Serum FABP4 Research Articles

Urinary excretion of fatty acid-binding protein 4 is associated with albuminuria and renal dysfunction.

BackgroundFatty acid-binding protein 4 (FABP4/A-FABP/aP2) is expressed in not only adipocytes and macrophages but also peritubular capillaries in the normal kidney. We recently demonstrated that ectopic expression of FABP4, but not FABP1 known as liver FABP (L-FABP), in the glomerulus is associated with progression of proteinuria and renal dysfunction. However, urinary excretion of FABP4 has not been investigated.MethodsSubjects who participated in the Tanno-Sobetsu Study, a study with a population-based cohort design, in 2011 (n = 392, male/female: 166/226) were enrolled. Urinary FABP4 (U-FABP4) and urinary albumin-to-creatinine ratio (UACR) were measured. Change in estimated glomerular filtration rate (eGFR) was followed up one year later.ResultsIn 93 (23.7%) of the 392 subjects, U-FABP4 level was below the sensitivity of the assay. Subjects with undetectable U-FABP4 were younger and had lower UACR and higher eGFR levels than subjects with measurable U-FABP4. U-FABP4 level was positively correlated with age, systolic blood pressure and levels of serum FABP4 (S-FABP4), triglycerides, hemoglobin A1c (HbA1c), urinary FABP1 (U-FABP1) and UACR (r = 0.360, p<0.001). Age, S-FABP4, U-FABP1 and UACR were independent predictors of U-FABP4. On the other hand, systolic blood pressure, HbA1c and U-FABP4 were independently correlated with UACR. Reduction in eGFR after one year was significantly larger in a group with the highest tertile of baseline U-FABP4 than a group with the lowest tertile.ConclusionsUrinary FABP4 level is independently correlated with level of albuminuria and possibly predicts yearly decline of eGFR. U-FABP4 would be a novel biomarker of glomerular damage.

The levels of adipocyte protein, a transporter of fatty acids, and adiponectin in the adolescents presenting with obesity and their relationship with the distribution of the adipose tissue

This study included 130 patients at the age of 14-17 years presenting with constitutional exogenous obesity (CEO) and 24 children without obesity (controls). The levels of adipocyte protein, a transporter of fatty acids (FABP4), in the sera of the adolescents with CEO were significantly higher than in the absence of obesity. They did not depend on the stage of puberty and differed in the children of different sex. The serum adiponectin level in the boys showed negative correlation with the amount of visceral adipose tissue and decreased progressively with the increase in the degree of obesity. The rise in the serum FABP4 level in the girls was associated with the increase in the amount of subcutaneous adipose tissue and positively correlated with the severity of obesity. Visceral obesity in the adolescents was accompanied by a variety of metabolic disorders while changes in the waist circumference did not reflect dynamics in the amount of visceral adipose tissue.

Fabp4, a new player in the adipo-pancreatic axis.

Fabp4, a new player in the adipo-pancreatic axis.

Abstract 389: Elevation of Fatty Acid-Binding Protein 4 is Associated with Left Ventricular Hypertrophy and Diastolic Dysfunction in a General Population

Fatty acid-binding protein 4 (FABP4/A-FABP/aP2) is expressed in both adipocytes and macrophages. Recent studies have shown secretion of FABP4 from adipocytes and association of elevated serum FABP4 level with obesity, insulin resistance, hypertension, and atherosclerosis. However, little is known about role of FABP4 in cardiac function. From database of the Tanno-Sobetsu Study, a study with prospective population-based cohort design, all data from female subjects who were on no medication and underwent echocardiography in 2011 (n = 108) were retrieved for analyses of relationships between serum FABP4 concentration, metabolic markers and parameters of echocardiography. FABP4 level was positively correlated with age, body mass index (BMI), blood pressure, triglycerides, HOMA-R, left ventricular (LV) wall thickness (LVWT; r = 0.39, p &lt; 0.01), and E/e’ (r = 0.32, p &lt; 0.01), an index of impaired LV relaxation, and negatively correlated with the ratio of early diastolic to atrial systolic velocity (E/A) of transmitral flow (r = -0.30, p &lt; 0.01). FABP4 concentration was not significantly correlated with LV ejection fraction or LV diastole diameter. Multiple regression analysis adjusted by age and blood pressure revealed that FABP4 concentration was independently correlated with LVWT and E/e’. However, FABP4 level was not selected as an independent determinant of LVWT or E/e’ when BMI and/or HOMA-R were additionally incorporated into the adjustment. In conclusion, FABP4 may contribute to LV hypertrophy and diastolic dysfunction via facilitation of obesity and insulin resistance in the general population.

