Fatty Acid Binding Protein 4 Concentrations Research Articles

1517-P: A Longitudinal Study of a Panel of Adipokines and Gestational Diabetes Risk

Prospective studies with measurement of a comprehensive panel of adipokines in early pregnancy and gestational diabetes (GDM) risk are sparse, and studies of adipokines for prediction of GDM are limited. We investigated a panel of adipokines in relation to GDM risk. In a nested case-control study within the NICHD Fetal Growth Studies-Singleton cohort (2009-2013), we identified 107 GDM cases and selected 214 controls matched on age, race/ethnicity, and gestational week (GW) at blood draw. Plasma Leptin, Soluble Leptin Receptor (sOB-R), Free Leptin, Chemerin, Fatty Acid Binding Protein 4 (FABP4), Retinol Binding Protein 4, Adiponectin, Omentin1, and Vaspin were measured prior to GDM at GWs 10-14, 15-26. Adjusting for maternal age, GW of blood collection, nulliparity, and family history of diabetes, conditional logistic analysis was performed to estimate adjusted odds ratios (aOR) for associations of adipokines with GDM. Receiver-operating-characteristic (ROC) curves assessed the predictive value of adipokines for GDM diagnosis. Leptin, Free Leptin, Chemerin, and FABP4 concentrations were significantly higher. Adiponectin, and sOB-R were significantly lower among cases than controls. At GW 10-14, Adiponectin, and sOB-R were significantly and inversely related to GDM risk. For example, across increasing quartiles of sOB-R the aOR were 1.00 (ref), 0.37 (0.19, 0.74), 0.28 (0.13, 0.59), and 0.24 (0.11, 0.52) (Ptrend≤.0001). In contrast, Leptin, Free Leptin, Chemerin, and FABP4 were significantly and positively associated with GDM risk. In general, associations of adipokines with GDM were stronger at GW 15-26. In addition, at GW 15-26, sOB-R significantly improved GDM prediction over conventional risk factors (age, GW, race, nulliparity, family history of diabetes, prepregnancy BMI) and glucose (P = 0.02). A panel of adipokines may be implicated in the pathogenesis of GDM with significant associations and incremental predictive value detected in early pregnancy before GDM is usually screened for. Disclosure E.C. Francis: None. M. Li: None. S. Hinkle: None. J. Chen: None. L. Chen: None. C. Zhang: None. Funding National Institutes of Health

A Longitudinal Study of a Panel of Adipokines and Gestational Diabetes Risk (OR36-01-19)

ObjectivesProspective studies with measurement of a comprehensive panel of adipokines in early pregnancy and gestational diabetes (GDM) risk are sparse, and studies of adipokines for prediction of GDM are limited. We aimed to prospectively investigate a comprehensive panel of adipokines in relation to GDM risk. MethodsWe investigated a panel of adipokines in relation to GDM risk. In a nested case-control study within the NICHD Fetal Growth Studies-Singleton cohort (2009–2013), we identified 107 GDM cases and selected 214 controls matched on age, race/ethnicity, and gestational week (GW) at blood draw. Plasma Leptin, Soluble Leptin Receptor (sOB-R), Free Leptin, Chemerin, Fatty Acid Binding Protein 4 (FABP4), Retinol Binding Protein 4, Adiponectin, Omentin1, and Vaspin were measured prior to GDM at GWs 10–14, 15–26. Adjusting for maternal age, GW of blood collection, nulliparity, and family history of diabetes, conditional logistic analysis was performed to estimate adjusted odds ratios (aOR) for associations of adipokines with GDM. Receiver-operating-characteristic (ROC) curves assessed the predictive value of adipokines for GDM diagnosis. ResultsBefore GDM diagnosis, Leptin, Free Leptin, Chemerin, and FABP4 concentrations were significantly higher, and Adiponectin, and sOB-R were lower among cases than controls. At GW 10–14, Adiponectin, and sOB-R were significantly and inversely related to GDM risk. For example, across increasing quartiles of sOB-R the aOR were 1.00 (ref), 0.37 (0.19, 0.74), 0.28 (0.13, 0.59), and 0.24 (0.11, 0.52) (Ptrend ≤ .0001). In contrast, Leptin, Free Leptin, Chemerin, and FABP4 were significantly and positively associated with GDM risk; Ptrend ≤ .0001, ≤.0001, 0.005, 0.004, respectively. In general, associations of adipokines with GDM were stronger at GW 15–26. In addition, at GW 15–26, sOB-R significantly improved GDM prediction over conventional risk factors (age, GW, race, nulliparity, family history of diabetes, prepregnancy BMI) and glucose (P = 0.02). ConclusionsA panel of adipokines may be implicated in the pathogenesis of GDM with significant associations and incremental predictive value detected in early pregnancy before GDM is usually screened for. Funding SourcesEllen Francis was supported by the Graduate Partnership Program in the Office of Intramural Training & Education, a component of the National Institutes of Health. Supporting Tables, Images and/or Graphs▪

