FABP4 Concentrations Research Articles

Association of circulating adipokines with metabolic measures among people with HIV: Moderating effects of alcohol use.

People with HIV (PWH) are at increased risk for cardiometabolic comorbidities. We have reported that lifetime alcohol use among people with HIV (PWH) is associated with increased risk for metabolic syndrome. Dysfunctional adipose tissue and altered circulating adipokines mediate metabolic dysregulation. The objective of this study was to determine the associations of circulating adipokine concentration with metabolic measures, and the moderating effects of lifetime and recent alcohol use in PWH. This is a cross-sectional analysis of data from 357 PWH at their baseline visit of the longitudinal New Orleans Alcohol and HIV (NOAH) study. The concentrations of four circulating adipokines (adiponectin, leptin, resistin, and fatty acid-binding protein 4 [FABP4]) and their associations with five metabolic measures (triglycerides, cholesterol, Hemoglobin A1c, Homeostatic Model Assessment for Insulin Resistance, and metabolic syndrome) were examined. Higher circulating adiponectin was associated with increased odds of normal triglyceride, cholesterol, and Hemoglobin A1c levels. Increased leptin and FABP4 concentrations were associated with decreased odds of normal triglyceride and cholesterol levels. Increased leptin and FABP4 concentrations were associated with increased odds of insulin resistance and meeting criteria for metabolic syndrome. Increased circulating resistin concentration was associated with decreased odds of normal triglyceride levels and increased odds of meeting criteria for metabolic syndrome. Additionally, among PWH with increased lifetime alcohol use, higher adiponectin concentration was associated with decreased odds of meeting criteria for metabolic syndrome. These data suggest the interplay between adiponectin, leptin, FABP4, and resistin may contribute to metabolic stability among PWH. Moreover, lifetime, but not recent, alcohol use moderates the relationship between adipokines and metabolic measures. These data highlight the relevance of functional adipose tissue mass and associated circulating adipokine levels in maintaining metabolic homeostasis, and its moderation by lifetime alcohol consumption.

SIRT3/AMPK Signaling Pathway Regulates Lipid Metabolism and Improves Vulnerability to Atrial Fibrillation in Dahl Salt-Sensitive Rats.

Hypertension may result in atrial fibrillation (AF) and lipid metabolism disorders. The Sirtuins3 (SIRT3)/AMP-activated protein kinase (AMPK) signaling pathway has the capacity to regulate lipid metabolism disorders and the onset of AF. We hypothesize that the SIRT3/AMPK signaling pathway suppresses lipid metabolism disorders, thereby mitigating salt-sensitive hypertension (SSHT)-induced susceptibility to AF. The study involved 7-week-old male Dahl salt-sensitive that were fed either a high-salt diet (8% NaCl; DSH group) or a normal diet (0.3% NaCl; DSN group). Then DSH group was administered either oral metformin (MET, an AMPK agonist) or intraperitoneal injection of Honokiol (HK, a SIRT3 agonist). This experimental model allowed for the measurement of Systolic blood pressure (SBP), the expression levels of lipid metabolism-related biomarkers, pathological examination of atrial fibrosis, and lipid accumulation, as well as AF inducibility and AF duration. DSH decrease SIRT3, phosphorylation-AMPK, and very long-chain acyl-CoA dehydrogenase, (VLCAD) expression, increased FASN and FABP4 expression and concentrations of free fatty acid and triglyceride, atrial fibrosis and lipid accumulation in atrial tissue, enhanced level of SBP, promoted AF induction rate and prolonged AF duration, which are blocked by MET and HK. Our results also showed that the degree of atrial fibrosis was negatively correlated with VLCAD expression, but positively correlated with the expression of FASN and FABP4. We have confirmed that a high-salt diet can result in hypertension, and associated atrial tissue lipid metabolism dysfunction. This condition is linked to the inhibition of the SIRT3/AMPK signaling pathway, which plays a significant role in the progression of susceptibility to AF in SSHT rats.

The Concept of Stroma AReactive Invasion Front Areas (SARIFA) as a new prognostic biomarker for lipid-driven cancers holds true in pancreatic ductal adenocarcinoma

