Adipocyte Fatty Acid-binding Protein Levels Research Articles

Development of a therapeutic monoclonal antibody against circulating adipocyte fatty acid binding protein to treat ischaemic stroke.

Adipocyte fatty acid-binding protein (A-FABP) exacerbates cerebral ischaemia injury by disrupting the blood-brain barrier (BBB) through inducing expression of MMP-9. Circulating A-FABP levels positively correlate with infarct size in stroke patients. We hypothesized that targeting circulating A-FABP by a neutralizing antibody would alleviate ischaemic stroke outcome. Monoclonal antibodies (mAbs) against A-FABP were generated using mouse hybridoma techniques. Binding affinities of a generated mAb named 6H2 towards various FABPs were determined using Biacore. Molecular docking studies were performed to characterize the 6H2-A-FABP complex structure and epitope. The therapeutic potential and safety of 6H2 were evaluated in mice with transient middle cerebral artery occlusion (MCAO) and healthy mice, respectively. Replenishment of recombinant A-FABP exaggerated the stroke outcome in A-FABP-deficient mice. 6H2 exhibited nanomolar to picomolar affinities to human and mouse A-FABP, respectively, with minimal cross-reactivities with heart and epidermal FABPs. 6H2 effectively neutralized JNK/c-Jun activation elicited by A-FABP and reduced MMP-9 production in macrophages. Molecular docking suggested that 6H2 interacts with the "lid" of the fatty acid binding pocket of A-FABP, thus likely hindering the binding of its substrates. In mice with transient MCAO, 6H2 significantly attenuated BBB disruption, cerebral oedema, infarction, neurological deficits, and decreased mortality associated with reduced cytokine and MMP-9 production. Chronic 6H2 treatment showed no obvious adverse effects in healthy mice. These results establish circulating A-FABP as a viable therapeutic target for ischaemic stroke, and provide a highly promising antibody drug candidate with high affinity and specificity.

Dysregulation of adipokines levels among healthy first-degree relatives of type 2 diabetes patients

BackgroundLeptin, adiponectin and its ratio (L/A), as well as adipocyte fatty acid binding protein (A-FABP) have shown association to type 2 diabetes and atherosclerosis. Since first degree relatives (FDR) of type 2 diabetes are known to have higher risks of developing aforementioned diseases, this study aimed to see differences in adipokines profiles between FDR of type 2 diabetes and non-FDR counterpart. MethodsAge, sex and body mass index (BMI)-matched normotensive-normoglycemic subjects, aged 19–39 years with BMI<30 kg/m2, were included in this cross-sectional study. Serum adiponectin, leptin, and A-FABP levels were measured by sandwich ELISA while HOMA-IR was calculated from fasting blood glucose and insulin levels. ResultsOf 116 subjects recruited, there were significant difference of insulin level (6.00 vs 5.00 μIU/mL, P = 0.029) and HOMA-IR (1.27 vs 1.10, P = 0.028). Adiponectin, leptin, L/A ratio, and A-FABP levels were not statistically different between FDR and non-FDR groups. Stratified by BMI, non-obese FDR had higher L/A ratio (0.83 vs 0.49, P = 0.020) compared to those of corresponding non-FDR. In multivariate analysis, after adjusting for age, sex, waist circumference, BMI, and metabolic profiles (HbA1C, HOMA-IR, LDL-C, HDL-C, and triglyceride levels), FDR status became significantly associated with adiponectin level, and in non-obese subgroup, remained its significance with L/A ratio. ConclusionThe FDR status was independently associated with adiponectin level. Furthermore, higher L/A ratio was more pronounced in non-obese FDR than those of non-FDR subjects, suggesting that FDR status may already contribute to the development of adipokines dysregulation before obesity occurs.

Study on the Association Between Dietary Quality and Overweight/Obesity of Han Nationality with Cold in Yunnan Plateau by DBI-16 - A Study Based on a Multi-Ethnic Cohort in China.

