Epidermal fatty-acid-binding protein: a new circulating biomarker associated with cardio-metabolic risk factors and carotid atherosclerosis.

AIMS: Epidermal fatty-acid-binding protein (E-FABP) is highly homologous to adipocyte FABP (A-FABP), which mediates obesity-related metabolic syndrome (MetS), diabetes and atherosclerosis in animals. Combined deficiency of E-FABP and A-FABP protects against the MetS and atherosclerosis in mice. This study investigated the association of serum E-FABP with cardio-metabolic risk factors and carotid atherosclerosis in humans. METHODS AND RESULTS: The presence of E-FABP in human plasma was detected by tandem mass spectrometry. Serum E-FABP levels, determined by an enzyme-linked immunosorbent assay in 479 Chinese subjects (age: 55.4 ± 13.5 years; M/F: 232/247), correlated positively (P < 0.05 to <0.001, age-adjusted) with parameters of adiposity, adverse lipid profiles, serum insulin, A-FABP, and C-reactive protein levels and were higher in subjects with the MetS (P < 0.001 vs. no MetS). The association of E-FABP with the MetS was independent of A-FABP. Furthermore, serum E-FABP correlated with carotid intima-media thickness (IMT; P < 0.001) and was independently associated with carotid IMT in men (adjusted P = 0.03). CONCLUSION: E-FABP is a new circulating biomarker associated with increased cardio-metabolic risk. It may contribute to the development of the MetS and carotid atherosclerosis in humans, independent of the effect of A-FABP.

Circulating adipocyte-fatty acid binding protein levels predict the development of the metabolic syndrome: a 5-year prospective study.

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, P=0.005). 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 (P=0.001), 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, P=0.001, 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.

Serum zinc-alpha2-glycoprotein correlates with adiposity, triglycerides, and the key components of the metabolic syndrome in Chinese subjects.

CONTEXT: Zinc-alpha2-glycoprotein (ZAG) is a 40-kDa circulating glycoprotein secreted from the liver and adipose tissues. Animal studies have demonstrated the role of ZAG as a lipid-mobilizing factor involved in regulating lipid metabolism and adiposity. However, the clinical relevance of these findings remains to be established. OBJECTIVE: This study aimed to address the relationship of serum ZAG levels with adiposity and cardiometabolic risk factors in humans. DESIGN AND SETTING: A total of 258 Chinese subjects [aged 55.1 +/- 12.5 yr; 120 males, 138 females; body mass index (BMI), 25.4 +/- 4.1 kg/m(2)] were randomly selected from the population-based Hong Kong Cardiovascular Risk Factor Prevalence Study, based on their BMI. Serum ZAG levels were determined with ELISA. The relationship between serum ZAG levels and cardiometabolic parameters was assessed. RESULTS: Serum ZAG levels were higher in men (P < 0.001 vs. women). Serum ZAG correlated positively with age, parameters of adiposity (waist circumference and BMI), fasting insulin, insulin resistance indices, serum triglycerides, adipocyte-fatty acid-binding protein, and C-reactive protein, and diastolic blood pressure (all P < 0.005, age- and sex-adjusted), and inversely with high-density lipoprotein-cholesterol levels (P = 0.008, age- and sex-adjusted). It was also elevated progressively with an increasing number of components of the metabolic syndrome (P for trend < 0.001). On multivariate analysis, serum ZAG was independently associated with male sex, the metabolic syndrome (or type 2 diabetes and serum triglycerides), and C-reactive protein (all P

Circulating levels of adipocyte and epidermal fatty acid-binding proteins in relation to nephropathy staging and macrovascular complications in type 2 diabetic patients.

OBJECTIVE: To investigate the relationships of serum adipocyte fatty acid-binding protein (A-FABP) and epidermal fatty acid-binding protein (E-FABP) with renal dysfunction and macrovascular complications in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: The associations of serum A-FABP and E-FABP with markers of renal function, nephropathy staging, and macrovascular complications were examined in 237 type 2 diabetic patients. RESULTS: Serum A-FABP and E-FABP correlated significantly with serum creatinine, mean albumin excretion rate, and glomerular filtration rate (all P < 0.001) and were independently associated with diabetic nephropathy staging (P = 0.001 and P < 0.05, respectively). Circulating levels of both types of FABP were increased (P < 0.01) in subjects with macrovascular complications. Serum A-FABP was independently associated with macrovascular complications (odds ratio 2.92 [95% CI 1.42-6.01]; P = 0.004). CONCLUSIONS: Serum A-FABP and E-FABP might be novel serum biomarkers for evaluating the progression of nephropathy and its cardiovascular risk in type 2 diabetic patients.

Serum FGF21 levels are increased in obesity and are independently associated with the metabolic syndrome in humans.

OBJECTIVE: Fibroblast growth factor 21 (FGF21) is a metabolic regulator with multiple beneficial effects on glucose homeostasis and insulin sensitivity in animal models. This study aimed to investigate the relationship between its serum levels and various cardiometabolic parameters in humans. RESEARCH DESIGN AND METHODS: A newly developed immunoassay was used to measure serum FGF21 levels in 232 Chinese subjects recruited from our previous cross-sectional studies. The mRNA expression levels of FGF21 in the liver and adipose tissues were quantified by real-time PCR. RESULTS: Serum FGF21 levels in overweight/obese subjects were significantly higher than in lean individuals. Serum FGF21 correlated positively with adiposity, fasting insulin, and triglycerides but negatively with HDL cholesterol, after adjusting for age and BMI. Logistic regression analysis demonstrated an independent association between serum FGF21 and the metabolic syndrome. Furthermore, the increased risk of the metabolic syndrome associated with high serum FGF21 was over and above the effects of individual components of the metabolic syndrome. Our in vitro study detected a differentiation-dependent expression of FGF21 in 3T3-L1 adipocytes and human adipocytes. In db/db obese mice, FGF21 mRNA expression was markedly increased in both the liver and adipose tissue compared with that in their lean littermates. Furthermore, FGF21 expression in subcutaneous fat correlated well with its circulating concentrations in humans. CONCLUSIONS: FGF21 is a novel adipokine associated with obesity-related metabolic complications in humans. The paradoxical increase of serum FGF21 in obese individuals, which may be explained by a compensatory response or resistance to FGF21, warrants further investigation.