Bone morphogenetic protein 2 is a new molecular target linked to nonalcoholic fatty liver disease with potential value as non-invasive screening tool.
Authors:   Metabolic Syndrome and Vascular Risk Laboratory, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria del Hospital Universitario de La Princesa, Madrid, Spai., Marañón Patricia , Fernández-García Carlos Ernesto ,   Metabolic Syndrome and Vascular Risk Laboratory, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria del Hospital Universitario de La Princesa, Madrid, Spai., Isaza Stephania C ,   Metabolic Syndrome and Vascular Risk Laboratory, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria del Hospital Universitario de La Princesa, Madrid, Spai., Rey Esthe ,   Metabolic Syndrome and Vascular Risk Laboratory, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria del Hospital Universitario de La Princesa, Madrid, Spai., Gallego-Durán Rocío ,   SeLiver Group, Instituto de Biomedicina de Sevilla/CSIC/Hospital Virgen del Rocío; Sevilla, Spain.,   Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain., Montero-Vallejo Rocío ,   SeLiver Group, Instituto de Biomedicina de Sevilla/CSIC/Hospital Virgen del Rocío; Sevilla, Spain.,   Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain., Rodríguez de Cía Javier ,   Metabolic Syndrome and Vascular Risk Laboratory, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria del Hospital Universitario de La Princesa, Madrid, Spai., Ampuero Javier ,   SeLiver Group, Instituto de Biomedicina de Sevilla/CSIC/Hospital Virgen del Rocío; Sevilla, Spain.,   Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain., Romero-Gómez Manuel ,   SeLiver Group, Instituto de Biomedicina de Sevilla/CSIC/Hospital Virgen del Rocío; Sevilla, Spain.,   Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain., García-Monzón Carmelo ,   Metabolic Syndrome and Vascular Risk Laboratory, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria del Hospital Universitario de La Princesa, Madrid, Spai.,   Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain., González-Rodríguez Águeda ,   Metabolic Syndrome and Vascular Risk Laboratory, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria del Hospital Universitario de La Princesa, Madrid, Spai.,   Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain.
Published: June 2022

Background: Nonalcoholic fatty liver disease (NAFLD) is the commonest cause of chronic liver disease worldwide, being nonalcoholic 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. Methods: Hepatic and circulating levels of BMP2 were quantified in serum and liver specimens from 115 biopsyproven 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. Results: 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. Conclusion: 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.