Fatty Acid Binding Protein 4 Concentrations Research Articles

Maternal serum fatty acid binding protein-4 level is upregulated in fetal growth restriction with abnormal Doppler flow patterns.

This study aimed to determine fatty acid binding protein-4 (FABP-4) concentrations in maternal serum of fetal growth restriction (FGR) pregnancies and controls of normal pregnancies. Furthermore, we hypothesized that the alterations in FABP-4 levels might correlate with FGR severity. We performed this prospective case-control study with 83 pregnant women. The study groups included 26 FGR pregnancies without abnormal fetal Doppler flow patterns and 25 pregnancies complicated with FGR accompanied by abnormal fetal Doppler flow patterns. The median serum FABP-4 concentrations were significantly higher in the FGR cases with abnormal Doppler flow pattern group (2.09 ng/mL) than in the FGR cases without abnormal Doppler flow pattern group (1.62 ng/mL) and the control group (1.20 ng/mL, p < 0.001). A significant negative correlation was observed between maternal serum FABP-4 levels and time to birth from blood sample collection (r = -0.356 and p = 0.001), gestational week at birth (r = -0.386 and p < 0.001), and birth weight (r = -0.394 and p < 0.001). A 1.35 ng/mL cut-off value of serum FABP-4 level could be used to discriminate FGR cases with a 78.4% sensitivity and 60.6% specificity. The optimal cut-off value of FABP-4 levels as an indicator for the diagnosis of FGR with abnormal Doppler flow pattern was estimated to be 1.76 ng/mL, which yielded a sensitivity of 84.0% and a specificity of 75.8%. FABP-4 is a crucial biomarker in the diagnosis and determining the severity of pregnancies with restricted fetal growth. We consider that FABP-4 is a powerful, reliable, and unique biomarker to diagnose FGR pregnancies.

Abstract 15785: Effects of Empagliflozin on Fatty Acid Binding Protein 4 and Body Composition in Patients Without Diabetes but With Risk Factors for Adverse Cardiac Remodeling From the Empa-Heart 2 Cardiolink-7 Randomized Clinical Trial

Background: Prevention of the progression from stage B to C heart failure is an unmet need. Increased fat composition in skeletal muscle is one of the mechanisms associated with heart failure with preserved ejection fraction. Fatty acid binding protein 4 (FABP4) is known to facilitate the transport of fatty acid to tissue mitochondria for lipid oxidation. Knockdown of FABP4 gene is associated with increased body weight and fat mass in animal models. We sought to determine if Sodium-glucose co-transporter 2 (SGLT2) inhibition with empagliflozin leads to change in blood FABP4 levels and improvement in body composition in patients without diabetes and significant heart failure but with risk factors for adverse cardiac remodeling. Hypothesis: Empagliflozin increases blood FABP4 concentration and lowers body fat composition without changes in skeletal muscle mass. Methods: A total of 42 individuals between 40 and 80 years of age without diabetes but with risk factors for adverse cardiac remodeling were randomized to empagliflozin (10 mg/day; n=21) and placebo (n=21) groups for 6 months. Body composition parameters measured by bio-impedance analysis (InBody-720) included body weight (BW), skeletal muscle mass (SMM) and body fat mass (BFM) at baseline and 6 months follow up. Blood FABP4 concentrations were measured at the same time points. Results: There were no significant differences between two groups in baseline characteristics, BW, SMM, BFM, or FABP4. From baseline to 6 months, empagliflozin compared to placebo significantly increased blood FABP4 concentrations (6067.3 ± 7591.4 pg/ml vs 2714.9 ± 11232.6 pg/ml, p = 0.002), but decreased BW (-1.19 ± 1.01 kg vs 0.34 ± 2.59 kg, p = 0.018) and BFM (-0.68 ± 1.27 kg vs 0.53 ± 2.01 kg, p = 0.024). However, empagliflozin did not significantly affect changes in SMM from baseline to 6 months (-4.01 ± 0.70 kg vs -0.17 ± 0.96 kg, p = 0.387). Conclusions: SGLT2 inhibition with empagliflozin, in patients with neither diabetes nor significant heart failure but with risk factors for adverse cardiac remodeling, increased blood FABP4 concentrations and ameliorated BW and body fat composition with no effect on skeletal muscle mass following 6 months of treatment.