Cord blood fatty acid-binding protein-4 levels are upregulated at both ends of the birthweight spectrum.

Fatty acid-binding protein-4 (FABP4) is an adipokine associated with obesity and signs of the metabolic syndrome. We aimed to investigate at birth in term neonates with normal and abnormal intrauterine growth concentrations of FABP4 and associate them with various perinatal parameters. Serum cord blood FABP4 levels were prospectively determined by ELISA in 80 singleton term appropriate-for-gestational-age (AGA), intrauterine growth-restricted (IUGR) and large-for-gestational-age (LGA) neonates. Compared to the AGA group, cord blood FABP4 levels were increased in the IUGR and LGA groups. Additionally, they were higher in early-term than full-term neonates. A significant U-shaped correlation was recorded between serum FABP4 levels and birthweight. A significant negative correlation between cord blood FABP4 and gestational age in the whole study population was noted. Cord blood FABP4 levels were significantly higher at the extremes of foetal growth at term and negatively correlated with gestational age, being increased in early-term versus full-term neonates. Further longitudinal studies with larger sample sizes are required to elucidate FABP4 implication in foetal growth and its association with future adverse cardiometabolic outcomes in the offspring.

Associations between Fatty Acid-Binding Protein 4⁻A Proinflammatory Adipokine and Insulin Resistance, Gestational and Type 2 Diabetes Mellitus.

There is ample scientific evidence to suggest a link between the fatty acid-binding protein 4 (FABP4) and insulin resistance, gestational (GDM), and type 2 (T2DM) diabetes mellitus. This novel proinflammatory adipokine is engaged in the regulation of lipid metabolism at the cellular level. The molecule takes part in lipid oxidation, the regulation of transcription as well as the synthesis of membranes. An involvement of FABP4 in the pathogenesis of obesity and insulin resistance seems to be mediated via FABP4-dependent peroxisome proliferator-activated receptor γ (PPARγ) inhibition. A considerable number of studies have shown that plasma concentrations of FABP4 is increased in obesity and T2DM, and that circulating FABP4 levels are correlated with certain clinical parameters, such as body mass index, insulin resistance, and dyslipidemia. Since plasma-circulating FABP4 has the potential to modulate the function of several types of cells, it appears to be of extreme interest to try to develop potential therapeutic strategies targeting the pathogenesis of metabolic diseases in this respect. In this manuscript, representing a detailed review of the literature on FABP4 and the abovementioned metabolic disorders, various mechanisms of the interaction of FABP4 with insulin signaling pathways are thoroughly discussed. Clinical aspects of insulin resistance in diabetic patients, including women diagnosed with GDM, are analyzed as well.

FABP4 in Gestational Diabetes-Association between Mothers and Offspring.

Fetuses exposed to gestational diabetes mellitus (GDM) have a higher risk of abnormal glucose homeostasis in later life. The molecular mechanisms of this phenomenon are still not fully understood. Fatty acid binding protein 4 (FABP4) appears to be one of the most probable candidates involved in the pathophysiology of GDM. The main aim of the study was to investigate whether umbilical cord serum FABP4 concentrations are altered in term neonates born to GDM mothers. Two groups of subjects were selected—28 healthy controls and 26 patients with GDM. FABP4, leptin, and ghrelin concentrations in the umbilical cord serum, maternal serum, and maternal urine were determined via an enzyme-linked immunosorbent assay. The umbilical cord serum FABP4 levels were higher in the GDM offspring and were directly associated with the maternal serum FABP4 and leptin levels, as well as the prepregnancy body mass index (BMI) and the BMI at and after delivery; however, they correlated negatively with birth weight and lipid parameters. In the multiple linear regression models, the umbilical cord serum FABP4 concentrations depended positively on the maternal serum FABP4 and negatively on the umbilical cord serum ghrelin levels and the high-density lipoprotein cholesterol. There are many maternal variables that can affect the level of FABP4 in the umbilical cord serum, thus, their evaluation requires further investigation.