Serum Liver Fatty Acid Binding Protein Levels Correlate Positively with Obesity and Insulin Resistance in Chinese Young Adults

BackgroundLiver fatty acid–binding protein (FABP1) plays an inconclusive role in adiposity. We investigated the association of serum FABP1 levels with obesity and insulin resistance in Chinese young people under 30 years old.Methodology and Principal FindingsCross-sectional analysis including 200 obese and 172 normal-weight subjects matched for age and sex, anthropometric measurements were performed and serum FABP1 and biochemical characteristics were measured. Insulin resistance was determined by homeostasis model assessment of insulin resistance (HOMA-IR) and by the insulin sensitivity index (Si) derived from Bergman’s minimal model. FABP1 levels in obese subjects were significantly higher than those in normal-weight subjects (p<0.001) and the significance remained after adjustment for age, gender, alanine and aspartate aminotransferases (p<0.001). Serum FABP1 levels were significantly correlated with many metabolic-related parameters, with BMI and triglycerides as the independent determinants. FABP1 levels remained an independent risk factor of insulin resistance assessed by binary Si (OR = 1.868 per SD unit, 95% CI [1.035–3.373], p = 0.038) after adjustment for age, sex, BMI, waist circumference, systolic blood pressure, serum triacylglycerol, total cholesterol, HDL- and LDL-cholesterol,. FABP1 levels were also elevated with an increasing number of components of the metabolic syndrome (p for trend <0.001). Multiple regression modeling for the MetS and its components demonstrated that hypertriglyceridemia and low HDL-cholesterol were significantly correlated to serum FABP1 levels.Conclusions and SignificanceSerum FABP1 correlates positively with obesity and insulin resistance in Chinese young adults. Our data supports the fact that FABP1 might be an important mediator participating in fatty acid metabolism and energy balance.

199 SERUM FABP4 (A-FABP/AP2) AND FABP5 (E-FABP/MAL1) AS POSSIBLE BIOMARKERS OF INSULIN RESISTANCE AND CORONARY ATHEROSCLEROSIS

Objectives: Fatty acid-binding protein 4 (FABP4/A-FABP/aP2) and 5 (FABP5/E-FABP/mal1) are expressed in both adipocytes and macrophages and paly important roles of development of insulin resistance and atherosclerosis. Recent studies have shown that elevated serum FABP4 is associated with obesity, insulin resistance, and atherosclerosis. However, little is known about the association of FABP5 concentration with insulin resistance and atherosclerosis. Methods: We determined serum levels of FABP4 and FABP5 and severity of coronary stenosis by the modified Gensini's score in coronary angiography in 34 male patients with stable angina pectoris. Results: Serum FABP5 concentration (1.2 ± 0.1 ng/ml) was about 15-fold lower than FABP4 level (18.1 ± 1.5 ng/ml). Both levels of FABP4 and FABP5 were positively correlated with age (r = 0.35, 0.42, respectively), body mass index (BMI; r = 0.42, 0.37), fasting plasma glucose (r = 0.43, 0.35), insulin (r = 0.50, 0.40) and HOMA-R (r = 0.55, 0.45) and negatively correlated with estimated glomerular filtration rate (eGFR; r = -0.34, -0.42). Multiple regression analysis showed that HOMA-R was an independent determinant of both FABP4 and FABP5 after adjustment of age, BMI, and eGFR. Coronary stenosis score was not correlated with age, blood pressure, HOMA-R or LDL cholesterol. There was a significant correlation of coronary stenosis score with FABP4 level (r = 0.37, p = 0.003) but not with FABP5 level (r = 0.26, p = 0.138). Conclusions: Concentration of FABP4 and FABP5 might be novel biomarkers of insulin resistance. FABP4 level might additionally predict severity of coronary atherosclerosis.