Elevated serum fatty acid-binding protein 4 level predicts all-cause and cardiovascular mortality in peritoneal dialysis patients: a five-year study

Background To explore the prospective role of serum fatty acid-binding protein 4 (FABP4) in the outcomes of peritoneal dialysis (PD) patients. Methods A prospective observational study was conducted with 159 patients on PD. Demographic and clinical data at baseline were collected from medical records. Biochemical data were recorded based on blood samples measured in a central laboratory. Serum FABP4 concentrations were determined using enzyme-linked immunosorbent assay. Body composition was measured using a Body Composition Monitor. Abdominal lateral plain radiography was used to evaluate vascular calcification. The primary endpoints were all-cause and cardiovascular death. Results The median of serum FABP4 concentration was 154.6 ng/mL (interquartile range, 132.8–269.7 ng/mL). Increased serum FABP4 was associated with increased vascular calcification proportion, time on dialysis, body mass index, high-sensitivity C-reactive protein (hs-CRP), intact parathyroid hormone (iPTH), triglycerides, body fat mass, and body fat percentage (p < 0.05). Increased serum FABP4 was associated with decreased residual kidney Kt/V urea (p < 0.05). Patients with hs-CRP≥ 3 mg/L had significantly higher serum FABP4 than those with hs-CRP< 3 mg/L (p < 0.05). Patients with vascular calcification had significantly higher serum FABP4 than those without vascular calcification (p < 0.05). During a median follow-up of 58.0 months, 58 all-cause deaths and 26 cardiovascular deaths occurred. High serum FABP4 levels were independently predictive for all-cause [hazard ratio (HR), 1.003; 95% confidence interval (CI), 1.001–1.005; p = 0.016] and cardiovascular death (HR, 1.005; 95% CI, 1.001–1.008; p = 0.006) in PD patients. Conclusions Increased serum FABP4 levels can independently predict all-cause and cardiovascular death in patients on PD.

Fatty acid binding protein 4 has prognostic value in peripheral artery disease

ObjectivePeripheral artery disease (PAD) remains undertreated, despite its association with major amputation and mortality. This is partly due to a lack of available disease biomarkers. The intracellular protein fatty acid binding protein 4 (FABP4) is implicated in diabetes, obesity, and metabolic syndrome. Given that these risk factors are strong contributors to vascular disease, we assessed the prognostic ability of FABP4 in predicting PAD-related adverse limb events. MethodsThis was a prospective case-control study with 3 years of follow-up. Baseline serum FABP4 concentrations were measured in patients with PAD (n = 569) and without PAD (n = 279). The primary outcome was major adverse limb event (MALE; defined as a composite of vascular intervention or major amputation). The secondary outcome was worsening PAD status (drop in ankle-brachial index ≥0.15). Kaplan-Meier and Cox proportional hazards analyses adjusted for baseline characteristics were conducted to assess the ability of FABP4 to predict MALE and worsening PAD status. ResultsPatients with PAD were older and more likely to have cardiovascular risk factors compared with those without PAD. Over the study period, MALE and worsening PAD status occurred in 162 (19%) and 92 (11%) patients, respectively. Higher FABP4 levels were significantly associated with 3-year MALE (unadjusted hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.04-1.27; adjusted HR, 1.18; 95% CI, 1.03-1.27; P = .022) and worsening PAD status (unadjusted HR, 1.18; 95% CI, 1.13-1.31; adjusted HR, 1.17; 95% CI, 1.12-1.28; P < .001). Three-year Kaplan-Meier survival analysis demonstrated that patients with high FABP4 levels had a decreased freedom from MALE (75% vs 88%; log rank = 22.6; P < .001), vascular intervention (77% vs 89%; log rank = 20.8; P < .001), and worsening PAD status (87% vs 91%; log rank = 6.16; P = .013). ConclusionsIndividuals with higher serum concentrations of FABP4 are more likely to develop PAD-related adverse limb events. FABP4 has prognostic value in risk-stratifying patients for further vascular evaluation and management.

Cord blood fatty acid binding protein 4 and lipids in infants born small- or large-for-gestational-age.

