Associations among serum FGF21 levels, inflammation, and metabolic dysfunction-associated steatotic liver disease: mediation analyses in a Chinese community-based population

Abstract

Objective: This study aimed to explore the relationship between serum fibroblast growth factor 21 (FGF21) levels and metabolic dysfunction-associated steatotic liver disease (MASLD), and further explore the mediation effect of inflammation in their association. Methods: This study included 1,710 community residents, including 697 men and 1,013 women, with a median age of 59 (55–63) years. Abdominal ultrasound was used to detect the liver and calculate liver fat content (LFC). MASLD was diagnosed according to the 2023 Delphi consensus. Serum FGF21 levels were measured using enzyme-linked immunosorbent assay. Inflammation levels were assessed through C-reactive protein (CRP), white blood cells (WBCs), and tumor necrosis factor-α (TNF-α). Results: Regardless of overweight/obese status, serum FGF21 levels were higher in individuals with MASLD than in individuals without MASLD (all P < 0.05). In the multivariate logistic regression model, for every 1-unit increase in serum FGF21 levels, the risk of MASLD was 1.46 (95% confidence interval (CI), 1.11–1.92) and 1.51 (95% CI, 1.19–1.93) in lean and overweight/obesity subjects, respectively. Moreover, serum FGF21 levels were positively correlated with LFC (P < 0.05), and the relationship between serum FGF21 and LFC could be partially mediated by CRP, WBC, and TNF-α. Conclusions: Regardless of overweight/obese status, serum FGF21 levels were significantly associated with an elevated risk of MASLD. Furthermore, serum FGF21 levels were independently associated with LFC, which could be partially mediated by inflammation.