Elevation of Fatty Acid-Binding Protein 4 Is Predisposed by Family History of Hypertension and Contributes to Blood Pressure Elevation

BackgroundFatty acid-binding protein 4 (FABP4/A-FABP/aP2), a lipid chaperone, is expressed in both adipocytes and macrophages. Recent studies have shown secretion of FABP4 from adipocytes and association of elevated serum FABP4 level with obesity, insulin resistance, and atherosclerosis. However, little is known about the role of FABP4 in essential hypertension.MethodsWe first examined serum FABP4 concentrations in 18 normotensives (NT) and 30 nontreated essential hypertensives (EHT). The EHT were divided into 18 insulin-sensitive EHT (EHT-S) and 12 insulin-resistant EHT (EHT-R) based on their insulin-sensitivity index, the M value, determined by the hyperinsulinemic–euglycemic clamp technique. In the second study, we determined FABP4 levels in 30 young NT men with or without a family history of hypertension (FH+ and FH–, respectively; n = 15 each).ResultsSerum FABP4 level was significantly higher in the EHT-R than in the NT, whereas elevation of FABP4 level in the EHT-S was not statistically significant. FABP4 level was positively correlated with age, body mass index (BMI), blood pressure, and triglycerides and negatively correlated with the M value. FABP4 level was an independent predictor of mean arterial pressure after adjustment of age, gender, and adiposity. The FH+ group had a significantly lower level of M value and higher level of FABP4 than did the FH– group, and FABP4 concentration was an independent determinant of the M value.ConclusionsFABP4 contributes to blood pressure elevation and atherogenic metabolic phenotype in hypertensives, and the elevation of FABP4 is predisposed by a family history of hypertension.

Abstract 9677: Fatty Acid-Binding Protein 4 is a Novel Predictor of Cardiovascular Events in End-Stage Renal Disease

[Background] Fatty acid-binding protein 4 (FABP4/A-FABP/aP2), a lipid chaperone, is expressed in both adipocytes and macrophages and plays important roles in the regulation of insulin sensitivity and the development of atherosclerosis. Recently, FABP4 was found to be secreted from adipocytes. However, little is known about the impact of serum FABP4 concentrations on development of cardiovascular diseases. Here we tested the hypothesis that serum FABP level predicts prognosis of patients with end-stage renal disease (ESRD), a group at high risk for atherosclerosis-associated morbidity and mortality. [Methods &amp; Results] Biochemical markers including FABP4 were determined in 61 ESRD patients on chronic hemodialysis (HD) and 61 age-, gender- and body mass index (BMI)-matched controls. Serum FABP4 level in females (404.2 ± 30.5 ng/ml) was significantly higher than that in males (315.8 ± 30.0 ng/ml), and the levels in ESRD patients were approximately 20-times higher than those in controls. FABP4 level was decreased by 57.2% after HD and was positively correlated with blood pressure, BMI, and levels of lipids and insulin. Multiple regression analysis indicated that HD duration, BMI, and triglycerides level were independent determinants of serum FABP4 level. Kaplan-Meier survival curves showed that ESRD patients with higher FABP4 levels had higher cardiovascular mortality during the 7-year follow-up period. Cox proportional hazard regression analysis revealed that logarithmically transformed FABP4 level was an independent predictor of cardiovascular death adjusted for age, gender, and HD duration (hazard ratio, 4.89; 95% CI, 1.33-20.23). [Conclusions] Present findings suggest that FABP4 level, being related to adiposity and metabolic disorders, is a novel predictor of cardiovascular mortality in ESRD.

Serum Fatty Acid-Binding Protein 4 Is a Predictor of Cardiovascular Events in End-Stage Renal Disease

