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

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.