Circulating level of fatty acid-binding protein 4 is an independent predictor of metabolic dysfunction-associated fatty liver disease in middle-aged and elderly individuals

Abstract

Aims/introduction: Metabolic dysfunction-associated fatty liver disease (MAFLD), defined as hepatosteatosis with type 2 diabetes mellitus, overweight/obesity or metabolic dysregulation, has been proposed as a new feature of chronic liver disease. Fatty acid-binding protein 4 (FABP4) is expressed in adipose tissue, and secreted FABP4 is associated with the development of insulin resistance and atherosclerosis. However, the relationship between MAFLD and FABP4 has not been fully addressed.

Materials and methods: Associations of MAFLD with metabolic markers, including FABP4, fibroblast growth factor 21 and adiponectin, were investigated in 627 individuals (men/women 292/335) in the Tanno-Sobetsu Study, a population-based cohort.

Results: The mean age was 65 years (range 19-98 years, median [interquartile range] 68 [56-76] years). Hepatosteatosis was determined by the fatty liver index (FLI), and FLI ≥35 for men and FLI ≥16 for women were used for detection of fatty liver, as previously reported using 14,471 Japanese individuals. FLI was positively correlated with systolic blood pressure and levels of FABP4 (r = 0.331, P < 0.001), fibroblast growth factor 21, homeostasis model assessment of insulin resistance as an insulin resistance index and uric acid, and was negatively correlated with levels of high-density lipoprotein cholesterol and adiponectin. FABP4 concentration was independently associated with FLI after adjustment of age, sex, systolic blood pressure and levels of uric acid, high-density lipoprotein cholesterol, homeostasis model assessment of insulin resistance, adiponectin and fibroblast growth factor 21 in multivariable regression analysis. Logistic regression analysis showed that FABP4 was an independent predictor of MAFLD after adjustment of age, sex, presence of diabetes mellitus, hypertension and dyslipidemia, and levels of uric acid, homeostasis model assessment of insulin resistance, adiponectin and fibroblast growth factor 21.

Conclusions: FABP4 concentration is independently associated with FLI and is an independent predictor of MAFLD in middle-aged and elderly individuals.

Keywords: Adipokine; Fatty liver index; Hepatokine.

Figure 1

Correlations of fatty liver index (FLI) with metabolic parameters. (a). Logarithmically transformed (Log) fatty acid‐binding protein 4 (FABP4), (b) Log adiponectin and (c) Log fibroblast growth factor 21 (FGF21) were plotted against Log FLI in each participant (n = 627). Open circles and broken regression line: men (n = 292), closed circles and solid regression line: women (n = 335).

Figure 2

Comparisons of metabolic parameters in participants with and those without metabolic dysfunction‐associated fatty liver disease (MAFLD). (a) Comparisons of levels of fatty acid‐binding protein 4 (FABP4), (b) adiponectin and (c) fibroblast growth factor 21 (FGF21) shown by box plots in participants divided by the absence and presence of MAFLD into a non‐MAFLD group (n = 359, men/women 176/183) and MAFLD group (n = 268, men/women 116/152). *P < 0.05 versus non‐MAFLD.