BackgroundFatty acid-binding protein 4 (FABP4/A-FABP/aP2), a lipid chaperone, is expressed in both adipocytes and macrophages. Recent studies have shown that FABP4 is secreted from adipocytes and that FABP4 level is associated with obesity, insulin resistance, and atherosclerosis. However, little is known about the impact of FABP4 concentrations on prognosis. We tested the hypothesis that FABP4 level predicts prognosis of patients with end-stage renal disease (ESRD), a group at high risk for atherosclerosis-associated morbidity and mortality.Methods and ResultsBiochemical markers including FABP4 were determined in 61 ESRD patients on chronic hemodialysis (HD). Serum FABP4 level in females (404.2±30.5 ng/ml) was significantly higher than that in males (315.8±30.0 ng/ml), and the levels in ESRD patients were about 20-times higher than those in age-, gender- and body mass index (BMI)-matched control subjects with normal renal function. FABP4 level was decreased by 57.2% after HD and was positively correlated with blood pressure, BMI, and levels of lipids and insulin. Multiple regression analysis indicated that HD duration, BMI, and triglycerides level were independent determinants for FABP4 level. ESRD patients with high FABP4 levels had higher cardiovascular mortality during the 7-year follow-up period. Cox proportional hazard regression analysis showed that logarithmically transformed FABP4 level was an independent predictor of cardiovascular death adjusted for age, gender, HD duration, BMI, and triglycerides level (hazard ratio, 7.75; 95% CI, 1.05–25.31).ConclusionThese findings suggest that FABP4 level, being related to adiposity and metabolic disorders, is a novel predictor of cardiovascular mortality in ESRD.

Expression and regulation of adipocyte fatty acid binding protein in granulosa cells and its relation with clinical characteristics of polycystic ovary syndrome

Increased expression of adipocyte fatty acid binding protein (FABP4) is associated with type 2 diabetic, high triglycerides, increased lipid peroxidation, and inflammation markers. To study the expression of FABP4 mRNA in granulosa cells of patients with polycystic ovary syndrome (PCOS) and the impact of testosterone, insulin, and PPARγ agonist rosiglitazone on granulosa cells (GCs), and to investigate the relationship of serum FABP4 levels with clinical characteristics in patients with PCOS. The expression of FABP4 mRNA in GCs of patients with PCOS and normal controls were assayed by RT-PCR. We assessed the level of FABP4 mRNA after treatment with testosterone, insulin, and rosiglitazone in GCs from normal controls. Serum FABP4 were assayed from 96 patients with PCOS (obese and nonobese 48 cases, respectively) and 80 healthy normal controls (obese and the nonobese 40 cases, respectively). The expression of FABP4 mRNA was higher in the GCs of PCOS than that of the controls (P<0.05). FABP4 mRNA expression was up-regulated by testosterone, insulin, and rosiglitazone at different dosages. Serum FABP4 levels were higher in the nonobese PCOS group than that of the nonobese controls (8.9±5.1 ng/ml vs. 4.8±0.7 ng/ml), and in the obese PCOS group than that of the obese controls (28.2±14.0 ng/ml vs. 15.6±6.6 ng/ml), respectively (P<0.05). Multiple linear regression analyses showed that serum FABP4 level was independently associated with HOMA-IR, BMI, and testosterone (P<0.05). Increased FABP4 was related to the clinical characteristics of PCOS.

The role of serum adipocyte fatty acid-binding protein on the development of metabolic syndrome is independent of pro-inflammatory cytokines

Background and aimAdipocyte fatty acid-binding protein (FABP4) is abundantly expressed in adipocytes and plays a role in glucose homeostasis. We analysed the relationship between serum FABP4 levels and the progression of metabolic syndrome in healthy adults. Methodsand resultsA total of 465 subjects were selected from participants in a medical check-up programme at a Health Promotion Center. Baseline serum FABP4 levels were measured, and the subjects were evaluated for the presence of metabolic syndrome (MetS) according to the recommendations of the American Heart Association/National Heart, Lung, and Blood Institute. The subjects were re-evaluated 4 years later.Baseline FABP4 concentrations were significantly higher in subjects with MetS than in those without MetS (P<0.001). At the 4-year follow-up, subjects in the highest FABP4 tertile at baseline exhibited higher values for body mass index, fat mass and percent body fat, as well as blood pressure, fasting glucose, total cholesterol, triglycerides, low-density lipoprotein (LDL)-cholesterol, insulin, homeostasis model assessment of insulin resistance, monocyte chemoattractant protein-1 and tumor necrosis factor-α levels (all P<0.05). The subjects with higher FABP4 levels had lower HDL-cholesterol concentrations (P<0.05). After adjustment for age, sex, change in percent body fat and baseline values for other metabolic and inflammatory parameters, FABP4 levels at baseline were shown to be strongly associated with the development of MetS by year 4 (odds ratio (OR), 5.75; 95% confidence interval (CI), 2.71–12.23 for highest tertile vs. lowest tertile, P<0.001) ConclusionBaseline serum FABP4 levels appear to be a significant predictor for the future development of MetS, independent of pro-inflammatory cytokines.