Independent links between plasma xanthine oxidoreductase activity and levels of adipokines.

Aims/IntroductionXanthine oxidoreductase (XOR) is a rate‐limiting enzyme that catalyzes uric acid formation in the purine metabolism, is involved in an increase in reactive oxygen species. Plasma XOR activity has been shown to be associated with obesity, smoking, liver dysfunction, hyperuricemia, dyslipidemia and insulin resistance.Materials and MethodsThe association between plasma XOR activity, measured by using liquid chromatography and mass spectrometry, and levels of adipokines, including adiponectin, fatty acid‐binding protein 4 (FABP4) and fibroblast growth factor 21 (FGF21), was investigated in 282 participants (male/female: 126/156) of the Tanno‐Sobetsu Study who were not taking medication.ResultsWomen had lower plasma XOR activity than did men. Smoking habit was associated with increased activity. Plasma XOR activity was positively correlated with concentrations of FABP4 (r = 0.192, P < 0.001) and FGF21 (r = 0.208, P < 0.001), homeostasis model assessment of insulin resistance as an index of insulin resistance and uric acid, and was negatively correlated with adiponectin level (r = −0.243, P = 0.001). Multivariate regression analyses showed that levels of adiponectin, FABP4 and FGF21 were independent determinants of plasma XOR activity after adjusting age, sex, uric acid and homeostasis model assessment of insulin resistance. With additional adjustment of smoking habit, the level of FABP4, but not that of adiponectin or FGF21, remained as an independent predictor of plasma XOR activity.ConclusionsPlasma XOR activity was independently associated with levels of adipokines in a general population of individuals not taking medication.

Prediction of Circulating Adipokine Levels Based on Body Fat Compartments and Adipose Tissue Gene Expression

Background: Adipokines are hormones secreted from adipose tissue (AT), and a number of them have been established as risk factors for chronic diseases. However, it is not clear whether and to what extent adiposity, gene expression, and other factors determine their circulating levels. Objectives: To assess to what extent adiposity, as measured by the amount of subcutaneous AT (SAT) and visceral AT (VAT) using magnetic resonance imaging, and gene expression levels in SAT determine plasma concentrations of the adipokines adiponectin, leptin, soluble leptin receptor, resistin, interleukin 6, and fatty acid-binding protein 4 (FABP4). Methods: We performed a cross-sectional analysis of 156 participants from the EPIC Potsdam cohort study and analyzed multiple regression models and partial correlation coefficients. Results: For leptin and FABP4 concentrations, 81 and 45% variance were explained by SAT mass, VAT mass, and gene expression in SAT in multivariable regression models. For the remaining adipokines, AT mass and gene expression explained <16% variance of plasma concentrations. Gene expression in SAT was a less important predictor compared to AT mass. SAT mass was a better predictor than VAT mass for leptin (partial correlation r = 0.81, 95% confidence interval 0.75–0.86, vs. r = 0.58, 95% confidence interval 0.46–0.67), while differences between AT compartments were small for the other adipokines. Conclusions: While plasma levels of leptin and FABP4 can be explained in a large and medium part by the amount of AT and SAT gene expression, surprisingly, these predictors explained only little variance for all other investigated adipokines.

Fatty Acid-Binding Protein 4-An "Inauspicious" Adipokine-In Serum and Urine of Post-Partum Women with Excessive Gestational Weight Gain and Gestational Diabetes Mellitus.