In recent years, with the rapidly development of economic globalization, residents' dietary structure has undergone major changes, and diet have emerged as an important environmental factors linked to the increased incidence of obesity. Therefore, evaluating the overall dietary quality and structure of residents, further clarifying the main dietary factors that lead to disease occurrence, is of great practical significance for disease prevention and control. Baseline data from the China Multi-Ethnic Cohort study (CMEC), Han people living in high-altitude and cold regions of Yunnan Province, which was 1518 participants. In this study, the dietary balance index (DBI-16) was used (i) To evaluate the dietary quality of Han nationality residents 30-79 years old in the Yunnan plateau; (ii) To analyze the correlation between the dietary quality and overweight/obesity; (iii) And to provide reference basis of nutritional intervention for local residents and explore the main dietary factors affecting their health status. The dietary structure of the Han nationality residents in the cold regions of Yunnan plateau is unreasonable. Firstly, the intake of cereals, fruits, dairy, eggs and fishes is insufficient to varying degrees, while the intake of beans, poultry, and cooking oil is relatively high. Secondly, the dietary patterns of normal groups, the overweight and obese groups obeyed the A, E, H and I dietary patterns, and the serum Leptin and adipocyte fatty acid binding protein (A-FABP) levels of the overweight and obese group were higher than the normal group between the different dietary patterns (P < 0.05, r > 0). Additionally, excessive dietary intake was positively correlated with a higher serum UCP1 level (P < 0.05, r > 0). In comparison, insufficient dietary intake was positively correlated with a higher serum A-FABP level (P < 0.05, r > 0). Through the DBI-16, it is found that the dietary structure of the Han nationality residents in the cold regions of Yunnan plateau was in a serious imbalance state, and nutritional guidance and intervention should be further strengthened.

Elevated Serum Concentration of Adipocyte Fatty Acid-Binding Protein Correlates with the Markers of Abdominal Obesity Independently of Thyroid Hormones in Non-Obese Women with Polycystic Ovary Syndrome.

Adipocyte fatty acid-binding protein (A-FABP) is mainly expressed in adipocytes. The risk of abdominal obesity and autoimmune thyroid disease is increased in women with polycystic ovary syndrome (PCOS). The objective of this study was to explore the relationship of serum concentration of A-FABP with parameters of obesity, e.g., waist to hip ratio (WHR) and the amount of adipose tissue assessed by bioelectrical impedance analysis (BIA), and thyroid hormone homeostasis in women with PCOS. We examined 66 women with PCOS and 67 healthy women. Serum concentrations of A-FABP and thyroid hormones were measured; the FT3/FT4 ratio, thyroid-stimulating hormone index (TSHI), thyrotrope thyroxine resistance index (TT4RI) and thyroid feedback quantile-based index (TFQI) were calculated. In the PCOS group, serum concentrations of A-FABP, FT3 and the FT3/FT4 ratio were significantly higher in comparison to the control group (all p < 0.05). A correlation of A-FABP with WHR (r = 0.26, p = 0.04) and the percentage of adipose tissue (r = 0.33, p = 0.01) has been found only in women with PCOS. We observed no correlation between serum levels of A-FABP and TSHI, TT4RI or TFQI in women with PCOS (all p > 0.05). Our results indicate that A-FABP is an adipokine that may be connected with abdominal obesity independently of thyroid hormone homeostasis in PCOS patients.

The Interplay of Adipokines, Body Composition and Glucose Homeostasis in Pregnant Women with a History of RYGB Operation.

Roux-en-Y gastric bypass operations (RYGB-OP) and pregnancy alter glucose homeostasis and the adipokine profile. This study investigates the relationship between adipokines and glucose metabolism during pregnancy post-RYGB-OP. (1) Methods: This is a post hoc analysis of a prospective cohort study during pregnancy in 25 women with an RYGB-OP (RY), 19 women with obesity (OB), and 19 normal-weight (NW) controls. Bioimpedance analysis (BIA) was used for metabolic characterization. Plasma levels of adiponectin, leptin, fibroblast-growth-factor 21 (FGF21), adipocyte fatty acid binding protein (AFABP), afamin, and secretagogin were obtained. (2) Results: The phase angle (φ) was lower in RY compared to OB and NW. Compared to OB, RY, and NW had lower leptin and AFABP levels, and higher adiponectin levels. φ correlated positively with leptin in RY (R = 0.63, p < 0.05) and negatively with adiponectin in OB and NW (R = -0.69, R = -0.69, p < 0.05). In RY, the Matsuda index correlated positively with FGF21 (R = 0.55, p < 0.05) and negatively with leptin (R = -0.5, p < 0.05). In OB, FGF21 correlated negatively with the disposition index (R = -0.66, p < 0.05). (3) Conclusions: The leptin, adiponectin, and AFABP levels differ between RY, OB, and NW and correlate with glucose metabolism and body composition. Thus, adipokines might influence energy homeostasis and maintenance of cellular health during pregnancy.