BackgroundPancreatic ductal adenocarcinoma (PDAC) is a ‘difficult-to-treat’ entity. To forecast its prognosis, we introduced a new biomarker, SARIFA (stroma areactive invasion front areas), which are areas at the tumour invasion front lacking desmoplastic stroma reaction upon malignant invasion in the surrounding tissue, leading to direct contact between tumour cells and adipocytes. SARIFA showed its significance in gastric and colorectal carcinoma, revealing lipid metabolism alternations that promote tumour progression.MethodsWe reviewed the SARIFA status of 166 PDAC cases on all available H&E-stained tumour slides from archival Whipple-resection specimens. SARIFA positivity was defined as SARIFA detection in at least 66% of the available slides. To investigate alterations in tumour metabolism and microenvironment, we performed immunohistochemical staining for FABP4, CD36 and CD68. To verify and quantify a supposed delipidation of adipocytes, adipose tissue was digitally morphometrised.ResultsIn total, 53 cases (32%) were classified as SARIFA positive and 113 (68%) as SARIFA negative. Patients with SARIFA-positive PDAC showed a significantly worse overall survival compared with SARIFA-negative cases (median overall survival: 11.0 months vs. 22.0 months, HR: 1.570 (1.082–2.278), 95% CI, p = 0.018), which was independent from other prognostic markers (p = 0.014). At the invasion front of SARIFA-positive PDAC, we observed significantly higher expression of FABP4 (p < 0.0001) and higher concentrations of CD68+ macrophages (p = 0.031) related to a higher risk of tumour progression. CD36 staining showed no significant expression differences. The adipocyte areas at the invasion front were significantly smaller, with mean values of 4021 ± 1058 µm2 and 1812 ± 1008 µm2 for the SARIFA-negative and -positive cases, respectively (p < 0.001).ConclusionsSARIFA is a promising prognostic biomarker for PDAC. Its assessment is characterised by simplicity and low effort. The mechanisms behind SARIFA suggest a tumour-promoting increased lipid metabolism and altered immune background, both showing new therapeutic avenues.

Investigating the Role of FABP4 in Diabetes and Obesity and the Influence of Age and Ethnicity: A Comprehensive Analysis of a Cohort from the KEDP-Study.

Adipocyte P2 (aP2), also known as FABP4, is an adipokine that adipose tissue produces and expresses in macrophages. Its primary role is to facilitate the transportation of fatty acids across cell membranes. Numerous studies have reported associations between FABP4 and the development of metabolic disorders. However, there is limited knowledge regarding FABP4 expression in diabetes and obesity, especially about different age groups, genders, and ethnicities. This study aims to investigate the association between FABP4 levels, diabetes mellitus, and obesity within various ethnic groups. We measured plasma FABP4 concentrations in a cohort of 2083 patients from the KDEP study and gathered anthropometric data. Additionally, we collected and analyzed clinical, biochemical, and glycemic markers using multivariate regression analysis. The average FABP4 concentration was significantly higher in female participants than in males (18.8 ng/mL vs. 14.4 ng/mL, p < 0.001, respectively), and in those over 50 years old compared to those under 50 years of age (19.3 ng/mL vs. 16.2 ng/mL, p < 0.001, respectively). In this study, significant positive associations were found between the plasma level of FABP4 and obesity markers: BMI (r = 0.496, p < 0.001), hip circumference (r = 0.463, p < 0.001), and waist circumference (WC) (r = 0.436, p < 0.001). Similar observations were also seen with glycemic markers, which included HbA1c (r = 0.126, p < 0.001), fasting blood glucose (FBG) (r = 0.184, p < 0.001), fasting insulin (r = 0.326, p < 0.001), and HOMA-IR (r = 0.333, p < 0.001). Importantly, these associations remained significant even after adjusting for age, gender, and ethnicity. Furthermore, FABP4 levels were negatively associated with male gender (β: -3.85, 95% CI: -4.92, -2.77, p < 0.001), and positively associated with age (β: 0.14, 95% CI: 0.096, 0.183, p < 0.001), BMI (β: 0.74, 95% CI: 0.644, 0.836, p < 0.001), and fasting insulin (β: 0.115, 95% CI: 0.091, 0.138, p < 0.001). In this study, plasma FABP4 levels were significantly higher in diabetic and obese participants, and they were strongly influenced by age, gender, and ethnicity. These findings suggest that FABP4 may serve as a valuable prognostic and diagnostic marker for obesity and diabetes, particularly among female patients, individuals over 50 years old, and specific ethnic groups.

Carbohydrate ingestion does not suppress increases in fatty acid-binding protein 4 concentrations post-acute aerobic exercise in healthy men: a randomized crossover study