The exact roles of adipokines in the pathogenesis of type 2 diabetes and obesity are still unclear. The aim of the study was to evaluate fatty acid binding protein 4 (FABP4) concentrations in the serum and urine of women with excessive gestational weight gain (EGWG) and gestational diabetes mellitus (GDM) in the early post-partum period, with reference to their laboratory test results, body composition, and hydration status. The study subjects were divided into three groups: 24 healthy controls, 24 mothers with EGWG, and 22 GDM patients. Maternal body composition and hydration status were evaluated by the bioelectrical impedance analysis (BIA) method. Concentrations of FABP4, leptin, and ghrelin were determined via enzyme-linked immunosorbent assay (ELISA). Healthy women were characterized by the lowest serum leptin concentrations and by a negative correlation between the serum and urine FABP4 levels. Serum FABP4 levels were the highest in the GDM group. Serum FABP4 and leptin concentrations correlated positively in the GDM group. The EGWG group had the highest degree of BIA disturbances in the early puerperium and positive correlations between the urine FABP4 and serum leptin and ghrelin concentrations. The physiological and pathological significance of these findings requires further elucidation.

Advances in Stroke 2017.

For stroke rehabilitation and recovery, 2017 was a year of reviews and research advances. Reviews included all aspects of poststroke rehabilitation and recovery. Cognitive rehabilitation for memory deficits was effective for memory improvements in the short term, but not in the long term.1 Circuit class therapy could improve mobility after stroke in a clinically meaningful way, even after 12 months poststroke.2 Electromechanical-assisted training for walking was most beneficial for subacute stroke survivors who were not ambulatory.3 Repetitive task training was effective regardless of the amount of task practice, type of intervention, or time since stroke.4 Physical activity training could positively affect poststroke cognition with small-to-moderate treatment effects that were apparent even in the chronic stroke phase.5 In all cases, more research was required to improve the quality of the findings, and a review of poststroke fatigue reported that the overall quality of the research was poor.6 Discovery research provided more insight into basic aspects of stroke rehabilitation and recovery. Stradecki-Cohan et al7 studied Sprague–Dawley rats subjected to 5 to 6 days of no (0 m/min), mild (6 m/min), moderate (10 m/min), or heavy (15–18 m/min) treadmill exercise 3 to 4 days poststroke and demonstrated that moderate exercise enhanced cognitive function for 1 week after exercise completion, independent of changes in physical fitness. Chang et al8 demonstrated that the number of Met alleles in brain-derived neurotrophic factor genotypes and corticospinal tract (CST) functional integrity may be independent predictors of upper extremity motor outcome 3 months poststroke. Tu et al9 found that concentrations of FABP4 (fatty acid–binding protein 4), an intracellular lipid chaperone involved in coordination of lipid transportation and atherogenesis, were a novel independent prognostic marker for poor functional outcome and mortality 3 months poststroke. Imaging of the CST also played a …

Knocking out or pharmaceutical inhibition of fatty acid binding protein 4 (FABP4) alleviates osteoarthritis induced by high-fat diet in mice

Adipokines play roles in the pathogenesis of osteoarthritis (OA). Fatty acid binding protein 4 (FABP4) is a novel adipokine that is closely associated with obesity and metabolic diseases. The aim of this study was to discover the potential role of FABP4 in OA. Seventy-two FABP4 knockout mice (KO) in C57BL/6N background and wild-type littermates (WT) (male, 6-week-old) were fed with a high-fat diet (HFD, 60% calorie) or standard diet (STD, 11.6% calorie) for 3 months, 6 months and 9 months (n=6 each). In the parallel study, forty-eight 6-week-old male WT mice were fed with HFD or STD, and simultaneously treated with daily oral gavage of selective FABP4 inhibitor BMS309403 (15mg/kg/d) or vehicle for 4 months and 6 months (n=6 each). Serum FABP4 and cartilage oligomeric matrix protein (COMP) concentration was quantified. Histological assessment of knee OA and micro-CT analysis of subchondral bone were performed. HFD induced obesity in mice. After 3 months and 6 months of HFD, KO mice showed alleviated cartilage degradation and synovitis, with significantly lower COMP, modified Mankin OA score, and MMP-13/ADAMTS4 expression. After 6 months and 9 months of HFD, KO mice showed less osteophyte formation and subchondral bone sclerosis. Chronic treatment of BMS309403 for 4 months and 6 months significantly alleviated cartilage degradation, but had no effects on the subchondral bone. Knocking out or pharmaceutical inhibition of FABP4 did not have significant effects on lean mice fed with STD. Knocking out or pharmaceutical inhibition of FABP4 alleviates OA induced by HFD in mice.

