Bone morphogenetic protein 2 is a new molecular target linked to non-alcoholic fatty liver disease with potential value as non-invasive screening tool

• Published in: Biomarker research Vol. 10; no. 1; p. 35
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 25.05.2022; BioMed Central; BMC
• Subjects: Algorithms; Apoptosis; Biopsy; BMP2; Bone morphogenetic protein 2; Bone morphogenetic proteins; Cell culture; Cholecystectomy; Fatty acids; Fatty liver; Gene expression; Hepatitis; Hepatocytes; Homeostasis; Hypertension; Inflammation; Insulin resistance; Laparoscopy; Liver diseases; Medical tests; Metabolism; Non-alcoholic fatty liver disease; Non-invasive diagnosis; Normal distribution; Palmitic acid; Proteins; Type 2 diabetes; Variables; Taiwan; Spain; United States > US; Madrid Spain; Germany; Bone morphogenetic proteins; BMP2; Non-invasive diagnosis; Hepatocytes; Non-alcoholic fatty liver disease
• ISSN: 2050-7771; 2050-7771
• 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.