Adverse (poor or excessive) fetal growth "programs" an elevated risk of type 2 diabetes. Fatty acid binding protein 4 (FABP4) has been implicated in regulating insulin sensitivity and lipid metabolism relevant to fetal growth. We sought to determine whether FABP4 is associated with poor or excessive fetal growth and fetal lipids. In a nested case-control study in the Shanghai Birth Cohort including 60 trios of small-for-gestational-age (SGA, an indicator of poor fetal growth), large-for-gestational-age (LGA, an indicator of excessive fetal growth) and optimal-for-gestational-age (OGA, control) infants, we measured cord blood concentrations of FABP4 and lipids [high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterols, triglycerides (TG)]. Adjusting for maternal and neonatal characteristics, higher cord blood FABP4 concentrations were associated with a lower odds of SGA [OR = 0.29 (0.11-0.77) per log unit increment in FABP4, P = 0.01], but were not associated with LGA (P = 0.46). Cord blood FABP4 was positively correlated with both LDL (r = 0.29, P = 0.025) and HDL (r = 0.33, P = 0.01) in LGA infants only. FABP4 was inversely associated with the risk of SGA. The study is the first to demonstrate LGA-specific positive correlations of cord blood FABP4 with HDL and LDL cholesterols, suggesting a role of FABP4 in fetal lipid metabolism in subjects with excessive fetal growth.

Fatty acid-binding protein-4 (FABP4) and matrix metalloproteinase-9 (MMP9) as predictive values for nonalcoholic steatohepatitis (NASH)

BackgroundNonalcoholic fatty liver disease (NAFLD), especially nonalcoholic steatohepatitis (NASH) increases the risk for liver cirrhosis. Noninvasive tests for NAFLD/NASH exist, but they are unreliable and thus liver biopsy remains the standard for diagnosis and new noninvasive diagnostic approaches are of great interest. The aim of this study was to test whether the serum levels of fatty acid-binding protein-4 (FABP4) and matrix metalloproteinase-9 (MMP9) could be used as a diagnostic tool for NASH.MethodsPatients who underwent bariatric surgery and simultaneous liver biopsy were identified. Biopsies were assigned a NAFLD activity score (NAS). MMP9- and FABP4- Enzyme-linked Immunosorbent Assays (ELISAs) on serum samples were performed. The serum levels of FABP4/MMP9 were compared and different models to predict NASH were developed.ResultsA total of 84 patients were included, 28 patients (33.3%) were diagnosed with NASH. Higher concentrations of MMP9 in NASH patients (p < 0.01) were detected. FABP4 concentrations were not significantly increased. A moderate correlation between the NAS and MMP9 concentrations (r = 0.32, P < 0.01) was observed. The neural network model fit best with the dataset, with an area under the curve (AUC) of 83% and an accuracy of 88%.ConclusionSerum MMP9 levels are increased in patients with NASH and should routinely be measured in patients with obesity, but further investigations are needed to improve noninvasive NASH diagnosis.

A Notorious Trio! Inflammation, Metabolic Syndrome and Vitiligo.

There is evidence to support that vitiligo is linked to metabolic syndrome (MS), confirming its systemic nature. However, the underlying pathogenic mechanisms remain unknown. To reveal the possible association of MS with vitiligo. We also attempted to study the connection between some inflammatory markers and MS in vitiligo patients to evaluate their utility in predicting MS risk. The study included 100 vitiligo patients with an age range between 18 to 60 years and 100 controls with matched age, gender, and body mass index. All subjects were tested for MS components. Serum visceral adipose tissue-derived serine protease inhibitor (vaspin), fatty acid binding protein 4 (FABP4), vascular adhesion protein 1 (VAP-1), chitinase-3-like protein 1 (YKL-40), and high-sensitivity C-reactive protein (hs-CRP) were also measured. Regarding MS, it was observed in 22.0% of vitiligo patients and 2.0% of control subjects (P < 0.001). Serum FABP4, VAP-1, YKL-40, and hs-CRP concentrations were higher in patients than in the control group (P < 0.05 each), and their levels showed high sensitivity and specificity to differentiate MS when using the receiver operating characteristic (ROC). Levels of these markers, except serum vaspin, were significantly positively correlated with lipid profile markers (except high-density lipoprotein cholesterol) and fasting blood glucose levels (P < 0.05 each). MS was more common in vitiligo patients. The levels of the biomarkers studied were significantly higher in vitiligo patients. Furthermore, their levels accurately predicted MS in vitiligo patients. According to current research, these markers may be useful in assessing MS risk in vitiligo patients. Extensive research, however, is required.