Circulating AFABP, FGF21, and PEDF Levels as Prognostic Biomarkers of Sight-threatening Diabetic Retinopathy.

Adipocyte fatty acid-binding protein (AFABP), fibroblast growth factor 21 (FGF21), and pigment epithelium-derived factor (PEDF) are 3 diabetes-related biomarkers whose circulating levels had been shown to associate with nephropathy progression in Chinese patients with type 2 diabetes. Here, we evaluated and compared their prospective associations with the development of sight-threatening DR (STDR), another important diabetic microvascular complication. Baseline serum AFABP, PEDF, and FGF21 levels were measured in 4760 Chinese individuals with type 2 diabetes and without STDR at baseline. The associations of these biomarkers with incident STDR were analyzed using Cox regression analysis. Among these 4760 participants (mean diabetes duration of 11 years and ≥ 50% with nonproliferative DR at baseline), 172 participants developed STDR over a median follow-up of 8.8 years. Participants with incident STDR had comparable baseline serum FGF21 levels but significantly higher baseline serum AFABP and PEDF levels (both P < .001) than those without. However, in multivariable Cox regression analysis, only serum AFABP remained independently associated with incident STDR (hazard ratio 1.28; 95% CI, 1.05-1.55; P = .013). The addition of serum AFABP to a clinical model of conventional STDR risk factors including diabetes duration, glycemic control, albuminuria, and baseline DR status significantly improved the c statistics (P < .001), net reclassification index (P = .0027), and integrated discrimination index (P = .033) in predicting incident STDR among participants without DR or with mild DR at baseline. Among the 3 diabetes-related biomarkers, serum AFABP level appeared to be a more clinically useful biomarker for predicting incident STDR in type 2 diabetes.

The Association and Joint Effect of Adipocyte Fatty Acid Binding Protein and Obesity Phenotype With Cardiovascular Events.

There is little evidence regarding the joint effect of serum adipocyte fatty acid binding protein (A-FABP) levels and obesity phenotype on the risk of cardiovascular events. To explore the association between serum A-FABP levels and obesity phenotype defined by fat percentage (fat%) and visceral fat area (VFA), and their joint impact on incident cardiovascular events. A total of 1345 residents (579 men and 766 women) without previous cardiovascular diseases at baseline, with body composition and serum A-FABP data available, were included. A bioelectrical impedance analyzer and magnetic resonance imaging were used to assess fat% and VFA, respectively. During a mean follow-up of 7.6 years, 136 cases of cardiovascular events (13.9 per 1000 person-years) occurred. Per 1-unit increase in loge-transformed A-FABP levels was associated with an increase in cardiovascular events risk (hazard ratio [HR] 1.87, 95% CI 1.33-2.63). The highest tertiles of fat% and VFA levels were related to higher risks of cardiovascular events (fat%: HR 2.38, 95% CI 1.49-3.81; VFA: HR 1.79, 95% CI 1.09-2.93). The association between A-FABP levels and cardiovascular events was more pronounced in participants with low fat%, regardless of VFA levels. The joint effect of high A-FABP levels and obesity resulted in a greater risk of cardiovascular events. Serum A-FABP levels were significantly associated with the risk of cardiovascular events, and this pattern of association was more prominent among the population with low fat%, which was independent of VFA.

Serum Adipocyte Fatty-Acid Binding Protein as an Independent Marker of Peripheral Artery Disease in Patients with Type-2 Diabetes Mellitus.

The adipocyte fatty-acid binding protein (A-FABP) is predominantly expressed in macrophages and adipocytes and is an essential mediator of inflammation and atherosclerosis pathogenesis. Atherosclerosis is an aggravating factor for peripheral arterial disease (PAD). Our study intended to study the association between PAD and serum A-FABP levels in type-2 diabetes mellitus (T2DM) patients. One hundred and twenty T2DM subjects were enrolled in the study. Fasting blood samples were collected to determine biochemical data and A-FABP levels. By the automatic oscillometric method, the ankle–brachial index (ABI) was measured. Low ABI was defined as any value < 0.9. Twenty participants with T2DM (16.7%) were included in the low ABI group. Low ABI T2DM participants had an increased mean body mass index, body fat mass, systolic blood pressure, C-reactive protein, urine albumin–creatinine ratio, and A-FABP levels compared to those in the normal ABI group. After variables significantly associated with PAD were adjusted by multivariate logistic regression analyses, circulating A-FABP levels (odds ratio [OR]: 1.138; 95 percent confidence interval [CI]: 1.023–1.266; p = 0.017) were identified as the independent marker of PAD. In conclusion, fasting serum A-FABP value has positive association with PAD in T2DM patients.