BackgroundFatty acid-binding protein 4 (FABP4) has been associated with cardiovascular disease and diabetes. Acute aerobic exercise increases circulating FABP4 concentrations, but the underlying mechanisms remain unclear. The purpose of this study was to investigate the effects of inhibition of lipolysis by carbohydrate ingestion on circulating FABP4 concentrations during and after acute aerobic exercise in healthy men.MethodsMen aged between 20 and 40, with no exercise habits and no metabolic diseases, were recruited. In a randomized crossover design, the participants underwent a carbohydrate-ingestion exercise (CE) and a fasted exercise (FE) trial. The CE trial consisted of 40-min acute aerobic exercise with ingestion of carbohydrates and 60-min bed rest. The FE trial followed the same protocol as the CE trial but without carbohydrate ingestion. Venous blood samples were collected to measure hormones (adrenaline, noradrenaline, and insulin) metabolites (glycerol, free fatty acids, and glucose), and FABP4 concentrations. Ventilation and gas exchange were also collected to measure substrate oxidation.ResultsThirteen healthy men participated in and completed both the CE and FE trials. The insulin concentration was more than 4 times higher in the CE trial than in the FE trial (p < 0.004, effect size [ES] > 2.00). Free fatty acid concentrations were more than 4 times lower in the CE trial than in the FE trial (p < 0.02, ES > 2.04). However, there was no significant difference in the changes in circulating FABP4 concentrations between the CE and FE trials (p = 0.108), which did not change during aerobic exercise and significantly increased post-aerobic exercise in both trials (p < 0.002, ES > 1.212). Changes in FABP4 concentrations following aerobic exercise were not significantly correlated with changes in glycerol or free fatty acid concentrations during aerobic exercise.ConclusionsThe results suggest that suppression of lipolysis and elevation of insulin are not strongly involved in increases in FABP4 secretion following acute aerobic exercise.

High FABP4, associated with low-voltage areas, increases the epicardial fibrosis and its glucose metabolism

Abstract Background High plasma levels of FABP4 were associated with epicardial fat volume on persistent AF patients. FABP4 can be released by differentiated adipocytes and macrophages, which can be involved in fibrosis. Purpose Our main objective was to study the association between FABP4 and epicardial fibrosis, which can explain low-voltage areas (LVA) and atrial fibrillation (AF) recurrence. Material and methods Peripheral levels of FABP4 and Galectin-3 were analysed on AF patients undergoing pulmonary vein isolation (PVI) (n=299) and signed informed consent. During the intervention, LVA was evaluated by invasive electroanatomic voltage mapping (EAM). Epicardial (EAT) (n=6) and subcutaneous adipose tissue (SAT) (n=5) were obtained from undergoing open heart surgery patients. Stromal cells were isolated by collagenase digestion, cultured and treated with and without FABP4 100 ng/mL and/or galectin-3 30 ng/mL for 24 hours. The proliferation and migration rate were measured by wound healing assay; mitochondrial activity was studied by MTT assay; and glucose and lactate consumption were detected by colorimetric and fluorescence enzymatic assays, respectively. Gene expression levels were assessed by real-time PCR. Results Regression analysis determined that the main independent predictors of LVA were age, left atrial area and FABP4 levels. Preclinical "in vitro" studies have shown that FABP4 100 ng/mL induced fibrosis in epicardial stromal cells (p=0.0039) and subcutaneous stromal cells (p=0.0009), evidenced by wound healing assay and by the increment of associated fibroblast genes (COL1A2, VIM, TGF-β1). Moreover, the high FABP4 concentration modulates the protein levels and metabolic genes expression (CPT1, FASN, ATGL, related to transport, synthesis and degradation of fatty acids, respectively) on EAT stromal cells. Glucose metabolism without lactate production was also incremented after FABP4 treatment (p&amp;lt;0.0001). Even, on SAT cells, released lactate was reduced after FABP4 treatment (p=0.0218). Conclusions Plasma FABP4 was a predictor of LVA. Our results suggest that this association might be explained by the fibrotic and metabolic role of FABP4 in epicardial cells. Future studies will shed light on the benefits on atrial remodelling with FABP4 modulators.Figure 1Figure 2

Circulating fatty acid-binding protein 4 response to acute aerobic exercise in healthy men.

This study aimed to investigate the association between changes in FABP4 concentration and hormones and metabolites levels during and after acute low- and moderate-intensity aerobic exercise in healthy men. Eleven healthy men (24.4 ± 1.4 years) were administered three trials in random order: 1) low-intensity aerobic exercise trial (LE trial; acute exercise at 40% peak oxygen uptake [Vo2peak] + bed rest), 2) moderate-intensity aerobic exercise trial (ME trial: acute exercise at 60%Vo2peak + bed rest), and 3) bed rest (Con trial). Expired gas and venous blood samples were collected at baseline, and immediately, 30 and 60 min after exercise, and substrate oxidation and hormone, metabolite, and FABP4 concentrations were measured. FABP4 concentration did not increase during aerobic exercise in LE and ME trials (p > 0.05) However, FABP4 concentration significantly increased after the acute aerobic exercise in both the LE and ME trials (p ≤ 0.003). Increased FABP4 concentration after acute exercise was not correlated with adrenaline, noradrenaline, other hormone, and metabolite concentration changes. These findings suggest that FABP4 concentration increases after acute aerobic exercise independently of exercise intensity. Furthermore, increased FABP4 concentration after acute aerobic exercise may not be involved in the magnitude of adrenaline, noradrenaline, and lipolytic response.