FABP4 as a biomarker for knee osteoarthritis.

To explore the role of an adipokine-termed fatty acid-binding protein 4 (FABP4) in osteoarthritis (OA). Patients with primary knee OA and non-OA controls were included. Paired tissues including plasma, synovial fluid (SF), subcutaneous fat and infrapatellar fat pad (IPFP) were harvested during surgery. FABP4 concentration was determined by ELISA. Plasma FABP4 increased significantly with OA stage (n=263). OA patients (n=38) had significantly higher plasma and SF FABP4 than non-OA patients (n=29). FABP4 level of IPFP was positively correlated with SF FABP4. OA patients had significantly high systemic and local FABP4, and IPFP may be the main source of FABP4 in synovial cavity. FABP4 may be a promising biomarker for OA.

Serum concentrations of fatty acid-binding protein 4 in Chinese children with type 1 diabetes mellitus

ObjectiveThe aim of this study was to test the serum concentrations of fatty acid-binding protein 4(FABP4) in children with type 1 diabetes mellitus (T1DM) and to determine the relationship between patients with good and poor glycaemic control who were classified according to their glycated hemoglobin A1c (HbA1c) levels. MethodsChildren with T1DM were selected consecutively from our department from May 2016 to May 2017. For comparison, the same non-diabetic, age, sex, BMI and pubertal stage-matched healthy children were selected consecutively among non-diabetic children. Serum levels of FABP4 were batch analyzed using a commercially available ELISA assay. Patients were categorized into two groups according to their glycaemic control (Poor glycaemic control is HbA1c>7.0% and good is ≤7.0%). ResultsIn this study, 118 children with T1DM and 118 control cases were included. The mean serum FABP4 concentrations were significantly (P<.001) higher in T1DM as compared to controls. There was a modest correlation between serum concentrations of FABP4 and duration of diabetes (r=0.484, P<.001). Fifty-two patients were defined as poor glycaemic control (HbA1c>7.0%). The mean serum FABP4 concentrations were significantly (P=.002) higher in the poor glycaemic control as compared to the good glycaemic control. After adjusting for all other predictors, FABP4 remained an independent poor glycaemic control indictor with an adjusted OR of 1.07 (95% CI, 1.01–1.13; P=.03). ConclusionsThe present results indicated that FABP4 concentrations were increased and independently associated with the poor glycaemic control in Chinese children with T1DM.

Circulating adipokines are associated with pre-eclampsia in women with type 1 diabetes.

The incidence of pre-eclampsia, a multisystem disorder of pregnancy, is fourfold higher in type 1 diabetic than non-diabetic women; it is also increased in women with features of the metabolic syndrome and insulin resistance. In a prospective study of pregnant women with type 1 diabetes, we measured plasma levels of adipokines known to be associated with insulin resistance: leptin, fatty acid binding protein 4 (FABP4), adiponectin (total and high molecular weight [HMW]; also known as high molecular mass), retinol binding protein 4 (RBP4) and resistin and evaluated associations with the subsequent development of pre-eclampsia. From an established prospective cohort of pregnant type 1 diabetic women, we studied 23 who developed pre-eclampsia and 24 who remained normotensive; for reference values we included 19 healthy non-diabetic normotensive pregnant women. Plasma adipokines were measured (by ELISA) in stored samples from three study visits (Visit 1- Visit 3) at different gestational ages (mean±SD): Visit 1, 12.4±1.8weeks; Visit 2, 21.7±1.4weeks; and Visit 3, 31.4±1.5weeks. All the women were free of microalbuminuria and hypertension at enrolment. All study visits preceded the clinical onset of pre-eclampsia. In all groups, leptin, the ratio of leptin to total or HMW adiponectin, FABP4 concentration, ratio of FABP4 to total or HMW adiponectin and resistin level increased, while total and HMW adiponectin decreased, with gestational age. At Visit 1: (1) in diabetic women with vs without subsequent pre-eclampsia, leptin, ratio of leptin to total or HMW adiponectin, and ratio of FABP4 to total or HMW adiponectin, were increased (p<0.05), while total adiponectin was decreased (p<0.05); and (2) in normotensive diabetic vs non-diabetic women, total adiponectin was elevated (p<0.05). At Visits 2 and 3: (1) the primary findings in the two diabetic groups persisted, and FABP4 also increased in women with subsequent pre-eclampsia (p<0.05); and (2) there were no differences between the two normotensive groups. By logistic regression analyses after covariate adjustment (HbA1c, insulin kg-1day-1 and gestational age), the best predictive models for pre-eclampsia were as follows: Visit 1, doubling of leptin, OR 9.0 (p<0.01); Visit 2, doubling of the leptin:total adiponectin ratio, OR 3.7 (p<0.05); and Visit 3, doubling of FABP4 concentration, OR 25.1 (p<0.01). The associations were independent of BMI. As early as the first trimester in type 1 diabetic women, adipokine profiles that suggest insulin resistance are associated with subsequent pre-eclampsia, possibly reflecting maternal characteristics that precede pregnancy. These associations persist in the second and third trimesters, and are independent of BMI. Insulin resistance may predispose women with type 1 diabetes to pre-eclampsia.