Expression and significance of adipocyte fatty acid-binding protein in placenta, serum and umbilical cord blood in preeclampsia

To investigate the change of adipocyte fatty acid-binding protein (FABP4) in maternal serum and umbilical cord blood and FABP4 mRNA placental expression in patients with preeclampsia (PE). A total of 60 women with PE and 60 normal pregnant women as control participated in this study.All are admitted to Fujian Maternity and Children Health Hospital for delivery from December 2008 to October 2009. Patients with PE were divided into early-onset group (n = 30, presented at ≤ 34 weeks of gestation) and late-onset group (n = 30, presented at > 34 weeks of gestation), with 30 normal pregnant women as early control group (≤ 34 weeks of gestation) and 30 as late control group (> 34 weeks of gestation). Enzyme-linked immunosorbent assay (ELISA) was used to detect FABP4, fasting serum glucose, fasting insulin (FINS) in maternal serum and FABP4 in umbilical cord blood. Real-time fluorescent quantitative reverse transcription PCR was used to detect placental FABP4 mRNA expression. Furthermore, clinical and biochemical parameters were recorded, such as body mass index (BMI), systolic pressure (SP), diastolic pressure (DP), mean arterial pressure (MAP), total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), creatinine (Cr), uric acid (UA), glomerular filtration rate (GFR), 24 hours urine protein in pregnant women and neonatal weight. (1) Maternal serum FABP4 was (176 ± 9) ng/L in early-onset PE group and (170 ± 9) ng/L in late-onset PE group, significantly elevated as compared to (81 ± 13) ng/L in early control group and (94 ± 15) ng/L in late control group. (2) Mean maternal FINS, homeostasis model of assessment for insulin resistence index (HOMA-IR) were significantly elevated in the early-onset PE group and late-onset PE group as compared to control groups, respectively. (3) Mean placental FABP4 mRNA expression were significantly elevated in the early-onset PE group and late-onset PE group as compared to late control group. However, no significant difference was found in placental FABP4 mRNA expression between early-onset and late-onset PE groups. (4) Mean umbilical cord blood FABP4 concentrations were significantly decreased in the early-onset PE group and late-onset PE group as compared to late control group. Furthermore, umbilical cord blood FABP4 concentration correlated negatively with maternal serum FABP4 level and placental FABP4 mRNA expression, but positively with neonatal weight. (5) Mean maternal serum FABP4 concentrations correlated positively with placental FABP4 mRNA expression, TG, FINS, HOMA-IR, Cr, UA; and negatively with HDL, GFR. Increased FABP4 expression in maternal serum and placenta may be involved in the pathogenesis of preeclampsia. Increased FABP4 mRNA expression in placenta may contribute to high serum FABP4 level in women with PE.

Plasma concentrations of adipocyte fatty acid binding protein in patients with Cushing's syndrome

Serum adipocyte fatty acid-binding protein (FABP-4) concentrations are linked to human obesity and other features of metabolic syndrome. Patients with Cushing´s syndrome (CS) develop numerous features of metabolic syndrome due to chronic cortisol excess. Here we tested the hypothesis that chronically increased cortisol levels in CS patients may alter circulating levels of FABP-4. Fourteen patients with CS, 19 patients with simple obesity (OB) and 36 healthy control subjects (C) were included in the study. Serum FABP-4 concentrations were significantly higher in both CS and OB patients relative to C group, but they did not differ between CS and OB groups. In a combined population of all groups, serum FABP-4 levels correlated positively with BMI, body fat content, serum glucose, triglycerides, HbA1c and HOMA index and were inversely related to HDL-cholesterol, resting energy expenditure and freeT3 levels. We conclude that FABP-4 levels are significantly increased in both patients with simple obesity and obese patients with Cushing´s syndrome. We suggest that increased FABP-4 concentrations in CS patients are rather due to their excessive fat accumulation and related metabolic abnormalities than due to a direct effect of cortisol on FABP-4 production.

