Rudolph Emily L, Chin LiKang
Department of Biomedical Engineering, Widener University, Chester, PA 19013, USA.
Curr Issues Mol Biol. 2024 Jul 7;46(7):7134-7146. doi: 10.3390/cimb46070425.
With the ongoing obesity epidemic, the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is expected to rise and necessitates a greater understanding of how the disease proceeds from benign excess lipid in hepatocytes to liver fibrosis and eventually to liver cancer. MASLD is caused, at least in part, by hepatocytes' storage of free fatty acids (FAs) that dysfunctional adipocytes are no longer able to store, and therefore, MASLD is a disease that involves both the liver and adipose tissues. The disease progression is not only facilitated by biochemical signals, but also by mechanical cues such as the increase in stiffness often seen with fibrotic fatty livers. The change in stiffness and accumulation of excess lipid droplets impact the ability of a cell to mechanosense and mechanotranduce, which perpetuates the disease. A mechanosensitive protein that is largely unexplored and could serve as a potential therapeutic target is the intermediate filament vimentin. In this review, we briefly summarize the recent research on hepatocyte and adipocyte mechanobiology and provide a synopsis of studies on the varied, and sometimes contradictory, roles of vimentin. This review is intended to benefit and encourage future studies on hepatocyte and adipocyte mechanobiology in the context of MASLD and obesity.
随着肥胖症的不断流行，代谢功能障碍相关脂肪性肝病（MASLD）的患病率预计将会上升，这就需要我们更深入地了解该疾病是如何从肝细胞内良性的脂质过剩发展为肝纤维化并最终发展为肝癌的。MASLD至少部分是由肝细胞储存功能失调的脂肪细胞不再能够储存的游离脂肪酸（FAs）所引起的，因此，MASLD是一种涉及肝脏和脂肪组织的疾病。疾病的进展不仅受到生化信号的促进，还受到机械信号的影响，比如纤维化脂肪肝中常见的硬度增加。硬度的变化和过量脂滴的积累会影响细胞的机械感知和机械转导能力，从而使疾病持续发展。一种在很大程度上未被探索且可作为潜在治疗靶点的机械敏感蛋白是中间丝波形蛋白。在这篇综述中，我们简要总结了近期关于肝细胞和脂肪细胞力学生物学的研究，并概述了关于波形蛋白的多样且有时相互矛盾的作用的研究。这篇综述旨在为未来在MASLD和肥胖背景下对肝细胞和脂肪细胞力学生物学的研究提供帮助并起到鼓励作用。