Cushing's syndrome is associated with altered adipokine profile.

Adipokines are signaling molecules involved in the integration of metabolism. Changes in their concentrations were observed in obesity, metabolic syndrome, diabetes mellitus and cardiovascular diseases, as well as endocrine disorders. Cushing's syndrome is associated with metabolic dysregulation, but the significance of adipokines in this entity and related complications is largely unknown. The aim of our study was to determine the concentrations of adipokines: fetuin A, fatty acid binding protein 4 (FABP4) and retinol binding protein 4 (RBP4) in Cushing's syndrome and to assess their relation to established cardiovascular and diabetes risk markers. We examined 21 subjects with Cushing's syndrome and 24 healthy controls in a cross-sectional manner. Venous blood samples were analysed for adipokines, cortisol, adrenocorticotrophin, glucose, insulin, glycated haemoglobin (HbA1c), triglycerides, cholesterol fractions, thyrotropin and free thyroid hormones concentrations. Patients' body mass index (BMI) was evaluated, homeostatic model assessment-insulin resistance and Systematic Coronary Risk Evaluation (SCORE) were calculated. We found that the concentration of fetuin A was lower, while FABP4 and RBP4 concentrations were higher in Cushing's syndrome compared to controls [156.4 ± 60.0 µg/ml vs 260.7 ± 49.6 µg/ml; 79.8 (35.2-156.1) ng/ml vs 27.9 (17.1-36.7) ng/ml and 34 (30-37.7) mg/l vs 25.8 (23.6-27.7) mg/l, respectively]. Fetuin A correlated inversely, while FABP4 and RBP4 positively, with the concentrations of urinary free cortisol and adrenocorticotrophin. Fetuin A was positively related to LDL-cholesterol, and negatively to SCORE and HbA1c. FABP4 was associated positively with BMI, HbA1c and triglycerides, while RBP4 correlated positively with triglycerides and systolic blood pressure. Adipokines' concentrations change in hypercortisolism. Further research is needed to ascertain whether adipokines are involved in the development of metabolic complications accompanying Cushing's syndrome or secondarily reflect metabolic dysregulation.

Dynamics of FABP4 and CTRP3 biomarkers in patients with acute myocardial infarction and type 2 diabetes mellitus

The aim of the work was to study the characteristics of adipokine metabolism based on the analysis of fatty acid binding protein 4 (FABP4) and C1q/tumour necrosis factor-related protein-3 (CTRP3) levels and their dynamics in non-diabetic and diabetic patients with cardiovascular (CV) complications of acute myocardial infarction (AMI).&#x0D; Materials and methods. The study was carried out between 2018 and 2020 and involved 134 AMI patients with or without type 2 diabetes mellitus (DM) aged 59.00 [52.75; 66.00] years. The control group consisted of 20 healthy individuals with the mean age of 56.50 [48.50; 61.75] years. The serum levels of FABP4 and CTRP3 were measured by enzyme-linked immunosorbent assay on days 1 and 10 of hospital stay.&#x0D; Results. The mean levels of FABP4 were elevated on day 1 in AMI patients with type 2 DM (group II) compared to those in AMI patients (group I) and the control individuals (p&lt;0.05). The FABP4 concentrations on day 10 were 7.68 [6.42; 8.42] ng/ml and 8.31 [6.92; 9.63] ng/ml (p&lt;0.05) in groups I and II, respectively. The CTRP3 levels were lower in group II on day 1 as compared to those in group I and the control group patients (p&lt;0.001). After 10 days, the levels of CTRP3 were 287.56 [271.48; 300.58] ng/ml and 262.01 [225.32; 288.84] ng/ml) (p&lt;0.001) in groups I and II, respectively. In the presence of early AMI complications in diabetic patients, the levels of FABP4 remained elevated on day 10, and the levels of CTRP3 were low compared to those in diabetic patients without AMI complications (p&lt;0.05).&#x0D; Conclusions. The characteristics of adipokine metabolism in AMI patients have been revealed: the worsened imbalance in adipokine metabolism in type 2 DM due to the difference in FABP4 and CTRP3 levels. Special mention should be made of severely deteriorated adipokine metabolism in diabetic patients with CV complications

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.