Serum adipocyte fatty acid-binding protein level is positively associated with aortic stiffness in nondialysis chronic kidney disease patients: A cross-sectional study.

Aortic stiffness (AS) is a major predictor of cardiovascular disease and mortality in patients with chronic kidney disease (CKD) and adipocyte fatty acid-binding protein (A-FABP) is a novel adipokine that is positively correlated with AS in the general population. Therefore, we investigated the correlation between serum A-FABP levels and AS in nondialysis CKD patients.Fasting blood samples and baseline characteristics were obtained in 270 patients with nondialysis CKD. Serum A-FABP concentrations were determined by enzyme immunoassay and carotid–femoral pulse wave velocity (cfPWV) measurements were acquired using a validated tonometry system. Patients with cfPWV >10 m/s formed the AS group, while those with values ≤10 m/s comprised the comparison group.Among 270 CKD patients, 92 patients (34.1%) were in the AS group. Compared to those in the comparison group, patients in the AS group were older (P < .001), had a higher prevalence of diabetes, along with higher serum A-FABP level (P < .001), larger waist circumference (P = .004), and lower estimated glomerular filtration rate (P = .001) but higher levels of body fat mass (P = .010), systolic blood pressure (P < .001), fasting glucose (P = .014), blood urea nitrogen (P = .009), and serum creatinine (P = .004). The serum log-A-FABP level was positively associated with log-cfPWV (β = 0.178, P = .001) in nondialysis CKD patients and multivariable logistic regression analysis identified serum A-FABP (P = .006), age (P = .001), and systolic blood pressure (P = .015) as independent predictors of AS in nondialysis-dependent CKD patients.Elevated A-FABP levels may be a significant predictor of AS in nondialysis CKD patients.

Adiponectin, A-FABP and FGF-19 Levels in Women with Early Diagnosed Gestational Diabetes.

Background: Adiponectin, adipocyte fatty acid-binding protein (A-FABP), and fibroblast growth factor-19 (FGF-19) belong to proteins involved in glucose metabolism regulation. The aims of the study were to compare the plasma levels of these proteins in women with early diagnosed gestational diabetes mellitus (GDM) to those in healthy controls and to investigate their changes during pregnancy after early intervention. Methods: The study was undertaken as a case-control study. Early GDM diagnosis was based on repeated fasting plasma glucose ≥5.1 and <7.0 mmol/L during the first trimester of pregnancy and exclusion of overt diabetes. Age-matched controls comprised healthy pregnant and non-pregnant women. In addition to adipokines, clinical parameters and measures of glucose control were assessed. Results: Women with GDM (n = 23) had significantly lower adiponectin and higher A-FABP levels compared to healthy pregnant (n = 29) or non-pregnant (n = 25) controls, while no significant differences in FGF-19 between the groups were found. The therapeutic intervention shifted adiponectin and A-FABP levels in GDM women towards concentrations of healthy pregnant controls. Adipokines were associated with visceral adiposity and glucose control. Conclusion: Women with GDM showed altered adipokine production even in the first trimester of pregnancy. Early therapeutic intervention not only improved glucose control but also normalized impaired adipokine production.

Age and Serum Adipocyte Fatty-Acid-Binding Protein Level Are Associated with Aortic Stiffness in Coronary Artery Bypass Graft Patients.

Old age has been proven to be related to progressed arterial or aortic stiffness. Aortic stiffness is an independent predictor of all-cause and cardiovascular disease mortalities in patients who have undergone coronary artery bypass grafting (CABG) surgery. Higher serum concentrations of adipocyte fatty-acid-binding protein (A-FABP) could be considered a predictor of aortic stiffness in patients with hypertension or diabetes mellitus. This study aims to investigate the relationships between A-FABP and aortic stiffness in patients who have received CABG. A total of 84 CABG patients were enrolled in our study from September 2018 to May 2019. Serum A-FABP levels were determined using a commercial enzyme immunoassay. Carotid–femoral pulse wave velocity (cfPWV) > 10 m/s was defined as aortic stiffness. Of the 84 CABG patients, 28 (33.3%) with aortic stiffness had a higher average age; exhibited higher rates of diabetes; and had higher serum creatinine, C-reactive protein, and A-FABP levels compared to controls. Multivariable logistic regression revealed that serum A-FABP levels (odds ratio (OR) = 1.068, 95% confidence interval (CI) 1.017–1.121, p = 0.008) and age (OR = 1.204, 95% CI 1.067–1.359, p = 0.003) were independent predictors of aortic stiffness. Multivariable stepwise linear regression revealed significant positive correlations of age and A-FABP levels with cfPWV values. Serum A-FABP level is positively correlated with cfPWV values, and a high serum A-FABP level is associated with aortic stiffness in patients who have undergone CABG.

