Marañón Patricia, Fernández-García Carlos Ernesto, Isaza Stephania C, Rey Esther, Gallego-Durán Rocío, Montero-Vallejo Rocío, de Cía Javier Rodríguez, Ampuero Javier, Romero-Gómez Manuel, García-Monzón Carmelo, González-Rodríguez Águeda
Metabolic Syndrome and Vascular Risk Laboratory, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria del Hospital Universitario de La Princesa, C/Maestro Vives 2, 28009, Madrid, Spain.
SeLiver Group, Instituto de Biomedicina de Sevilla/CSIC/Hospital Virgen del Rocío, Sevilla, Spain.
Biomark Res. 2022 May 25;10(1):35. doi: 10.1186/s40364-022-00383-3.
Non-alcoholic fatty liver disease (NAFLD) is the commonest cause of chronic liver disease worldwide, being non-alcoholic steatohepatitis (NASH) its most clinically relevant form. Given the risks associated with taking a liver biopsy, the design of accurate non-invasive methods to identify NASH patients is of upmost importance. BMP2 plays a key role in metabolic homeostasis; however, little is known about its involvement in NAFLD onset and progression. This study aimed to elucidate the impact of BMP2 in NAFLD pathophysiology.
Hepatic and circulating levels of BMP2 were quantified in serum and liver specimens from 115 biopsy-proven NAFLD patients and 75 subjects with histologically normal liver (NL). In addition, BMP2 content and release was determined in cultured human hepatocytes upon palmitic acid (PA) overload.
We found that BMP2 expression was abnormally increased in livers from NAFLD patients than in subjects with NL and this was reflected in higher serum BMP2 levels. Notably, we observed that PA upregulated BMP2 expression and secretion by human hepatocytes. An algorithm based on serum BMP2 levels and clinically relevant variables to NAFLD showed an AUROC of 0.886 (95%CI, 0.83-0.94) to discriminate NASH. We used this algorithm to develop SAN (Screening Algorithm for NASH): a SAN < 0.2 implied a low risk and a SAN ≥ 0.6 indicated high risk of NASH diagnosis.
This proof-of-concept study shows BMP2 as a new molecular target linked to NAFLD and introduces SAN as a simple and efficient algorithm to screen individuals at risk for NASH.
非酒精性脂肪性肝病（NAFLD）是全球慢性肝病最常见的病因，非酒精性脂肪性肝炎（NASH）是其最具临床相关性的形式。鉴于肝活检存在风险，设计准确的非侵入性方法来识别NASH患者至关重要。骨形态发生蛋白2（BMP2）在代谢稳态中起关键作用；然而，其在NAFLD发生和发展中的作用知之甚少。本研究旨在阐明BMP2在NAFLD病理生理学中的影响。
对115例经活检证实的NAFLD患者和75例肝脏组织学正常（NL）的受试者的血清和肝脏标本中BMP2的肝脏和循环水平进行定量。此外，在棕榈酸（PA）过载的情况下，测定培养的人肝细胞中BMP2的含量和释放。
我们发现，NAFLD患者肝脏中BMP2的表达比NL受试者异常增加，这反映在血清BMP2水平升高。值得注意的是，我们观察到PA上调了人肝细胞中BMP2的表达和分泌。基于血清BMP2水平和与NAFLD临床相关变量的算法在鉴别NASH时的曲线下面积（AUROC）为0.886（95%可信区间，0.83 - 0.94）。我们使用该算法开发了NASH筛查算法（SAN）：SAN < 0.2表示低风险，SAN≥0.6表示NASH诊断的高风险。
这项概念验证研究表明BMP2是与NAFLD相关的新分子靶点，并引入SAN作为一种简单有效的算法来筛查有NASH风险的个体。