ABSTRACTAims/IntroductionMetabolic 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 MethodsAssociations 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.ResultsThe 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.ConclusionsFABP4 concentration is independently associated with FLI and is an independent predictor of MAFLD in middle‐aged and elderly individuals.

Sex Dimorphic Associations of Gestational Diabetes Mellitus With Cord Plasma Fatty Acid Binding Protein 4 and Estradiol.

Fatty acid binding protein 4 (FABP4) has been associated with insulin resistance. Gestational diabetes mellitus (GDM) impairs fetal insulin sensitivity. Female newborns are more insulin resistant than male newborns. We sought to evaluate the association between GDM and cord blood FABP4, and explore potential sex dimorphic associations and the roles of sex hormones. This was a nested case-control study in the Shanghai Birth Cohort, including 153 pairs of newborns in GDM vs. euglycemic pregnancies matched by infant sex and gestational age at delivery. Cord plasma FABP4, leptin, total and high-molecular-weight adiponectin, testosterone and estradiol concentrations were measured. Adjusting for maternal and neonatal characteristics, cord plasma FABP4 (Mean ± SD: 27.0 ± 19.6 vs. 18.8 ± 9.6 ng/mL, P=0.045) and estradiol (52.0 ± 28.6 vs. 44.2 ± 26.6, ng/mL, P=0.005) concentrations were higher comparing GDM vs. euglycemic pregnancies in males, but similar in females (all P>0.5). Mediation analyses showed that the positive association between GDM and cord plasma FABP4 in males could be partly mediated by estradiol (P=0.03), but not by testosterone (P=0.72). Cord plasma FABP4 was positively correlated with total adiponectin in females (r=0.17, P=0.053), but the correlation was in the opposite direction in males (r=-0.11, P=0.16) (test for difference in r, P=0.02). Cord plasma FABP4 was not correlated with leptin in both sexes. The study is the first to demonstrate sex-dimorphic associations between GDM and cord plasma FABP4 or estradiol, and between FABP4 and adiponectin in newborns. GDM may affect fetal circulating FABP4 and estradiol levels in males only.

Risk of Gestational Diabetes Mellitus in relation to Plasma Concentrations of Fatty Acid-Binding Protein 4: A Nested Case-Control Study in China.

Objective The study is aimed at examining the effects of fatty acid-binding protein 4 (FABP4) on insulin resistance and gestational diabetes mellitus (GDM). Methods Based on a prospective birth cohort in Beijing, China, we conducted a nested case-control study and analyzed 135 GDM case-control pairs matched by age and the gestational week when they took the oral glucose tolerance test. We performed linear regression to analyze the association of plasma FABP4 concentrations with insulin resistance. We used logistic regression to estimate odds ratios (ORs) of FABP4 for GDM, controlling for potential confounders, including dietary intake and physical activity. Results Plasma FABP4 levels in the first and second trimesters were positively associated with fasting insulin and homeostasis model assessment for insulin resistance (HOMA-IR) in the second trimester (both P < 0.001). Compared with those in the lowest FABP4 tertile, women in the highest tertile of FABP4 levels in the first and second trimesters had 1.053 times (OR = 2.053, 95% CI 1.091 to 3.863) and 1.447 times (OR = 2.447, 95% CI 1.305 to 4.588) higher risk of developing GDM. Conclusions Elevated FABP4 levels in the first and second trimesters were associated with a higher level of insulin resistance and greater GDM risk, indicating FABP4 might predict women with high risk of developing GDM.