Association between Serum Adipocyte Fatty Acid Binding Protein Level and Endothelial Dysfunction in Chronic Hemodialysis Patients.

Adipocyte fatty acid binding protein (A-FABP) is associated with atherosclerosis, and endothelial dysfunction is one of the reasons for adverse cardiovascular outcomes in patients undergoing hemodialysis (HD). This study investigated the correlation between serum A-FABP levels and endothelial function in HD patients. Fasting blood samples were collected from 90 HD patients. A-FABP levels were measured using a commercial enzyme immunoassay kit. Endothelial function was evaluated by a digital thermal monitoring test to measure vascular reactivity index (VRI). VRI < 1.0, 1.0 ≤ VRI < 2.0, and VRI ≥ 2.0 indicated poor, intermediate, and good vascular reactivity, respectively. In total, 14 (15.6%), 38 (42.2%), and 38 (42.2%) HD patients had poor, intermediate, and good VRI, respectively. Patients with poor VRI had lower pre-HD and post-HD body weight, body mass index, and serum creatinine level but higher serum A-FABP level (p = 0.001) than those with intermediate and good VRI. Log-transformed VRI (log-VRI) positively correlated with serum creatinine and negatively correlated with A-FABP by multivariate linear regression analysis. We concluded that A-FABP correlated with endothelial dysfunction in chronic HD patients.

Torreya nucifera seed oil improves 3T3-L1 adipocyte differentiation

BackgroundAdipose tissue is a critical regulator of lipid storage and endocrine function. Impairment of the recruitment of new adipocytes in the adipose tissue is associated with ectopic fat accumulation, diabetes and insulin resistance. Torreya nucifera, an evergreen conifer that grows in warm temperate climates, has been found to exert beneficial effects against inflammation, infection and diabetes. However, the molecular mechanisms responsible for these effects at the cellular level remain unknown. This study aimed to investigate effects of Torreya nucifera seed oil (TNSO) on 3T3-L1 adipocyte differentiation and its underlying regulatory mechanism.MethodsTo investigate the effects of TNSO on adipocyte differentiation, 3T3-L1 cells were induced to differentiate for 5 days in the presence of 0.75 μL/mL TNSO. Oil Red O staining and an assay for intracellular triglyceride were performed to determine the extent of lipid accumulation in 3T3-L1 cells. To elucidate the underlying mechanism of TNSO, adipogenic gene expression was analyzed using quantitative real-time PCR. Moreover, we monitored TNSO-derived activation of PPARγ and STAT3 with 3T3-L1 reporter cell lines engineered to secrete Gaussia luciferase upon the interaction of a transcription factor to its DNA binding element.ResultsOil Red O staining revealed that TNSO improved the differentiation of 3T3-L1 preadipocytes into mature adipocytes. The mRNA levels of adipogenic genes, including adiponectin, fatty acid synthase (FAS) and adipocyte fatty acid-binding protein (FABP4), were upregulated and intracellular triglyceride levels increased upon TNSO treatment. We also established that adipocyte differentiation was improved by TNSO-derived activation of PPARγ and STAT3.ConclusionsOur results suggest that TNSO improves adipocyte differentiation by regulating the activation of adipogenic transcription factors, indicating that it may serve as a potential treatment strategy for adipocyte dysfunction.

A-FABP in Metabolic Diseases and the Therapeutic Implications: An Update.

Adipocyte fatty acid-binding protein (A-FABP), which is also known as ap2 or FABP4, is a fatty acid chaperone that has been further defined as a fat-derived hormone. It regulates lipid homeostasis and is a key mediator of inflammation. Circulating levels of A-FABP are closely associated with metabolic syndrome and cardiometabolic diseases with imminent diagnostic and prognostic significance. Numerous animal studies have elucidated the potential underlying mechanisms involving A-FABP in these diseases. Recent studies demonstrated its physiological role in the regulation of adaptive thermogenesis and its pathological roles in ischemic stroke and liver fibrosis. Due to its implication in various diseases, A-FABP has become a promising target for the development of small molecule inhibitors and neutralizing antibodies for disease treatment. This review summarizes the clinical and animal findings of A-FABP in the pathogenesis of cardio-metabolic diseases in recent years. The underlying mechanism and its therapeutic implications are also highlighted.