Fatty Acid Binding Proteins 3 and 4 Predict Both All-Cause and Cardiovascular Mortality in Subjects with Chronic Heart Failure and Type 2 Diabetes Mellitus

Subjects with type 2 diabetes mellitus (T2D) are at increased risk for heart failure (HF). The cardiac-specific (FABP3) and adipose-tissue-specific (FABP4) types of the fatty acid binding proteins have been associated with both all-cause and cardiovascular (CV) mortality. The aim of this study was to explore the prognosis value of FABP3 and FABP4 in ambulatory subjects with chronic HF (CHF), with and without T2D. A prospective study involving 240 ambulatory CHF subjects was performed. Patients were followed-up for a mean of 5.78 ± 3.30 years and cause of death (if any) was recorded. Primary endpoints were defined as all-cause and CV death, and a composite endpoint that included CV death or hospitalization for HF was included as a secondary endpoint. Baseline serum samples were obtained and the serum FABP3 and FABP4 concentrations were assessed by sandwich enzyme-linked immunosorbent assay. Survival analysis was performed with multivariable Cox regressions, using Fine and Gray competing risks models when needed, to explore the prognostic value of FABP3 and FABP4 concentrations, adjusting for potential confounders. Type 2 diabetes mellitus was highly prevalent, accounting for 47.5% for total subjects with CHF. Subjects with T2D showed higher mortality rates (T2D: 69.30%; non-T2D: 50.79%, p = 0.004) and higher serum FABP3 (1829.3 (1104.9-3440.5) pg/mL vs. 1396.05 (820.3-2362.16) pg/mL, p = 0.007) and FABP4 (45.5 (27.6-79.8) ng/mL vs. 34.1 (24.09-55.3) ng/mL, p = 0.006) concentrations compared with non-T2D CHF subjects. In the whole study cohort, FABP3 was independently associated with all-cause death, and both FABP3 and FABP4 concentrations were associated with CV mortality. The predictive values of these two molecules for all-cause (FABP3: HR 1.25, 95% CI 1.09-1.44; p = 0.002. FABP4: HR 2.21, 95% CI 1.12-4.36; p = 0.023) and CV mortality (FABP3: HR 1.28, 95% CI 1.09-1.50; p = 0.002. FABP4: HR 4.19, 95% CI 2.21-7.95; p < 0.001) were only statistically significant in the subgroup of subjects with T2D. Notably, FABP4 (HR 2.07, 95% CI 1.11-3.87; p = 0.022), but not FABP3, also predicted the occurrence of the composite endpoint (death or hospitalization for HF) only in subjects with T2D. All these associations were not found in CHF subjects without T2D. Our findings support the usefulness of serum FABP3 and FABP4 concentrations as independent predictors for the occurrence of all-cause and CV mortality in ambulatory subjects with CHF with T2D.

The Relationship Between the Level Fabp4, Risks of Type 2 Diabetes Mellitus, and Cardiovascular Events

BACKGROUND: The normoglycemic patients with diabetes risk and prediabetes have insulin resistance and consequently endothelial dysfunction that possible causes macroangiopathy and adverse cardiovascular events and further mortality of it. An early diabetes risk identification using not only prognostic scales but also biomarkers is starting and crucial point of struggle with 2 type diabetes mellitus and its complications.&#x0D; AIM: The aim of the study is to estimate the impact of FABP4 biomarker on diabetes risk and cardiovascular events.&#x0D; METHODS: A cross-sectional study was conducted simultaneously among 389 respondents aged 18–65 years. We provided survey and clinical examinations. The risk of diabetes was assessed using the FINDRISC scale and cardiovascular risk (CVR) was assessed using SCORE scale.&#x0D; The serum FABP4 biomarker was studied using a multiplex assay, immunofluorescence using XMap technology, a Bioplex 3D instrument, and a MILLIPLEX® Human cardiovascular disease panel I reagent kit(Millipore). Results were considered statistically significant at p &lt; 0.001.&#x0D; RESULTS: The group of type 2 diabetes mellitus (T2DM) high risk was 79 (20%) of all study participants. The level of the FABP4 marker significantly prevailed in high-risk group of T2DM and high CVR was also established this group. We found a positive direct average correlation(r = 0.59; p = 0.000) between FABP4 and FINDRISC scale. The logistic regression analysis indicated that the level of the FABP4 marker increases withing the increased risk of T2DM. The correlation between FABP4 concentration and CVR according to the SCORE scale (r = 0.24; p = 0,000) was lower than between FABP4 and diabetes risk. Risk factors were established affecting on the increasing CVR by SCORE scale in patients with T2DM risk.&#x0D; CONCLUSIONS: The level of FABP4 significantly prevailed in the group of diabetes and cardiovascular risk (CVR). The established correlations between FABP4 level and CVR or T2DM risk indicate on its increase in groups with a higher risk of type 2 diabetes and a high CVR.

