Introduction: Autotaxin (ATX) is an adipokine known to affect energy metabolism and lipid homeostasis. We aimed to evaluate serum ATX levels in metabolic-associated fatty liver disease (MAFLD) and other metabolic disorders in postmenopausal women. Methods: Postmenopausal women who received an annual health examination were included. The metabolic and demographic characteristics of the subjects were collected, including age, gender, weight, height, blood pressure, and biochemical parameters. Serum ATX level was determined by ELISA. Results: This cross-sectional includes 20 postmenopausal women and 20 age-paired healthy controls. MAFLD patients showed significant metabolic disturbance presented with increased body mass index (BMI), blood pressure (p < 0.001) and decreased high-density lipoprotein cholesterol (p < 0.05), as well as liver injury companied by elevated ALT (p < 0.05). Serum ATX levels were statistically higher in MAFLD (253.1 ± 52.1 vs. 202.2 ± 53.2 ng/mL; p < 0.01) and positively correlated with ALT (p < 0.001), γ-glutamyltransferase and BMI (p < 0.01), SBP and TG (p < 0.05). Higher ATX group demonstrated worsen metabolic states with greater proportion of MAFLD, higher BMI (p < 0.01), and ALT (p < 0.05). Logistic regression analysis revealed that serum ATX levels would positively independently predicted MAFLD (OR 1.049, 95% CI: 1.001–1.098, p < 0.05) with AUC of 0.763. Serum level of ATX is significantly elevated in hyperuricemia group (257.3 ± 60.9 vs. 214.5 ± 49.4 ng/mL; p < 0.05) and positively correlated with uric acid level (p < 0.01). Serum ATX would also act as diagnosing parameter of hyperuricemia with AUC of 0.706. Conclusions: Among postmenopausal women, serum ATX level is significantly elevated in MAFLD and related to multiple metabolic characteristics, especially hyperuricemia, which would thus serve as a potential noninvasive biomarker as well as a therapeutic target.

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