Prospective association of serum adipocyte fatty acid-binding protein with heart failure hospitalization in diabetes.

AimsAdipocyte fatty acid‐binding protein (AFABP) is associated with cardiovascular diseases in type 2 diabetes. Whether circulating AFABP levels are associated with the risk of heart failure (HF) in type 2 diabetes remains undefined. We investigated the prospective association of circulating AFABP levels with incident HF hospitalization in type 2 diabetes, and its relationship to the use of sodium glucose co‐transporter 2 inhibitors (SGLT2i) which reduce HF risk.Methods and resultsBaseline serum AFABP level was measured in 3322 Chinese participants without known history of cardiovascular diseases or hospitalization for HF, recruited from the Hong Kong West Diabetes Registry. Its association with incident HF hospitalization was evaluated using multivariable Cox regression analysis. Use of SGLT2i was included as a time‐dependent covariate. Among these 3322 participants (52.9% men; mean age 60.0 ± 12.6), 176 (5.3%) developed HF hospitalization over a median follow‐up of 8 years. Seven hundred and thirty‐one (22%) were started on SGLT2i during the study period (empagliflozin 55.1%, dapagliflozin 44.2%, canagliflozin 0.4%, and ertugliflozin 0.3%). Serum AFABP levels were significantly higher in participants who developed HF hospitalization than those who did not (men: 14.8 vs. 8.3 ng/mL; women: 21.5 vs. 14.6 ng/mL; all: 18.6 vs. 10.9 ng/mL, P < 0.001). In multivariable Cox regression analysis, baseline serum AFABP level was significantly associated with incident HF hospitalization [hazard ratio (HR) 1.38, 95% confidence interval (CI) 1.06–1.80, P = 0.019] independent of the use of SGLT2i, in a model also consisting of age; sex; body mass index; smoking status; duration of diabetes; hypertension, dyslipidaemia; atrial fibrillation; presence of chronic kidney disease and albuminuria; glycated haemoglobin and high‐sensitivity C‐reactive protein levels; and use of metformin, insulin, aspirin, furosemide, and beta‐blockers at baseline. High cumulative defined daily dose (cDDD) of SGLT2i was protective of incident HF hospitalization (HR 0.10, 95% CI 0.01–0.68, P = 0.019). The addition of circulating AFABP level to a clinical model of conventional HF risk factors provided significant improvement in the category‐free net reclassification index (11.5%, 95% CI 1.6–22.1, P = 0.02) and integrated discrimination improvement (0.3%, 95% CI 0.1–1.7, P = 0.04). A dose‐dependent reduction in cumulative incidence of HF hospitalization in response to SGLT2i, based on cDDD, was more clearly observed in participants with a higher baseline AFABP level above the sex‐specific median (P for trend <0.01).ConclusionsCirculating AFABP level is independently associated with incident HF hospitalization in type 2 diabetes and is potentially helpful in risk stratification for the prevention of HF hospitalization.

Increased Serum Adipocyte Fatty Acid-Binding Protein Concentrations Are Associated with Aortic Stiffness in Nondialysis Diabetic Kidney Disease