Serum fatty acid-binding protein 4 (FABP4) concentration is associated with insulin resistance in peripheral tissues, A clinical study.

Type 2 diabetes mellitus (T2DM) is caused by insulin resistance and β cell dysfunction. In recent studies reported that several markers associated with insulin sensitivity in skeletal muscle, Adiponectin and other parameters, such as fatty acid-binding protein (FABP4), have been reported to regulate insulin resistance, but it remains unclear which factor mostly affects insulin resistance in T2DM. In this cross-sectional study, we evaluated the relationships between several kinds of biomarkers and insulin resistance, and insulin secretion in T2DM and healthy controls. We recruited 30 participants (12 T2DM and 18 non-diabetic healthy controls). Participants underwent a meal tolerance test during which plasma glucose, insulin and serum C-peptide immunoreactivity were measured. We performed a hyperinsulinemic-euglycemic clamp and measured the glucose-disposal rate (GDR). The fasting serum levels of adiponectin, insulin-like growth factor-1, irisin, autotaxin, FABP4 and interleukin-6 were measured by ELISA. We found a strong negative correlation between FABP4 concentration and GDR in T2DM (r = -0.657, p = 0.020). FABP4 also was positively correlated with insulin secretion during the meal tolerance test in T2DM (IRI (120): r = 0.604, p = 0.038) and was positively related to the insulinogenic index in non-DM subjects (r = 0.536, p = 0.022). Autotaxin was also related to GDR. However, there was no relationship with insulin secretion. We found that serum FABP4 concentration were associated with insulin resistance and secretion in T2DM. This suggests that FABP4 may play an important role in glucose homeostasis.

Serum levels of fatty acid binding protein 4 and fat metabolic markers in relation to catecholamines following exercise

BackgroundLipolysis is stimulated by activation of adrenergic inputs to adipose tissues. Our recent study showed that serum concentrations of fatty acid binding protein 4 (FABP4) are robustly elevated in patients with acute myocardial infarction and ventricular tachyarrhythmia, that display a marked activation of the sympathetic nervous system (SNS). However, it remains unknown whether circulating FABP4 concentrations are associated with exercise-induced SNS activation. MethodsThirty one healthy volunteers underwent cardiopulmonary exercise testing on a cycle ergometer up to the workload levels below and above anaerobic threshold, low- and high-intensity exercise, respectively. Serial blood samplings were performed before and after exercise. ResultsHigh-intensity exercise significantly increased serum concentrations of FABP4 and catecholamines, and their concentrations declined fast thereafter in a similar fashion. These changes were accompanied by little, if any, changes in other metabolic markers. Regardless of adiposity, percent change from baseline to peak FABP4 levels (%FABP4) was comparable in all subjects. Stepwise regression analysis revealed that %FABP4 was highly correlated with that in norepinephrine. ConclusionsOur study reveals the significant correlation between circulating FABP4 and norepinephrine levels during exercise testing. Together with the fact that FABP4 is secreted from adipocytes via β-adrenergic-mediated lipolytic mechanisms, this study suggests FABP4 as a potential biomarker for adrenergic overdrive.