Treatment with anagliptin, a DPP-4 inhibitor, decreases FABP4 concentration in patients with type 2 diabetes mellitus at a high risk for cardiovascular disease who are receiving statin therapy

BackgroundFatty acid-binding protein 4 (FABP4) acts as a novel adipokine, and elevated FABP4 concentration is associated with obesity, insulin resistance and atherosclerosis. Dipeptidyl peptidase-4 (DPP-4) inhibitors, a class of antidiabetic drugs, have distinct structures among the drugs, possibly leading to a drug class effect and each drug effect. Sitagliptin, a DPP-4 inhibitor, has been reported to decrease FABP4 concentration in drug-naïve and sulfonylurea-treated patients with type 2 diabetes mellitus. Anagliptin, another DPP-4 inhibitor, was shown to decrease low-density lipoprotein cholesterol (LDL-C) level to a greater extent than that by sitagliptin in the Randomized Evaluation of Anagliptin vs. Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) trial.Aim and methodsAs a sub-analysis study using data obtained from the REASON trial, we investigated the effects of treatment with anagliptin (n = 148, male/female: 89/59) and treatment with sitagliptin (n = 159, male/female: 93/66) for 52 weeks on FABP4 concentration in patients with type 2 diabetes mellitus at a high risk for cardiovascular events who were receiving statin therapy.ResultsThe DPP-4 inhibitor had been administered in 82% of the patients in the anagliptin group and 81% of the patients in sitagliptin group prior to randomization. Serum FABP4 level was significantly decreased by 7.9% by treatment with anagliptin (P = 0.049) and was not significantly decreased by treatment with sitagliptin (P = 0.660). Change in FABP4 level was independently associated with basal FABP4 level and changes in waist circumference and creatinine after adjustment of age, sex and the treatment group.ConclusionAnagliptin decreases serum FABP4 concentration independent of change in hemoglobin A1c or LDL-C in patients with type 2 diabetes mellitus and dyslipidemia who are on statin therapy.Trial registration ClinicalTrials.gov number NCT02330406. Registered January 5, 2015, https://clinicaltrials.gov/ct2/show/NCT02330406

Adipocyte Fatty Acid-Binding Protein as a Novel Marker of Psoriasis and Clinical Response to Acitretin.

Psoriasis is a systemic disease associated with metabolic syndrome and cardiometabolic diseases. Adipocyte fatty acid-binding protein (A-FABP, FABP4) is a relevant mediator of lipid metabolism and several comorbidities development. Aim of the study was to explore the possible role of FABP4 in psoriasis and assess its relationship with disease activity, inflammation or metabolic disturbances, and impact of systemic treatment. Fasting blood samples were obtained from 33 patients with active plaque-type psoriasis before and after 12 weeks of therapy and from 11 healthy volunteers. Serum FABP4 concentrations were analyzed by the enzyme-linked immunosorbent assay (ELISA) and statistically analyzed for their correlations with clinical outcomes and the treatment introduced. Serum FABP4 levels were significantly increased in psoriatics compared to controls (p = 0.03). No relationship between the protein and psoriasis severity expressed through psoriasis area and severity index (PASI) was noted (p = 0.57). FABP4 did not correlate with CRP (p = 0.41), lipid profile, and body mass index (BMI) nor the glucose level or liver enzyme activity. FABP4 significantly correlated with morphotic blood elements. After total therapy, FABP4 did not statistically change (p = 0.07), but significantly decreased after administering acitretin (p = 0.03). FABP4 is a potential marker of psoriasis and clinical outcome after therapy with acitretin. Adipocyte-type FABP may be related to hematological disorders or obesity-mediated comorbidities in psoriasis.

Atherogenic Index of Plasma: Novel Predictive Biomarker for Cardiovascular Illnesses

Cardiovascular diseases (CVD) are the most important cause of mortality globally. Nevertheless, the World Health Organization have declared that a precise and quick recognition of susceptible individuals to develop CVD is imperative to combat those illnesses. Additionally, developing countries need affordable alternatives to effectively prognosticate cardiovascular events. Therefore, the objective of this study was to assess well-established clinical prognostic markers in Mexican women to identify affordable, specific, and useful tools to predict cardiovascular events. A cross-sectional study was performed including 340 healthy women. Anthropometric and clinical measurements were acquired from all enrolled individuals. Also, a blood sample of each participant women was obtained to complete biochemical analyses (triglycerides, glucose, total cholesterol, LDL cholesterol, and HDL cholesterol), and serum asymmetric dimethylarginine (ADMA), and adipocyte-fatty acid binding protein (FABP4) determinations. Finally, with anthropometric, clinical and biochemical determinations, atherogenic indices (Framingham risk score, Castelli's risk index, and atherogenic index of plasma) were estimated. A mean value of 6.5±7.2 was detected for the Framingham risk score, 3.7±1.3 for Castelli's risk index, and 0.12±0.22 for the atherogenic index of plasma (AIP). Circulating mean ADMA and FABP4 levels found in assessed women were 0.68±0.34mmol/L and 20.3±16.6ng/mL, respectively. Furthermore, strong positive relationships (p <0.05) between AIP and serum FABP4 and ADMA concentrations were detected after adjustment by traditional CVD risk factors. In conclusion, AIP could be recommended as a potential biomarker in the early diagnosis of CVD events in developing countries.

