Metabolic zonation refers to the spatial separation of metabolic functions along the sinusoidal axes of the liver. This phenomenon forms the foundation for adjusting hepatic metabolism to physiological requirements in health and disease (e.g., metabolic dysfunction-associated steatotic liver disease/MASLD). Zonated metabolic functions are influenced by zonal morphological abnormalities in the liver, such as periportal fibrosis and pericentral steatosis. We aim to analyze the interplay between microperfusion, oxygen gradient, fat metabolism and resulting zonated fat accumulation in a liver lobule. Therefore we developed a continuum biomechanical, tri-phasic, bi-scale, and multicomponent in silico model, which allows to numerically simulate coupled perfusion-function-growth interactions two-dimensionally in liver lobules. The developed homogenized model has the following specifications: (i) thermodynamically consistent, (ii) tri-phase model (tissue, fat, blood), (iii) penta-substances (glycogen, glucose, lactate, FFA, and oxygen), and (iv) bi-scale approach (lobule, cell). Our presented in silico model accounts for the mutual coupling between spatial and time-dependent liver perfusion, metabolic pathways and fat accumulation. The model thus allows the prediction of fat development in the liver lobule, depending on perfusion, oxygen and plasma concentration of free fatty acids (FFA), oxidative processes, the synthesis and the secretion of triglycerides (TGs). The use of a bi-scale approach allows in addition to focus on scale bridging processes. Thus, we will investigate how changes at the cellular scale affect perfusion at the lobular scale and vice versa. This allows to predict the zonation of fat distribution (periportal or pericentral) depending on initial conditions, as well as external and internal boundary value conditions.

代谢分区是指代谢功能沿肝脏正弦轴的空间分离。这种现象为调整肝脏代谢以满足健康和疾病的生理需求（例如，代谢功能障碍相关的脂肪肝病/MASLD）奠定了基础。分区代谢功能受到肝脏分区形态异常的影响，例如门静脉周围纤维化和中央周围脂肪变性。我们的目的是分析微灌注、氧梯度、脂肪代谢和肝小叶中分区脂肪积累之间的相互作用。因此，我们开发了一种连续体生物力学、三相、双尺度和多组分计算机模型，该模型可以对肝小叶中二维的灌注-功能-生长耦合相互作用进行数值模拟。开发的均质模型具有以下规格：(i) 热力学一致，(ii) 三相模型（组织、脂肪、血液），(iii) 五种物质（糖原、葡萄糖、乳酸、FFA 和氧气），以及(iv) 双尺度方法（小叶、细胞）。我们提出的计算机模型解释了空间和时间依赖性肝脏灌注、代谢途径和脂肪积累之间的相互耦合。因此，该模型可以根据灌注、氧气和游离脂肪酸 (FFA) 血浆浓度、氧化过程、甘油三酯 (TG) 的合成和分泌来预测肝小叶中的脂肪发育。双尺度方法的使用还允许关注尺度桥接过程。因此，我们将研究细胞尺度的变化如何影响小叶尺度的灌注，反之亦然。这允许根据初始条件以及外部和内部边界值条件来预测脂肪分布的分区（门静脉周围或中心周围）。