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.

Non‐alcoholic fatty liver disease and type 2 diabetes: An update

“…Elevated circulating AFABP level was associated with all the components of metabolic syndrome, including central obesity, insulin resistance, hypertension and atherogenic dyslipidemia, and was an independent predictor of the development of type 2 diabetes 52,53 . A high circulating AFABP level was also shown to be independently associated with ultrasound‐defined NAFLD in type 2 diabetes patients, as well as MAFLD based on the fatty liver index in a recent study of middle‐aged and elderly Japanese individuals 54,55 .…”

High fibrosis-4 index predicts the new onset of ischaemic heart disease during a 10-year period in a general population

“… 11 , 40 The fatty liver index (FLI) is a non-invasive marker calculated using body mass index, waist circumference and levels of γ-glutamyl transferase and triglycerides, and it has a high concordance with the histological criteria for NAFLD. 41 , 42 There have been several studies showing that the FLI is associated with the development of hypertension, 43 diabetes mellitus, 44 chronic kidney disease, 45 heart failure 46 and IHD 47 as well as fibroblast growth factor 21 (FGF21), a hepatokine, 48 and fatty acid binding-protein 4 (FABP4), 49 an atherogenic adipokine with possible therapeutic relevance. 50 , 51 On the contrary, NAFLD fibrosis score (NFS) is widely used to identify individuals with high probability of having advanced liver fibrosis and it is calculated by age, body mass index, presence of impaired fasting glucose or diabetes mellitus, and levels of AST, ALT, platelet count, and albumin.…”

Comment on a recent article titled “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”

“…To the Editor, In a recent issue of the Journal of Diabetes Investigation, Tanaka et al 1 reported valuable findings regarding the relationship of metabolic dysfunction-associated fatty liver disease (MAFLD) and fatty liver index (FLI) with fatty acid binding protein 4 (FABP4) in middle-aged and older adults. This study expanded the overall understanding of the association of hepatosteatosis with altered cytokine production and the independent predictors of MAFLD.…”