Circulating levels of fatty acid-binding protein family and metabolic phenotype in the general population.

OBJECTIVE: Fatty acid-binding proteins (FABPs) are a family of 14-15-kDa proteins, and some FABPs have been to be used as biomarkers of tissue injury by leak from cells. However, recent studies have shown that FABPs can be secreted from cells into circulation. Here we examined determinants and roles of circulating FABPs in a general population. METHODS: From the database of the Tanno-Sobetsu Study, a study with a population-based cohort design, data in 2011 for 296 subjects on no medication were retrieved, and FABP1~5 in their serum samples were assayed. RESULTS: Level of FABP4, but not the other isoforms, showed a gender difference, being higher in females than in males. Levels of all FABPs were negatively correlated with estimated glomerular filtration rate (eGFR), but a distinct pattern of correlation with other clinical parameters was observed for each FABP isoform; significant correlates were alanine aminotransferase (ALT), blood pressure (BP), and brain natriuretic peptide (BNP) for FABP1, none besides eGFR for FABP2, age, BP, and BNP for FABP3, age, waist circumference (WC), BP, BNP, lipid variables, high-sensitivity C-reactive protein (hsCRP), and HOMA-R for FABP4, and age, WC, BP, ALT, BNP, and HOMA-R for FABP5. FABP4 is the most strongly related to metabolic markers among FABPs. In a multivariate regression analysis, FABP4 level was an independent predictor of HOMA-R after adjustment of age, gender, WC, BP, HDL cholesterol, and hsCRP. CONCLUSIONS: Each FABP isoform level showed a distinct pattern of correlation with clinical parameters, although levels of all FABPs were negatively determined by renal function. Circulating FABP4 appears to be a useful biomarker for detecting pre-clinical stage of metabolic syndrome, especially insulin resistance, in the general population

Multiple regression analysis for log FABPs.

<p>Multiple regression analysis for log FABPs.</p

Multiple regression analysis for log HOMA-R.

<p>Multiple regression analysis for log HOMA-R.</p

Correlation between urinary FABP4 and albuminuria.

<p>Logarithmically transformed urinary albumin-to-creatinine ratio (UACR) was plotted against logarithmically transformed urinary FABP4 (U-FABP4) for each subject with detectable U-FABP4 level (n = 299). There was a significant correlation between the two parameters (r = 0.360, p<0.001).</p

Simple and multiple regression analyses for log UACR (n = 392).

<p>FABP, fatty acid-binding protein; GFR, glomerular filtration rate; hsCRP, high-sensitivity C-reactive protein; UACR, urine albumin-to-creatinine ratio; NS, not selected.</p><p>Simple and multiple regression analyses for log UACR (n = 392).</p

Simple and multiple regression analyses for log U-FABP4 (n = 299).

<p>FABP, fatty acid-binding protein; GFR, glomerular filtration rate; hsCRP, high-sensitivity C-reactive protein; UACR, urine albumin-to-creatinine ratio; NS, not selected.</p><p>Simple and multiple regression analyses for log U-FABP4 (n  =  299).</p

Concentrations of FABPs.

<p>A. Bar graphs show serum concentrations of FABP1, FABP2, FABP3, FABP4, and FABP5 in male (n = 122) and female (n = 174) subjects on no medication. Values are presented as means ± SEM. *P<0.001. B. Log HOMA-R was plotted against log FABP4 in each study subject. There was a significant correlation between the two parameters (n = 296, r = 0.319, P<0.001). Open circle: male (n = 122), closed circle: female (n = 174).</p

Characteristics of the studied subjects.

<p>Variables are expressed as n or means ± SEM.</p>*<p>P<0.05,</p>**<p>P<0.01 vs. male.</p

Characteristics of the subjects with and without detectable U-FABP4.

<p>Variables are expressed as means ±SD, ^a number (%), or ^b medians (interquartile ranges).</p><p>FABP, fatty acid-binding protein; GFR, glomerular filtration rate; hsCRP, high-sensitivity C-reactive protein; UACR, urine albumin-to-creatinine ratio.</p><p>*P<0.05,</p><p>**P<0.01 vs. Undetectable FABP4.</p><p>Characteristics of the subjects with and without detectable U-FABP4.</p