BACKGROUND: Adipocyte fatty acid-binding protein (A-FABP) is a novel adipokine with proinflammatory properties that contributes to the development of cardiovascular disease. This cross-sectional study evaluated the correlation between serum A-FABP and aortic stiffness in patients with stages 3-5 nondialysis chronic kidney disease due to type 2 diabetes mellitus (T2DM). METHODS: Fasting blood samples were obtained from 96 patients with stages 3-5 nondialysis chronic kidney disease due to T2DM. Pressure applanation tonometry was used to measure the carotid-femoral pulse wave velocity (cfPWV). Patients with a cfPWV ＞ 10 m/s were defined as having increased aortic stiffness according to the guidelines of the European Society of Hypertension and European Society of Cardiology 2013. Serum A-FABP levels were determined using a commercial enzyme immunoassay. RESULTS: There were 53 (55.2%) patients in the aortic stiffness group, of which higher prevalence rates were found for the male sex (P = 0.015), older age (P = 0.025), higher systolic blood pressure (BP) (P = 0.001), diastolic BP (P = 0.037), urine albumin/creatinine ratio (P = 0.007), serum levels of total cholesterol (P = 0.030), low-density lipoprotein cholesterol (P = 0.043), and A-FABP (P ＜ 0.001) compared with the group with normal aortic stiffness. After adjusting for factors that are significantly associated with aortic stiffness based on multivariable logistic regression analysis, serum A-FABP (odds ratio, 1.487; 95% confidence interval, 1.210-1.829; P ＜ 0.001) was an independent predictor of aortic stiffness in patients with diabetes-associated stages 3-5 nondialysis chronic kidney disease. Multivariable regression analysis with forward stepwise selection revealed that the serum level of logarithmically transformed A-FABP (β = 0.587; adjusted R^2 change, 0.426; P ＜ 0.001) was positively associated with cfPWV in patients with diabetes-associated stages 3-5 nondialysis chronic kidney disease. CONCLUSION: After adjusting for significant confounders, the serum A-FABP level was positively correlated with cfPWV and was an independent predictor of aortic stiffness in patients with diabetes-associated stages 3-5 nondialysis chronic kidney disease.

Adipocyte Fatty Acid-Binding Protein, Cardiovascular Diseases and Mortality.

It has been increasingly recognized that inflammation plays an important role in the pathogenesis of cardiovascular disease (CVD). In obesity, adipose tissue inflammation, especially in the visceral fat depots, contributes to systemic inflammation and promotes the development of atherosclerosis. Adipocyte fatty acid-binding protein (AFABP), a lipid chaperone abundantly secreted from the adipocytes and macrophages, is one of the key players mediating this adipose-vascular cross-talk, in part via its interaction with c-Jun NH2-terminal kinase (JNK) and activator protein-1 (AP-1) to form a positive feedback loop, and perpetuate inflammatory responses. In mice, selective JNK inactivation in the adipose tissue significantly reduced the expression of AFABP in their adipose tissue, as well as circulating AFABP levels. Importantly, fat transplant experiments showed that adipose-specific JNK inactivation in the visceral fat was sufficient to protect mice with apoE deficiency from atherosclerosis, with the beneficial effects attenuated by the continuous infusion of recombinant AFABP, supporting the role of AFABP as the link between visceral fat inflammation and atherosclerosis. In humans, raised circulating AFABP levels are associated with incident metabolic syndrome, type 2 diabetes and CVD, as well as non-alcoholic steatohepatitis, diabetic nephropathy and adverse renal outcomes, all being conditions closely related to inflammation and enhanced CV mortality. Collectively, these clinical data have provided support to AFABP as an important adipokine linking obesity, inflammation and CVD. This review will discuss recent findings on the role of AFABP in CVD and mortality, the possible underlying mechanisms, and pharmacological inhibition of AFABP as a potential strategy to combat CVD.

Epicardial Adiposity in Relation to Metabolic Abnormality, Circulating Adipocyte FABP, and Preserved Ejection Fraction Heart Failure.

Epicardial adipose tissue (EAT) as a source of pro-inflammatory cytokines tightly linked to metabolic abnormalities. Data regarding the associations of EAT with adipocyte fatty acid-binding protein (A-FABP), a cytokine implicated in the cardiometabolic syndrome, might play an important part in mediating the association between EAT and cardiac structure/function in preserved ejection fraction heart failure (HFpEF). We conducted a prospective cohort study comprising 252 prospectively enrolled study participants classified as healthy (n = 40), high-risk (n = 161), or HFpEF (n = 51). EAT was assessed using echocardiography and compared between the three groups and related to A-FABP, cardiac structural/functional assessment utilizing myocardial deformations (strain/strain rates) and HF outcomes. EAT thickness was highest in participants with HFpEF (9.7 ± 1.7 mm) and those at high-risk (8.2 ± 1.5 mm) and lowest in healthy controls (6.4 ± 1.9 mm, p < 0.001). Higher EAT correlated with the presence of cardiometabolic syndrome, diabetes and renal insufficiency independent of BMI and waist circumference (pinteraction for all > 0.1), and was associated with reduced LV global longitudinal strain (GLS) and LV mass-independent systolic/diastolic strain rates (SRs/SRe) (all p < 0.05). Higher A-FABP levels were associated with greater EAT thickness (pinteraction > 0.1). Importantly, in the combined control cohort, A-FABP levels mediated the association between EAT and new onset HF. Excessive EAT is independently associated with the metabolic syndrome, renal insufficiency, and higher A-FABP levels. The association between EAT and new onset HF is mediated by A-FABP, suggesting a metabolic link between EAT and HF.

