Department of Molecular Physiology and Biophysics, School of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
VA Tennessee Valley Healthcare System, Nashville, Tennessee, USA.
Compr Physiol. 2022 Jun 29;12(3):3641-3663. doi: 10.1002/cphy.c210039.
Iron is an essential metal element whose bioavailability is tightly regulated. Under normal conditions, systemic and cellular iron homeostases are synchronized for optimal function, based on the needs of each system. During metabolic dysfunction, this synchrony is lost, and markers of systemic iron homeostasis are no longer coupled to the iron status of key metabolic organs such as the liver and adipose tissue. The effects of dysmetabolic iron overload syndrome in the liver have been tied to hepatic insulin resistance, nonalcoholic fatty liver disease, and nonalcoholic steatohepatitis. While the existence of a relationship between iron dysregulation and metabolic dysfunction has long been acknowledged, identifying correlative relationships is complicated by the prognostic reliance on systemic measures of iron homeostasis. What is lacking and perhaps more informative is an understanding of how cellular iron homeostasis changes with metabolic dysfunction. This article explores bidirectional relationships between different proteins involved in iron homeostasis and metabolic dysfunction in the liver. © 2022 American Physiological Society. Compr Physiol 12:3641-3663, 2022.
铁是一种必需的金属元素，其生物利用度受到严格调节。在正常情况下，基于每个系统的需求，全身和细胞内的铁动态平衡是同步的，以实现最佳功能。在代谢功能障碍期间，这种同步性丧失，并且全身铁动态平衡的标志物不再与肝脏和脂肪组织等关键代谢器官的铁状态相关联。肝内代谢性铁过载综合征的影响与肝胰岛素抵抗、非酒精性脂肪肝和非酒精性脂肪性肝炎有关。虽然铁失调与代谢功能障碍之间的关系早已得到承认，但由于对全身铁动态平衡的系统测量的预后依赖性，确定相关关系变得复杂。缺乏的可能是更具信息量的理解，即细胞内铁动态平衡如何随代谢功能障碍而变化。本文探讨了肝脏中铁动态平衡和代谢功能障碍相关不同蛋白质之间的双向关系。© 2022 美国生理学会。综合生理学 12:3641-3663,2022。