Detection of significantly high vitreous concentrations of fatty acid-binding protein 4 in patients with proliferative diabetic retinopathy

The fatty acid-binding protein4 (FABP4) and vascular endothelial growth factor A (VEGFA) play key roles in the metabolic and cardiovascular diseases, and proliferative diabetic retinopathy (PDR), respectively. To identify FABP4 in vitreous fluid in PDR, vitreous concentrations of FABP4 (V-FABP4) and VEGFA (V-VEGFA) from PDR (n = 20) and non-PDR (n = 20) patients were determined by Enzyme-Linked ImmunoSorbent Assays. The data, which included height and weight, systemic blood pressures, several blood biochemical parameters and blood flow at the optic nerve head (ONH) by laser speckle flowgraphy (LSFG) were collected. The levels of V-FABP4 and V-VEGFA were significantly higher in PDR patients than in non-PDR patients (P < 0.001) with a high positive correlation (r = 0.72, P < 0.001) between them. The findings were not affected by body mass index values and the presence of vitreous hemorrhaging. Among the clinical parameters, V-FABP4 correlated positively with creatinine and negatively with age and aspartate transaminase (AST) levels, while V-VEGFA correlated positively with fasting plasma glucose and hemoglobin A1c (HbA1c) levels but negatively with AST. Multiple regression analyses indicated that V-VEGFA, or V-FABP4, AST and HbA1c were independent predictors of V-FABP4 or V-VEGFA, respectively. Both were negatively correlated, but more evident in V-FABP4, with the ONH ocular blood flow.

Elevated circulating FABP4 concentration predicts cardiovascular death in a general population: a 12-year prospective study

Fatty acid-binding protein 4 (FABP4) is secreted from adipose tissue and acts as an adipokine, and an elevated circulating FABP4 level is associated with metabolic disorders and atherosclerosis. However, little is known about the causal link between circulating FABP4 level and mortality in a general population. We investigated the relationship between FABP4 concentration and mortality including cardiovascular death during a 12-year period in subjects of the Tanno-Sobetsu Study, a population-based cohort (n = 721, male/female: 302/419). FABP4 concentration at baseline was significantly higher in female subjects than in male subjects. All-cause death occurred in 123 (male/female: 74/49) subjects, and 34 (male/female: 20/14) and 42 (male/female: 26/16) subjects died of cardiovascular events and cancer, respectively. When divided into 3 groups according to tertiles of FABP4 level at baseline by sex (T1–T3), Kaplan–Meier survival curves showed that there were significant differences in rates of all-cause death and cardiovascular death, but not cancer death, among the groups. Multivariable Cox proportional hazard model analysis with a restricted cubic spline showed that hazard ratio (HR) for cardiovascular death, but not that for all-cause death, significantly increased with a higher FABP4 level at baseline after adjustment of age and sex. The risk of cardiovascular death after adjustment of age, sex, body mass index and levels of brain natriuretic peptide and high-sensitivity C-reactive protein in the 3rd tertile (T3) group (HR: 4.96, 95% confidence interval: 1.20–22.3) was significantly higher than that in the 1st tertile (T1) group as the reference. In conclusion, elevated circulating FABP4 concentration predicts cardiovascular death in a general population.

Differences in circulating fatty acid-binding protein 4 concentration in the venous and capillary blood immediately after acute exercise

BackgroundCirculating fatty acid-binding protein 4 (FABP4) is a marker for various diseases. It would be highly useful to have simple and less invasive techniques for the assessment of FABP4 concentrations in the clinical research setting. The purpose of the present study was to assess the concordance of circulating FABP4 concentrations in venous and capillary blood both at rest and immediately after acute exercise in healthy young males.ResultsThirty-eight healthy young male adults aged from 19 to 25 years (mean age, 20.8 ± 1.2 years) were recruited. Paired blood samples were taken from the cubital vein (venous) and fingertip (capillary) blood at rest (resting state) and immediately after incremental exercise (exercising state). Blood samples were analyzed to determine the circulating FABP4 concentration using an enzyme-linked immunosorbent assay. Pearson’s correlation coefficients for circulating FABP4 concentrations between venous and capillary blood samples indicated a strong positive correlation in both the resting and exercising state (resting state: r = 0.982, exercising state: r = 0.989, both p < 0.001). The mean FABP4 concentration was similar between venous and capillary blood in the resting state (p = 0.178), whereas it was significantly higher in capillary blood than in venous blood in the exercising state (p < 0.001). Furthermore, Bland–Altman plots showed a non-significant bias (− 0.07 ± 0.61 ng/mL, p = 0.453) in the resting state, whereas a significant bias (− 0.45 ± 0.61 ng/mL, p < 0.001) was observed in the exercising state.ConclusionsThese results indicate that capillary blood sampling can slightly overestimate circulating FABP4 concentrations under a physiologically dynamic state. However, the association between the venous and capillary blood in terms of FABP4 concentration was very strong, suggesting that capillary blood sampling can detect changes in FABP4 concentration in both physiologically steady and dynamic states.

