Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, 3012 Bern, Switzerland.
Department for BioMedical Research, Hepatology, University of Bern, 3012 Bern, Switzerland.
Int J Mol Sci. 2022 Jul 28;23(15):8348. doi: 10.3390/ijms23158348.
The interaction between the mitochondria and the endoplasmic reticulum (ER) is essential for hepatocyte function. An increase in ER-mitochondria contacts (ERMCs) is associated with various metabolic diseases. Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and type 2 diabetes, and its progressive form non-alcoholic steatohepatitis (NASH) can lead to cirrhosis and hepatocellular carcinoma. However, the role of ERMCs in the progression of NAFL to NASH is still unclear. We assessed whether ERMCs could correlate with NAFLD severity. We used a proximity ligation assay to measure the abundance of ERMCs in liver biopsies from patients with biopsy-proven NAFLD ( = 48) and correlated the results with histological and metabolic syndrome (MetS) features. NAFLD patients were included according to inclusion and exclusion criteria, and then assigned to NAFL ( = 9) and NASH ( = 39) groups. ERMCs density could discriminate NASH from NAFL (sensitivity 61.5%, specificity 100%). ERMCs abundance correlated with hepatocellular ballooning. Moreover, the density of ERMCs increased with an increase in the number of MetS features. In conclusion, ERMCs increased from NAFL to NASH, in parallel with the number of MetS features, supporting a role for this interaction in the pathophysiology of NASH.
线粒体和内质网 (ER) 之间的相互作用对肝细胞功能至关重要。ER-线粒体接触 (ERMC) 的增加与各种代谢疾病有关。非酒精性脂肪性肝病 (NAFLD) 与肥胖和 2 型糖尿病有关，其进展形式非酒精性脂肪性肝炎 (NASH) 可导致肝硬化和肝细胞癌。然而，ERMC 在 NAFL 向 NASH 进展中的作用尚不清楚。我们评估了 ERMC 是否与 NAFLD 的严重程度相关。我们使用邻近连接测定法测量了经活检证实的 NAFLD 患者 ( = 48) 肝活检中 ERMC 的丰度，并将结果与组织学和代谢综合征 (MetS) 特征相关联。根据纳入和排除标准纳入 NAFLD 患者，然后将其分为 NAFL ( = 9) 和 NASH ( = 39) 组。ERMC 密度可区分 NASH 与 NAFL (敏感性 61.5%，特异性 100%)。ERMC 的丰度与肝细胞气球样变相关。此外，ERMC 的密度随着 MetS 特征数量的增加而增加。总之，从 NAFL 到 NASH，ERMC 增加，与 MetS 特征的数量平行，这支持了这种相互作用在 NASH 病理生理学中的作用。