Serum FABP4 concentrations decrease after Roux-en-Y gastric bypass but not after intensive medical management

BackgroundSerum concentrations of fatty acid binding protein 4, an adipose tissue fatty acid chaperone, have been correlated with insulin resistance and cardiovascular risk factors. The objective of this study were to assess relationships among Roux-en-Y gastric bypass, intensive lifestyle modification and medical management protocol, fatty acid binding protein 4, and metabolic parameters in obese patients with severe type 2 diabetes mellitus; and to evaluate the relative contribution of abdominal subcutaneous adipose and visceral adipose to the secretion of fatty acid binding protein 4. MethodsParticipants were randomly assigned to intensive lifestyle modification and medical management protocol (n = 29) or to intensive lifestyle modification and medical management protocol augmented with Roux-en-Y gastric bypass (n = 34). Relationships among fatty acid binding protein 4 and demographic characteristics, metabolic parameters, and 12-month changes in these values were examined. Visceral and subcutaneous adipose tissue explants from obese nondiabetic patients (n = 5) were obtained and treated with forskolin to evaluate relative secretion of fatty acid binding protein 4 in the different adipose tissue depots. ResultsThe intensive lifestyle modification and medical management protocol and Roux-en-Y gastric bypass cohorts had similar fasting serum fatty acid binding protein 4 concentrations at baseline. At 1 year, mean serum fatty acid binding protein 4 decreased by 42% in Roux-en-Y gastric bypass participants (P = .002) but did not change significantly in the intensive lifestyle modification and medical management protocol cohort. Percentage of weight change was not a significant predictor of 12-month fatty acid binding protein 4 within treatment arm or in multivariate models adjusted for treatment arm. In adipose tissue explants, fatty acid binding protein 4 was secreted similarly between visceral and subcutaneous adipose tissue. ConclusionAfter Roux-en-Y gastric bypass, fatty acid binding protein 4 is reduced 12 months after surgery but not after intensive lifestyle modification and medical management protocol in patients with type 2 diabetes mellitus. Fatty acid binding protein 4 was secreted similarly between subcutaneous and visceral adipose tissue explants.

Decreased serum fatty acid binding protein 4 concentrations are associated with sarcopenia in chronic hemodialysis patients

BackgroundFatty acid binding protein 4 (FABP4) is found to play a role in skeletal muscle homeostasis. Since the dysregulation of FABP4 and sarcopenia are both highly prevalent in patients on chronic hemodialysis (HD), the correlation between them remains unknown. We aimed to examine this relationship in a cross-sectional study. MethodsA total of 120 chronic HD patients were recruited, and whose skeletal muscle mass, handgrip strength, and gait speed were assessed and blood samples were obtained. We grouped these participants into sarcopenia (n = 20) and non-sarcopenia groups according to European Working Group on Sarcopenia in Older People criteria. ResultsThe sarcopenia group exhibited lower weight (P < 0.001), height (P = 0.019), waist circumference (P < 0.001), body mass index (P < 0.001), body fat mass (P = 0.004), and lower serum triglycerides (P = 0.009), creatinine (P < 0.001), phosphorus (P = 0.013), intact parathyroid hormone (P = 0.012), and FABP4 concentrations (P = 0.005), and higher malnutrition–inflammation scores (MIS) (P = 0.031), urea reduction rates (P < 0.001), and fractional clearance index for urea (Kt/V) values (P < 0.001). Serum FABP4 concentrations (odds ratio (OR): 0.98, 95% confidence interval (CI): 0.96–0.99, P = 0.043), body fat mass (OR: 0.86, 95% CI: 0.77–0.97, P = 0.013), MIS (OR: 6.90, 95% CI: 1.31–36.36, P = 0.023), and Kt/V (each increase of 0.1, OR: 2.15, 95% CI: 1.29–3.57, P = 0.003) were independent predictors of sarcopenia in chronic HD patients. ConclusionsWe delineated the association between serum FABP4 concentrations and sarcopenia in chronic HD patients.