Circulating FABP4 (Fatty Acid–Binding Protein 4) Is a Novel Prognostic Biomarker in Patients With Acute Ischemic Stroke

FABP4 (fatty acid-binding protein 4) is an intracellular lipid chaperone involved in coordination of lipid transportation and atherogenesis. This study aimed at observing the effect of FABP4 on the 3-month outcomes in Chinese patients with acute ischemic stroke. In a prospective multicenter observational study, serum concentrations of FABP4 were on admission measured in plasma of 737 consecutive patients with acute ischemic stroke. Serum concentrations of FABP4, National Institutes of Health Stroke Scale score, and conventional risk factors were evaluated to determine their value to predict functional outcome and mortality within 3 months. During follow-up, an unfavorable functional outcome was found in 260 patients (35.3%), and 94 patients (12.8%) died. In multivariate models comparing the third and fourth quartiles to the first quartile of FABP4, the concentrations of FABP4 were associated with poor functional outcome and mortality. Compared with the reference category (Q1-Q3), the concentrations of FABP4 in Q4 had a relative risk of 4.77 (95% confidence interval [CI], 2.02-8.15; P<0.001) for poor functional outcome and mortality (odds ratio, 6.15; 95% CI, 3.43-12.68) after adjusting for other significant outcome predictors in univariate logistic regression analysis. Receiver-operating characteristic curves to predict poor functional outcome and mortality demonstrated areas under the curve of FABP4 of 0.78 (95% CI, 0.75-0.82) and 0.83 (95% CI, 0.79-0.88), which improved the prognostic accuracy of National Institutes of Health Stroke Scale score with combined areas under the curve of 0.83 (95% CI, 0.76-0.89; P<0.01) and 0.86 (95% CI, 0.81-0.92), respectively. Data show that FABP4 is a novel independent prognostic marker improving the currently used risk stratification of stroke patients.

Serum FABP5 concentration is a potential biomarker for residual risk of atherosclerosis in relation to cholesterol efflux from macrophages

Cholesterol efflux capacity (CEC) from macrophages, the first step in the reverse cholesterol transport pathway, is inversely associated with residual risk for atherosclerotic cardiovascular disease. Fatty acid-binding protein 4 (FABP4) and FABP5 are expressed in both adipocytes and macrophages and play significant roles in the development of insulin resistance and atherosclerosis. Both FABP4 and FABP5 are secreted from cells, and their circulating levels are associated with insulin resistance and atherosclerosis. We investigated the association between CEC and levels of FABP4 and FABP5 in 250 subjects without any medications. CEC was positively correlated with HDL cholesterol level and negatively correlated with concentrations of high-sensitivity C-reactive protein (hsCRP) and FABP5, but not FABP4. Multiple regression analysis demonstrated that FABP5 concentration was an independent predictor of CEC after adjustment of age, gender and levels of HDL cholesterol and hsCRP. In 129 of the 250 subjects who underwent carotid ultrasonography, mean intima-media thickness was negatively correlated with CEC and was positively correlated with concentrations of FABP4 and FABP5. In conclusion, in contrast to FABP4, circulating FABP5 is associated with decreased CEC and carotid atherosclerosis, suggesting that FABP5 level is a regulatory factor of CEC and a potential biomarker for residual risk of atherosclerosis.

