased serumiron, and elevated hepcidin, a key regulator of iron metabolism. However, it is unknownwhether and how LA regulates hepcidin expression. Here, we show LA binds to solubleadenylyl cyclase (sAC) in normal hepatocytes and affects systemic iron homeostasisin mice by increasing hepcidin expression. Comprehensive in vitro, in vivo, and in silico experiments show that the LA-sAC interaction raises cyclic adenosine monophosphate(cAMP) levels, which activates the PKA-Smad1/5/8 signaling pathway to increase hepcidintranscription. We verified this regulatory axis in wild-type mice and in mice withdisordered iron homeostasis. LA also regulates hepcidin in humans at rest and subjectedto extensive exercise that produce elevated LA. Our study links hyperlactatemia toiron deficiency, offering a mechanistic explanation for anemias seen in athletes andpatients with lactic acidosis.

DOI: 10.1016/j.cmet.2023.06.017

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00227-9

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