FABP4: a novel candidate gene for polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a complex multifactorial disorder involving a number of genetic and environmental factors. Adipocyte-fatty acid-binding protein (FABP4) is an adipokine regulating systemic insulin sensitivity, lipid and glucose metabolism. In humans serum FABP4 levels correlate significantly with features of PCOS. Previous researches showed strong evidences that FABP4 impacted the developing of PCOS possibly through its protein alteration or transcription regulation. Thus, the present study is the first attempt to identify the possible genetic role of FABP4 gene in the development of PCOS. About 1000 bp of the promoter region and four exons of FABP4 gene of 178 PCOS patients and 171 healthy controls were directly sequenced. Three polymorphisms, rs16909225, rs3834363, and rs16909220, were identified, of which rs16909225 and rs16909220 were completely linked (r² = 1) and not associated with the development of PCOS, while the -2-bp/-2-bp genotype of rs3834363 was significantly higher in PCOS than in the controls (χ² = 7.39, df = 1, P = 0.007, OR = 1.80 95% CI: 1.18-2.75). The present study is the first to establish an association between FABP4 gene polymorphisms and the development of PCOS.

Serum fatty acid binding protein 4, free fatty acids, and metabolic risk markers

Fatty acid binding protein (FABP) 4 chaperones free fatty acids (FFAs) in the adipocytes during lipolysis. Serum FFA relates to metabolic syndrome, and serum FABP4 is emerging as a novel risk marker. In 36 overweight/obese women, serum FABP4 and FFA were measured hourly during 5-hour oral glucose tolerance test. Insulin resistance was determined using frequently sampled intravenous glucose tolerance test. Serum lipids and inflammation markers were measured at fasting. During oral glucose tolerance test, serum FABP4 decreased by 40%, reaching its nadir at 3 hours (from 45.3 ± 3.1 to 31.9 ± 1.6 ng/mL), and stayed below the baseline at 5 hours (35.9 ± 2.2 ng/mL) ( P < .0001 for both, compared with the baseline). Serum FFA decreased by 10-fold, reaching a nadir at 2 hours (from 0.611 ± 0.033 to 0.067 ± 0.004 mmol/L), then rebounded to 0.816 ± 0.035 mmol/L at 5 hours ( P < .001 for both, compared with baseline). Both fasting FABP4 and nadir FABP4 correlated with obesity. Nadir FABP4 correlated also with insulin resistance parameters from frequently sampled intravenous glucose tolerance test and with inflammation. Nadir FFA, but not fasting FFA, correlated with the metabolic syndrome parameters. In conclusion, fasting FABP4 related to metabolic risk markers more strongly than fasting FFA. Nadir FABP4 and nadir FFA measured after glucose loading may provide better risk assessment than the fasting values.

The association of serum adipocyte fatty acid-binding protein with coronary artery disease in Korean adults

Adipocyte fatty acid-binding protein (A-FABP), also known as aP2 or FABP4, is abundantly expressed in adipocytes and plays a role in glucose homeostasis. We analyzed the relationship between the coronary artery disease and serum FABP4 levels in Korean adults. In a total of 234 Korean adults, in whom coronary angiograms were performed, anthropometric measurements were done and fasting glucose and lipid profiles were measured. Serum FABP4 levels were measured using ELISA. The presence of metabolic syndrome was diagnosed according to American Heart Association/National Heart, Lung and Blood Institute (AHA/NHBL) criteria with body mass index (BMI) substituted for waist circumference. Among the subjects, 31.6% had diabetes, 46.9% had metabolic syndrome, and mean log (FABP4) levels showed significantly higher levels in subjects with diabetes. Among the subjects, 42.4% had normal coronary vessel, 34.6% had 1-vessel disease, 13.7% had 2-vessel disease, and 9.4% had 3-vessel disease. Among the parameters, mean age, fasting glucose, and log (FABP4) levels increased significantly as the numbers of stenotic vessel increased from normal to 3-vessel disease, and for FABP4, these significances showed a consistent trend for difference after adjustment for age, gender, BMI, and fasting glucose (P=0.072). Mean log (FABP4) level showed lower values in subjects taking aspirin, and higher values in subjects taking statin and anti-hypertensive drugs. Serum FABP4 levels increased as the numbers of stenotic coronary artery increased, although these differences were attenuated after adjustment for age and fasting glucose levels. Various anti-atherogenic medications showed different effects on the serum FABP4 levels, which need further investigation.