Abstract 13049: Serum FABP5 Concentration, a Novel Determinant of Cholesterol Efflux From Macrophages, is a Potential Biomarker for Residual Risk of Atherosclerosis

Introduction: Cholesterol efflux capacity (CEC) from macrophages, represents the reverse cholesterol transport pathway, is inversely associated with risk for atherosclerotic cardiovascular disease. Fatty acid-binding protein 4 (FABP4) and 5 (FABP5) are expressed in both adipocytes and macrophages and play significant roles in the development of insulin resistance and atherosclerosis. FABP4 and FABP5 have been shown to be secreted from cells, and the circulating levels are associated with insulin resistance and atherosclerosis. Hypothesis: Serum levels of FABP4 and FABP5 are independently associated with CEC. Methods: A total of 250 subjects who were not on medication were recruited from subjects of the Tanno-Sobetsu Study, a study with a population-based cohort design. Concentrations of FABP4 and FABP5 were measured using commercially available enzyme-linked immunosorbent assay kits. CEC was measured using apolipoprotein B-depleted serum and J774.1 cells, a murine macrophage cell line. Results: CEC was positively correlated with HDL cholesterol and was negatively correlated with concentrations of high-sensitivity C-reactive protein (hsCRP) and FABP5 (r = -0.180, P = 0.041) but not with FABP4 level. Multiple regression analysis demonstrated that FABP5 level was an independent predictor of CEC after adjustment of age, gender and levels of HDL cholesterol and hsCRP. In 129 out of 250 subjects who underwent carotid ultrasonography, mean intima-media thickness was negatively correlated with CEC (r = -0.248, P = 0.005) and was positively correlated with concentrations of FABP4 (r = 0.178, P = 0.043) and FABP5 (r = 0.194, P = 0.028). Conclusions: In contrast to FABP4, FABP5 is independently associated with both carotid atherosclerosis and decreased CEC, suggesting that FABP5 level is a novel regulatory factor of CEC and a potential biomarker for residual risk of atherosclerosis in relation to cholesterol efflux from macrophages.

Implications of circulating irisin and Fabp4 levels in patients with polycystic ovary syndrome

abstractThe aim of the study was to evaluate the fatty acid-binding protein-4 (FABP4) and irisin concentrations in women with polycystic ovary syndrome (PCOS). Forty-nine women with PCOS, diagnosed according to Rotterdam criteria and 39 healthy women matched for body mass index (BMI) and age. Serum irisin and plasma FABP4 concentrations were measured in both groups. The association of irisin and FABP4 concentrations with metabolic parameters were also tested. Women with PCOS had significantly lower mean serum irisin concentrations than control subjects (158.5 ± 123.3 versus 222.9 ± 152.2 ng/ml, p < 0.05). Concentrations of FABP4 in PCOS and control groups were not significantly different (10.5 ± 4.4 versus 10.9 ± 4.2 ng/ml, p > 0.05). FABP4 concentrations were correlated with BMI, waist–hip ratio (WHR) and HOMA-IR (r = 0.57, p = 0.001; r = 0.26, p = 0.03; r = 0.26, p = 0.03, respectively). No associations between irisin and all the others parameters except serum levels of LH were found. Serum irisin concentrations of women with PCOS were lower compared to the controls. Moreover, there were no difference in plasma FABP4 concentrations between women with PCOS and controls.

Plasma fatty acid-binding protein 4 (FABP4) as a novel biomarker to predict gestational diabetes mellitus.

Fatty acid-binding protein 4 (FABP4) is mainly expressed in adipocytes and macrophages and is demonstrated to be elevated in diabetes patients. The aim of this study was to evaluate the possible role of FABP4 in the diagnosis of GDM and to investigate the relationship between FABP4 and overweight, insulin resistance and inflammatory marker TNF-α. A total of 46 women with GDM and 55 age-matched pregnant women without GDM (non-GDM) were eligible for the study. Demographic and biochemical parameters and fasting venous blood samples of two groups were collected from all cases. Serum concentrations of FABP4 were determined using enzyme-linked immunosorbent assay (ELISA). The predictive value of Serum FABP4 level was evaluated using receiver operating characteristic curve (ROC curve) analysis. We found that the serum FABP4 levels were significantly higher in GDM compared to the non-GDM group. The area under the ROC curve assay yielded a satisfactory result of 0.94 (95% confidence interval 0.90-0.98; p<0.001). The best compromise between 86.96% specificity and 89.09% sensitivity was obtained with a cutoff value of 1.96ng/mL for GDM diagnosis. Moreover, a significant positive correlation was observed between FABP4 and overweight, insulin resistance and TNF-α in pregnant women with GDM. These results suggest that serum FABP4 may potentially serve as a novel biomarker for the prediction of GDM.