High Fatty Acid Binding Protein 4 Research Articles

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

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

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

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

High Serum FABP4 Levels are Negatively Associated with the Reversion from Prediabetes to Normal Glucose Tolerance: A 2-Year Retrospective Cohort Community Study.

ObjectiveTo explore the relationship between the level of fatty acid-binding protein 4 (FABP4) and reversion from prediabetes to normal glucose tolerance (NGT).MethodsA two-year retrospective cohort study was conducted on 398 participants with complete information. These 398 participants were divided into an NGT group and an abnormal glucose metabolism (AGM) group after 2 years of follow-up. The baseline level of FABP4 was determined, and the role of FABP4 in predicting reversion from prediabetes to NGT was investigated using an unconditional logistic regression model.ResultsOver the two-year follow-up period, 37.4% (149/398) of the participants reverted from prediabetes to NGT. The participants with AGM had a higher baseline level of FABP4 than those with NGT. The baseline level of FABP4 was significantly negatively correlated with reversion from prediabetes to NGT. After adjusting for age, sex, body mass index and waist-to-hip ratio, the level of fasting blood glucose (FBG) [odds ratio (OR) 0.336, 95% confidence interval (CI) (0.196–0.576)], 2-h post-challenge blood glucose (2hBG) [OR 0.697, 95% CI (0.581–0.837)], and FABP4 [OR 0.960, 95% CI (0.928–0.993)] at baseline were significant independent predictors of reversion from prediabetes to NGT. The area under the curve (AUC) value of the receiver operating characteristic curve for FABP4 was 0.605 (95% CI: 0.546–0.665), and the AUC for FABP4 combined with FBG and 2hBG was 0.716 (95% CI: 0.663–0.769).ConclusionA higher baseline level of FABP4 was positively correlated with an adverse profile of diabetes risk factors and negatively correlated with reversion from prediabetes to NGT. FABP4, FBG and 2hBG were predictors of reversion from prediabetes to NGT.

The peroxisome proliferator-activated receptor agonist rosiglitazone specifically represses tumour metastatic potential in chromatin inaccessibility-mediated FABP4-deficient gastric cancer.

Background: Efforts to prevent recurrence in gastric cancer (GC) patients are limited by current incomplete understanding of the pathological mechanisms. The present study aimed to identify novel tumour metastasis-associated genes and investigate potential value of these genes in clinical diagnosis and therapy.Methods: RNA sequencing was performed to identify differentially expressed genes related to GC metastasis. The expression and prognostic significance of fatty acid binding protein 4 (FABP4) were evaluated in two independent cohorts of GC patients. Chromatin immunoprecipitation sequencing, diverse mouse models and assays for transposase-accessible chromatin with high-throughput sequencing were used to investigate the roles and mechanisms of action of FABP4.Results: The results of the present multicentre study confirmed an association between a decrease in the expression of FABP4 and poor outcomes in GC patients. FABP4 inhibited GC metastasis but did not influence tumour growth in vitro and in vivo. Mechanistically, FABP4 binding with peroxisome proliferator-activated receptor γ (PPAR-γ) facilitated the translocation of PPAR-γ to the nucleus. FABP4 depletion suppressed PPAR-γ-mediated transcription of cell adhesion molecule 3 (CADM3), which preferentially governed GC metastasis. Notably, the PPAR-γ agonist rosiglitazone reversed the metastatic properties of FABP4-deficient GC cells in vitro and demonstrated viable therapeutic potential in multiple mouse models. For GC patients with diabetes, low FABP4 portends better prognosis than high FABP4 after receipt of rosiglitazone treatment. Additionally, chromatin inaccessibility induced by HDAC1 reduced FABP4 expression at the epigenetic level.Conclusions: Our findings suggest that chromatin inaccessibility orchestrates a reduction in FABP4 expression, which inhibits CADM3 transcription via PPAR-γ, thereby resulting in GC metastasis. The antidiabetic drug rosiglitazone restores PPAR-γ/CADM3 activation in FABP4-deficient GC and thus has promising therapeutic potential.