Fatty-Acid-Binding Protein 4 as a Novel Contributor to Mononuclear Cell Activation and Endothelial Cell Dysfunction in Atherosclerosis

Background—Elevated circulating fatty-acid-binding protein 4 (FABP4) levels may be linked with cardiovascular events. This study aimed to investigate the mechanistic role of FABP4 in atherosclerosis. Methods—We recruited 22 patients with angiographically proven coronary artery disease (CAD) and 40 control subjects. Mononuclear cells (MNCs) and human coronary endothelial cells (HCAECs) were used for in vitro study. Results—Patients with CAD were predominantly male with an enhanced prevalence of hypertension, diabetes, and smoking history. FABP4 concentrations were up-regulated in culture supernatants of MNCs from CAD patients, which were positively correlated with the patients’ age, waist–hip ratio, body mass index, serum creatinine, type 2 diabetes, and the presence of hypertension. The adhesiveness of HCAECs to monocytic cells can be activated by FABP4, which was reversed by an FABP4 antibody. FABP4 blockade attenuated the oxidized low-density lipoprotein (oxLDL)-induced expression of ICAM-1, VCAM-1, and P-selectin. FABP4 impaired the tube formation and migration via the ERK/JNK/STAT-1 signaling pathway. FABP4 suppressed phosphorylation of eNOS and expression of SDF-1 protein, both of which can be reversed by treatment with VEGF. Blockade of FABP4 also improved the oxLDL-impaired cell function. Conclusion—We discovered a novel pathogenic role of FABP4 in MNC activation and endothelial dysfunction in atherosclerosis. FABP4 may be a therapeutic target for modulating atherosclerosis.

Comparison of plasma fatty acid binding protein 4 concentration in venous and capillary blood.

Circulating fatty acid binding protein 4 (FABP4) is associated with various diseases and simple and less invasive techniques for assessment of FABP4 concentration are required in clinical research setting. The purpose of the present study was to assess the correlation of plasma FABP4 concentration between venous and capillary blood in healthy young adults. Twenty-eight healthy young adults aged from 20 to 26 years (mean age, 22.2 ± 1.4 years, 14 males and 14 females) were included. Paired resting blood samples were taken from the cubital vein (venous) and fingertip (capillary) blood. Plasma FABP4 concentration in both blood was analyzed by enzyme-linked Immunosorbent assay. Plasma FABP4 concentration did not differ significantly between venous and capillary blood (−0.11± 0.75 ng/mL, p = 0.447, 95%CI: -0.402–0.182). Pearson’s correlation coefficient for plasma FABP4 concentration between venous and capillary blood samples suggests strong correlation (r = 0.961, p < 0.001). The Bland & Altman plot showed a non-significant bias (−0.11 ± 0.75 ng/mL, p = 0.684) and the 95% limits of agreement ranged from −1.59 to 1.37 ng/mL. FABP4 concentration in both venous and capillary blood was significantly higher in females than in males (venous blood: p = 0.041; capillary blood: p = 0.049). These results suggest that capillary blood sampling can detect gender difference and is useful for the assessment of FABP4 concentration.

P745Adipokines retinol binding protein 4 and fatty-acid binding protein 4 in left ventricular hypertrophy

