Circulating bone morphogenetic protein 9 as a new biomarker for non-invasive stratification of nonalcoholic fatty liver disease and metabolic syndrome

Nonalcoholic fatty liver disease (NAFLD) is closely related to metabolic syndrome (MetS). Bone morphogenetic protein 9 (BMP9) is an essential factor in glucose, lipid and energy metabolism. This study aims to investigate whether BMP9 can serve as a serological marker for the severity of NAFLD or MetS. Total of 263 individuals were enrolled and categorized into the healthy controls, NAFL group, and non-alcoholic steatohepatitis (NASH) at-risk group by the results of FibroTouch test and liver function. Basic demographic data and blood biochemical indicators were collected, and peripheral blood BMP9 levels were detected by enzyme-linked immunosorbent assay (ELISA). Stratified analysis of population BMP9 levels was conducted according to the number of MetS components. Serum BMP9 levels differentiated NASH at-risk (58.13 ± 2.82 ng/L) from the other groups: healthy control (70.32 ± 3.70 ng/L) and NAFL (64.34 ± 4.76 ng/L). ( p < 0.0001). The concentration of BMP9 was associated with transaminase, triglyceride (TG), fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), uric acid (UA). Controlled attenuation parameter of liver fat (CAP) and liver stiffness measurement (LSM) were negatively correlated with BMP9 levels, while high-density lipoprotein (HDL) levels were positively correlated. The risk of developing NAFLD increased along with elevated serum BMP9 and BMI, and a significantly higher risk observed in men compared to women. Additionally, serum BMP9 levels showed a downward trend as the number of components increased. BMP9 may be a protective factor for the onset and development of NAFLD, as well as a biomarker for the severity of the NAFLD and MetS.