Lack of pronounced changes in the expression of fatty acid handling proteins in adipose tissue and plasma\xa0of morbidly obese humans

Background/ObjectivesFatty acid handling proteins are involved in the process of accumulation of lipids in different fat tissue depots. Thus, the aim of the study was to estimate the expression of both fatty acid transport and binding proteins in the subcutaneous (SAT) and visceral adipose tissue (VAT) of patients with morbid obesity without metabolic syndrome, as well as the plasma concentrations of these transporters.Subjects/MethodsProtein (Western blotting) and mRNA (Real-time PCR) expression of selected fatty acid handling proteins was assessed in the visceral and subcutaneous adipose tissue of 30 patients with morbid obesity. The control group consisted of 10 lean age-matched patients. Plasma levels of fatty acid protein transporters were also evaluated using ELISA method. Moreover, total plasma fatty acid composition and concentration was determined by gas-liquid chromatography (GLC).ResultsSignificant increase in fatty acid translocase (FAT/CD36) mRNA (P = 0.03) and plasmalemmal (P = 0.01) expression was observed in VAT of patients with morbid obesity vs. lean subjects together with elevation of lipoprotein lipase (LPL), as well as peroxisome proliferator-activated receptor γ (PPARγ) in both examined compartments of adipose tissue. Moreover, in obese subjects plasma concentration of RBP4 was markedly elevated (P = 0.04) and sCD36 level presented a tendency for an increase (P = 0.08) with concomitant lack of changes in FABP4 concentration (P > 0.05).ConclusionsFatty acid transport into adipocytes may be, at least in part, related to the increased expression of FAT/CD36 in the VAT of morbidly obese patients, which is accompanied by augmented expression of LPL, as well as PPARγ. Probably, alternations in plasma concentrations of RBP4 and sCD36 in obese patients are associated with “unhealthy” fat distribution.

Serum Concentrations of New Predictive Cardiovascular Disease Biomarkers in Mexican Women Exposed to Lead.

The purpose of this study was to evaluate lead exposure and its relationship with serum levels of predictive CVD biomarkers [asymmetric dimethylarginine (ADMA), adipocyte fatty acid-binding protein (FABP4), adiponectin, and chemerin] in women living in San Luis Potosi, Mexico. A mean blood lead level (BLL) of 11.5±9.00μg/dL (mean±standard deviation) was found after all blood samples were analyzed. Regarding serum predictive CVD biomarkers, mean serum level of 0.68±0.38μmol/L, 20.5±16.5ng/mL, 12.5±3.30μg/mL, and 255±130ng/mL were found for ADMA, FABP4, adiponectin, and chemerin, respectively. Simple significant associations (Pearson´s correlations) between BLL and ADMA (r=0.17; p=0.04) and FABP4 (r=0.23; p=0.03) were found. Furthermore, a multivariate linear regression model showed that BLL was a significant predictor of serum ADMA (β=0.06; p=0.001) and FABP4 (β=1.75; p=0.0004) concentrations after adjusting by confounders. For serum chemerin and adiponectin levels, no associations were found with BLL. In conclusion, high serum ADMA and FABP4 (predictive CVD biomarkers) levels were found in women exposed to lead. Consequently, this research can be used as a point of departure for the prevention of CVD events in populations living in sites environmentally impacted with lead.

Serum adipocyte-fatty acid binding protein (FABP4) levels in women from Mexico exposed to polycyclic aromatic hydrocarbons (PAHs).

Recent studies indicate that exposure to polycyclic aromatic hydrocarbons (PAHs) is a very important risk factor for the development of cardiovascular diseases (CVDs). Correspondingly, adipocyte-fatty acid binding protein (FABP4, also known as aP2 and AFABP) has been proposed as a new, meaningful and useful biomarker to predict metabolic and cardiovascular diseases. Therefore, the aim of this study was to evaluate serum FABP4 levels in Mexican women exposed to PAHs. Urinary 1-hydroxypyrene ((1-OHP), exposure biomarker for PAHs) levels were quantified using a high-performance liquid chromatography (HPLC) technique, and serum FABP4 concentrations were analyzed using a commercially available ELISA kit. The mean urinary 1-OHP level found in women participating in this study was 1.30±1.10μmol/mol creatinine (2.45±2.10μg/g creatinine). Regarding serum FABP4 concentrations, the levels ranged from 3.80 to 62.5ng/mL in the assessed population. Moreover, a significant association (p<0.001) was found between urinary 1-OHP levels and serum FABP4 concentrations in women after adjusting for potential confounding variables. The presented data in this study can be considered only as a starting point for further studies. Then, in order to elucidate whether FABP4 represents a risk factor for CVD disease in humans exposed to air contaminants (such as PAHs), large epidemiological studies are necessary.