Abstract Background and aim Obese individuals have a high risk of developing heart failure independent of concomitant diseases like diabetes mellitus or arterial hypertension. Hormones secreted by adipose tissue, so-called adipokines such as retinol binding protein 4 (RBP4) or fatty-acid binding protein 4 (FABP4), might constitute a link between obesity and cardiomyopathy. RBP4 is known to be associated with left ventricular hypertrophy, whereas FABP 4 has been reported to display anti- as well as pro-hypertrophic properties. Purpose The aim of the present study was to investigate the association of FABP4 and RBP4 with cardiac magnet resonance imaging (MRI) parameters. Methods We investigated plasma FABP4 and plasma RBP4 levels in 210 patients (70% men, mean age 63 years) who underwent an MRI examination and tested whether FAPB4 and RBP4 levels were associated with the following MRI parameters using linear cox regression: left ventricular end-diastolic diameter (LVEDD), interventricular septal (IVS) wall thickness, posterior wall thickness (PWT), relative wall thickness (RWT), left ventricular mass index (LVMI), and left ventricular ejection fraction (LVEF). An unadjusted model and a model adjusted for age, sex, body mass index, diabetes mellitus, arterial hypertension, smoking, presence of coronary artery disease, and heart rate were used. Results FABP4 levels were associated with higher PWT (p=0.0044, est. = 0.4) and RWT (p=0.0011, est. = 0.02). The associations were significant in the fully adjusted model (for PWT p=0.013, for RWT p=0.0043). We observed a non-linear, U-shaped relationship between FABP4 and LVEDD, RVEDD, and LVMI. FABP4 levels below the median were associated with lower LVEDD (p=0.0239, est. = −2.7), RVEDD (p=0.0127, est. = −3.3) and LVMI (p&lt;0.001, est. = −7.9). The association were significant in the fully adjusted model for LVMI only (p=0.0016). The associations between FABP4 levels above the median and LVEDD, RVEDD, and LVMI tended to be positive but were not statistically significant. In the unadjusted model, RBP4 was associated with higher IVS (p=0.005, est. = 0.59), PWT (p=0.0135, est. = 0.37), and RWT (p=0.036, est. = 0.02); these associations were not significant in the fully adjusted model. Interestingly, an interaction was observed between age and RBP4 in the association with IVS (p interaction = 0.01). Higher RBP4 and older age might have a stronger effect on IVS than age and RBP4 alone (see Figure). Conclusion Anti- and pro-hypertrophic associations between FABP4 and left ventricular size have been reported. Our results suggest that the pro- and anti-hypertrophic effects of FABP4 are dependent on FABP4 concentrations: lower FABP4 levels have an anti-hypertrophic effect, whereas higher levels have a pro-hypertrophic effect. RBP4 was associated with parameters of cardiac hypertrophy determined by MRI, suggesting a possible link between obesity and cardiomyopathy in an age dependent manner.

Plasma fatty acid-binding protein 4 (FABP4) level is associated with abnormal QTc interval in patients with stable angina and chronic kidney disease

BackgroundFatty acid-binding protein 4 (FABP4) (also known as adipocyte FABP or adipocyte P2) is expressed in adipocytes, macrophages, and capillary endothelial cells. Previous studies have shown associations among plasma FABP4, insulin resistance, metabolic syndrome, diabetes mellitus, greater coronary plaque burden, coronary artery disease, heart failure, and mortality. However, little is known about the relationship between FABP4 level and prolonged QT interval. The aim of this study was to investigate whether plasma FABP4 level is associated with a prolonged QT interval by analyzing 12-lead electrocardiograms (ECGs) in patients with stable angina and chronic kidney disease (CKD).MethodsThis study included 397 consecutive patients with stable angina and CKD who were enrolled in a disease management program. Plasma FABP4 concentrations were measured using enzyme-linked immunosorbent assays. A 12-lead ECG recording was obtained from each patient. We assessed the relationships between FABP4 levels (both as a continuous variable and stratified by tertile) at admission and corrected QT (QTc) prolongation.ResultsPatients with an abnormal QTc interval had higher median plasma FABP4 levels than those with borderline and normal QTc intervals (15.9 ng/mL vs. 10.2 ng/mL vs. 8.5 ng/mL, respectively, P < 0.0001). Statistically significant associations were observed between plasma FABP4 levels and QTc interval (β = 0.267, P < 0.0001). Using multivariate and trend analyses, a higher concentration of plasma FABP4 level was independently associated with QTc prolongation in patients with stable angina and CKD.ConclusionIn this study, plasma FABP4 levels were significantly higher in the patients with an abnormal QTc interval and were correlated with QTc prolongation. Further studies are required to elucidate whether plasma FABP4 plays a role in the pathogenesis of QTc prolongation.

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