Circulating Adipocyte–Fatty Acid Binding Protein Levels Predict the Development of the Metabolic Syndrome

Abstract

Background-Adipocyte-fatty acid binding protein (A-FABP), a major cytoplasmic protein in adipocytes, plays a central role in the development of diabetes and atherosclerotic cardiovascular disease in experimental animals. We have previously shown that A-FABP is present in the bloodstream and that its circulating levels correlate with metabolic risk factors in a cross-sectional study. In the present study, we further evaluated the prospective association of A-FABP with the metabolic syndrome (MetS) as defined by the updated National Cholesterol Education Program criteria. Methods and Results-In the present study, 495 nondiabetic adults from the population-based Hong Kong Cardiovascular Risk Factor Prevalence Study were prospectively followed up for 5 years. The relationship of serum A-FABP with the MetS and its components was investigated. At baseline, high A-FABP levels were associated with the MetS (odds ratio, 4.0; 95% CI, 1.5 to 10.4; highest versus lowest sex-specific tertile, adjusted for age, body mass index, the homeostasis model assessment index for insulin resistance, C-reactive protein, and adiponectin, Pϭ0.005). On long-term follow-up, subjects with higher baseline A-FABP levels had progressively worse cardiometabolic risk profile and increasing risk of the MetS. Among 376 subjects without the MetS at baseline, 50 had developed it at 5 years. Apart from the homeostasis model assessment index for insulin resistance (Pϭ0.001), baseline A-FABP was the only independent predictor of the development of the MetS during the 5-year follow-up (odds ratio, 4.7; 95% CI, 1.8 to 11.9; highest versus lowest sex-specific tertile, Pϭ0.001, adjusted for the homeostasis model assessment index for insulin resistance and body mass index). A-FABP was predictive of the MetS even after adjustment for each of its individual components. Conclusions-Circulating A-FABP predicts the development of the MetS independently of adiposity and insulin resistance.

Changes in serum adipocyte fatty acid‐binding protein in women with gestational diabetes mellitus and normal pregnant women during mid‐ and late pregnancy

“…Studies in animal models suggested that AFABP could be important in glucose homeostasis, and deletion of the AFABP gene protected mice from insulin resistance and hyperinsulinemia associated with both diet‐induced obesity7 and genetic obesity8. Higher baseline levels of circulating AFABP independently predicted the risk for developing metabolic syndrome during a follow up of 5 years9. Similarly, baseline AFABP concentrations were predictive of type 2 diabetes independent of obesity, insulin resistance or glycemic indices10 and as such, AFABP might play a central role in the development of type 2 diabetes and metabolic syndrome.…”

Metabolic and genetic predictors of circulating adipocyte fatty acid-binding protein

“…In accordance with this hypothesis, serum AFABP levels closely and positively correlate with AFABP expression in adipose tissue. 4 In this study, we present evidence that renal dysfunction is independently associated with higher AFABP serum levels. These results are in accordance with the hypothesis that renal elimination is a major route by which physiological AFABP serum levels are maintained similar to other adipokines.…”

“…Our findings that markers of obesity, including WtHR (Table 3), BMI, WHR, hip circumference, waist circumferences and percent body fat (data not shown), are independently associated with AFABP are consistent with recent data. Thus, Xu et al 4 demonstrate a direct independent correlation between baseline age-and gender-adjusted serum AFABP concentrations and BMI after 5-year follow-up in 495 non-diabetic adults. Furthermore, AFABP serum levels are associated with BMI in 67 non-obese and healthy subjects and 71 patients with the metabolic syndrome.…”

“…3 Elevated concentrations of circulating AFABP independently predicted the risk of developing a metabolic syndrome during a follow-up of 5 years in a study with 495 non-diabetic Chinese adults. 4 Furthermore, subjects with higher AFABP baseline serum levels showed a pronounced cardiometabolic risk profile. 4 High baseline AFABP serum levels also predicted the risk over 10 years to develop type 2 diabetes mellitus independent of obesity, IR and glycemic indices.…”

“…4 Furthermore, subjects with higher AFABP baseline serum levels showed a pronounced cardiometabolic risk profile. 4 High baseline AFABP serum levels also predicted the risk over 10 years to develop type 2 diabetes mellitus independent of obesity, IR and glycemic indices. 5 Moreover, serum AFABP levels positively correlated with carotid intima-media thickness (IMT) and the association remained significant in women after controlling for age, hypertension, dyslipidemia, hyperglycemia and C-reactive protein (CRP).…”