Independent Link Between Levels of Proprotein Convertase Subtilisin/Kexin Type 9 and FABP4 in a General Population Without Medication

Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to and degrades the low-density lipoprotein (LDL) receptor, leading to hypercholesterolemia and cardiovascular risk. Fatty acid binding protein 4 (FABP4/adipocyte FABP/aP2) is secreted from adipocytes in association with lipolysis, and circulating FABP4 has been reported to act as an adipokine for the development of insulin resistance and atherosclerosis. Elevated serum FABP4 level is associated with obesity, insulin resistance, dyslipidemia, and atherosclerosis. In this study, we examined the association between circulating levels of FABP4 and PCSK9 in a general population. A total of 265 subjects (male/female: 98/167) who were not on medication were recruited from subjects of the Tanno-Sobetsu Study, and concentrations of FABP4 and PCSK9 were measured. The level of FABP4, but not that of PCSK9, showed a gender difference, being higher in women than in men. FABP4 level was independently associated with gender, adiposity, renal dysfunction, and levels of cholesterol and PCSK9. There was a significant and gender-different correlation between PCSK9 level and age: negatively in men (r=-0.250, p= 0.013) and positively in women (r= 0.183, p= 0.018). After adjustment of age, gender, and LDL cholesterol level, PCSK9 level was positively and independently correlated with FABP4 concentration. In conclusion, PCSK9 level is differentially regulated by gender during aging. Circulating FABP4 is independently associated with the PCSK9 level, suggesting that elevation of FABP4 level as an adipokine leads to dyslipidemia through increased PCSK9 level and subsequent degradation of the LDL receptor.

FABP4 plasma concentrations are determined by acquired metabolic derangements rather than genetic determinants

Background and aimsCirculating FABP4 is strongly associated with metabolic and cardiovascular risk (CVR) and has been proposed as a new risk biomarker. Several FABP4 gene polymorphisms have been associated with protein expression in vitro and metabolic and vascular alterations in vivo. The aim of this study is to evaluate the impact of FABP4 polymorphisms on FABP4 plasma levels and subclinical arteriosclerosis in patients with obesity, metabolic syndrome (MS) or type 2 diabetes (T2DM). Methods and resultsWe studied 440 individuals with obesity, MS, T2DM or other cardiovascular risk conditions who attended the vascular medicine and metabolism unit of our hospital. Anamnesis, physical examination and anthropometry data were recorded. Standard biochemical parameters were determined. Plasma FABP4 concentrations were measured. Carotid intima-media thickness (cIMT) was assessed using ultrasonography. The following FABP4 gene single-nucleotide polymorphisms (SNPs) were analyzed: rs3834363, rs16909233, rs1054135, rs77878271, rs10808846 and rs8192688. None of the studied gene allele variants were hyper-represented in patients grouped according the presence of metabolic alterations nor were they associated with the FABP4 concentration. The FABP4 gene variants did not determine cIMT differences between the groups. In a multivariate analysis, gender and BMI, but not gene variants, significantly determined plasma FABP4 concentrations. ConclusionsIn clinical settings, the circulating FABP4 levels are determined by the acquired metabolic derangements and not genetic variation.

Angiotensin II receptor blockers decrease serum concentration of fatty acid-binding protein 4 in patients with hypertension.

Elevated circulating fatty acid-binding protein 4 (FABP4/A-FABP/aP2), an adipokine, is associated with obesity, insulin resistance, hypertension and cardiovascular events. However, how circulating FABP4 level is modified by pharmacological agents remains unclear. We here examined the effects of angiotensin II receptor blockers (ARBs) on serum FABP4 level. First, essential hypertensives were treated with ARBs: candesartan (8 mg day(-1); n=7) for 2 weeks, olmesartan (20 mg day(-1); n=9) for 12 weeks, and valsartan (80 mg day(-1); n=94) or telmisartan (40 mg day(-1); n=91) for 8 weeks added to amlodipine (5 mg day(-1)). Treatment with ARBs significantly decreased blood pressure and serum FABP4 concentrations by 8-20% without significant changes in adiposity or lipid variables, though the M value determined by hyperinsulinemic-euglycemic glucose clamp, a sensitive index of insulin sensitivity, was significantly increased by candesartan. Next, alterations in FABP4 secretion from 3T3-L1 adipocytes were examined under several agents. Lipolytic stimulation of the β-adrenoceptor in 3T3-L1 adipocytes by isoproterenol increased FABP4 secretion, and conversely, insulin suppressed FABP4 secretion. However, treatment of 3T3-L1 adipocytes with angiotensin II or ARBs for 2 h had no effect on gene expression or secretion of FABP4 regardless of β-adrenoceptor stimulation. In conclusion, treatment with structurally different ARBs similarly decreases circulating FABP4 concentrations in hypertensive patients as a class effect of ARBs, which is not attributable to blockade of the angiotensin II receptor in adipocytes. Reduction of FABP4 levels by ARBs might be involved in suppression of cardiovascular events.