Positive Associations between Adipocyte Fatty Acid-Binding Protein Level and Central Arterial Stiffness in Peritoneal Dialysis Patients.

Background Adipocyte fatty acid-binding protein (A-FABP) plays essential roles in lipolysis, insulin resistance, and atherosclerosis. This study aimed to evaluate the relationship between serum A-FABP levels and carotid-femoral pulse wave velocity (cfPWV) in peritoneal dialysis (PD) patients. Methods This study obtained fasting blood samples from 76 PD patients. A validated tonometry system was used to measure cfPWV. Patients with cfPWV values >10 m/s were classified into the high arterial stiffness group, whereas patients with values ≤10 m/s were classified into the low arterial stiffness group, according to the ESH-ESC 2013 guidelines. Serum A-FABP levels were measured using a commercial enzyme-linked immunosorbent assay kit. Results Twenty-five (32.9%) of the 76 PD patients were classified in the high arterial stiffness group. Compared with the patients in the low arterial stiffness group, the high arterial stiffness group was older (P = 0.002) and had a longer PD vintage (P = 0.011), higher diastolic blood pressure (DBP, P = 0.036), higher fasting glucose levels (P = 0.012), higher serum C reactive protein levels (P = 0.001), and higher serum A-FABP levels (P < 0.001). A multivariate logistic regression analysis of the factors significantly associated with central arterial stiffness revealed that A-FABP (odds ratio (OR): 1.165, 95% confidence interval (CI): 1.056–1.284, P = 0.002), age (OR: 1.423, 95% CI: 1.153–1.757, P = 0.001), PD vintage (OR: 1.049, 95% CI: 1.015–1.085, P = 0.005), and DBP (OR: 1.152, 95% CI: 1.033–1.285, P = 0.011) were independent predictors of central arterial stiffness in PD patients. Furthermore, serum A-FABP levels (β = 0.476, adjusted R2 change: 0.197, P < 0.001) were significantly positively correlated with cfPWV according to the multivariable forward stepwise linear regression analysis. Conclusions A-FABP levels are an independent marker of central arterial stiffness in PD patients.

Association of adipocyte fatty acid-binding protein and tumor necrosis factor alpha with periodontal health and disease: A cross-sectional investigation.

Background:Adipocyte fatty acid binding protein (A-FABP) is a novel biomarker of inflammation for various chronic systemic diseases. Since periodontitis is a chronic inflammatory disease, this study explores the association of A-FABP with periodontal disease parameters and tumor necrosis factor-alpha (TNF-α) levels in gingival crevicular fluid in periodontal health and disease.Materials and Methods:This original research article describes a cross-sectional study conducted at the Department of Periodontics, M. R. Ambedkar Dental College and Hospital, Bangalore, India. This cross-sectional investigation was conducted on sixty subjects which were divided into three groups of twenty subjects each – healthy, gingivitis, and chronic periodontitis. Clinical parameters – plaque index, bleeding index, probing depth, and clinical attachment loss were recorded. Gingival crevicular fluid samples were analyzed for A-FABP and TNF-α levels using ELISA. One-way analysis of variance was used to find the significance of study parameters on a continuous scale between three groups. Pearson's correlation has been used to find the relationship between Gingival crevicular fluid concentration of markers and periodontal parameters. Multiple linear regression analysis was applied to the study. The statistical significance was considered at P < 0.05.Results:Mean concentration of A-FABP (6.43 ± 2.51) and TNF-α (3454.82 ± 1566.44) was highest in the periodontitis group, and the difference among the groups was statistically significant (P < 0.05). A positive correlation was observed between clinical attachment loss and the two markers among all groups. The correlation between A-FABP and TNF-α in periodontitis groups was positive and statistically significant (P < 0.05). Multiple linear regression model was statistically significant (P < 0.05) indicating that there is a significant relationship between the set of predictors and the clinical attachment loss.Conclusion:A-FABP and TNF-α levels in GCF were significantly elevated in the presence of inflammation. A-FABP has a probable stimulatory effect on TNF-α; however, its role needs to be explored. A-FABP could serve as a novel inflammatory biomarker of periodontitis and the scope of using A-FABP inhibition as a treatment modality could be investigated with interventional studies.