Fatty acid-binding protein 4 circulating levels in non-segmental vitiligo

BackgroundVitiligo is an acquired and progressive mucocutaneous disease resulting from the loss of active epidermal melanocytes. Metabolic syndrome (MetS) affects about 25% of the world’s population and is linked to inflammatory skin diseases including vitiligo. Fatty Acid-Binding Protein 4 (FABP4) is an intracellular lipid chaperone. FABP4 is closely associated with MetS. ObjectivesTo evaluate the serum level of FABP4 in vitiligo patients and its relation to MetS in the investigated cases. MethodsThis case control study was conducted on 45 patients having non segmental vitiligo and 45 matched controls. Their lipid profile, blood glucose and serum FABP4 levels were measured. ResultsThere were significant elevations in FABP4 (p < 0.001), cholesterol (p < 0.001), triglycerides (p = 0.005), and glucose (fasting [p = 0.001] and 2 hours post prandial [p < 0.001]) levels in patients in comparison with controls. MetS was significantly more prevalent among vitiligo patients (p < 0.001) and associated with high FABP4 serum levels (p = 0.037). In vitiligo patients, there were significant positive correlations between FABP4 serum levels and triglycerides (p = 0.047), cholesterol (p = 0.001) and LDL (p = 0.001) levels and negative correlation regarding HDL level (p = 0.009). FABP4 level was a significantly good diagnostic test for early detection of vitiligo (p < 0.001). Study limitationsThe small number of studied subjects. ConclusionsFABP4 may play an active role in the disease process of vitiligo that could be mediated through associated dyslipidemia and hyperglycemia. FABP4 may be a marker of vitiligo helping in its early diagnosis, but it does not appear to be useful for determining vitiligo severity, activity or associated MetS.

Serum fatty acid binding protein 4 levels are associated with abdominal aortic calcification in peritoneal dialysis patients

Background Fatty acid binding protein 4 (FABP4) is an adipokine that was mainly derived from adipocytes and macrophages. Vascular calcification (VC) is highly prevalent in peritoneal dialysis (PD) patients and could predict their cardiovascular mortality. The pathogenesis of VC is complex, and adipokines may play an important role in it. This study aimed to examine the relationship between serum FABP4 and VC in PD patients. Methods Serum FABP4 was measured by enzyme-linked immunosorbent assay. According to the median value of serum FABP4, the participants were divided into the low FABP4 group and the high FABP4 group. Lateral plain X-ray films of abdomen were used to evaluate the abdominal aortic calcification (AAC) score. The participants were divided into the high AAC score group (AAC score ≥4, indicating moderate or heavy VC) and the low AAC score group (AAC score <4, indicating no or mild VC). Results 116 PD patients were involved in the study. The AAC score and the proportion of patients with an AAC score ≥4 of the high FABP4 group were significantly higher than those of the low FABP4 group. Serum FABP4 of the high AAC score group was significantly higher than that of the low AAC score group [164.5 (138.4, 362.8) ng/mL versus 144.7 (123.8, 170.1) ng/mL, p = 0.002]. Serum FABP4 was positively associated with the AAC score according to the multivariate linear regression analysis. In the multivariate logistic regression analysis, serum FABP4 was the independent influencer of an AAC score ≥4. Conclusions Serum FABP4 is positively associated with the AAC score and is an independent marker of AAC in PD patients.

The adipokine fatty-acid binding protein 4 and cardiac remodeling

BackgroundPrevious publications about the association between fatty-acid binding protein 4 (FABP4) and cardiac remodeling have reported different, both beneficial and harmful, associations. Aim of the present investigation was to evaluate the association of FABP4 with parameters of myocardial remodeling defined by cardiac magnetic resonance imaging (CMR).MethodsWe investigated plasma FABP4 levels in 331 patients (71% men, mean age 63±13 years) with preserved left ventricular ejection fraction (LVEF ≥ 55%) who underwent a CMR examination. We used linear cox regression to investigate associations between FABP4 and left ventricular end-diastolic diameter (LVEDD), right ventricular end-diastolic diameter (RVEDD), relative wall thickness (RWT), left ventricular mass index (LVMI), and LVEF (unadjusted and adjusted for age, sex, body mass index, cardiac biomarkers, and comorbidities).ResultsFABP4 levels were associated with lower LVMI and higher NT-proBNP levels in an adjusted model. The inverse association between FABP4 and LVMI was more pronounced in lower FABP4 levels, whereas the positive association between FABP4 and NT-proBNP was more pronounced in relatively high NT-proBNP levels.ConclusionsPossible beneficial and harmful associations between FABP4 and left ventricular size have been reported. Our results suggest a beneficial association with LVMI (more pronounced in lower FABP4 levels) but a harmful association with NT-proBNP (more pronounced in higher FABP4 levels). Therefore, our results might indicate a potential dose-dependent association of FABP4, but this observation needs further investigation in larger study samples.

The influence of equine body weight gain on inflammatory cytokine expressions of adipose tissue in response to endotoxin challenge

BackgroundHuman obesity is linked with systemic inflammation. However, it is still controversial if equines produce more inflammatory cytokines with increasing body weight and if the production of those show breed type specific patterns. The main objective of this study was to determine if diet induced obesity is associated with increased inflammatory signatures in adipose tissue of equines and if a breed predisposition exists between ponies and horses. Additionally, we aimed to identify adipose tissue depot differences in inflammatory cytokine expression. Nineteen healthy, non-overweight and metabolically healthy equines received a hypercaloric diet for 2 years. Body weight, body condition score and cresty neck score were assessed weekly throughout the study. At three time points, insulin sensitivity was determined by a combined glucose-insulin test. Adipose tissue samples were collected from two intra-abdominal and two subcutaneous depots under general anesthesia at each time point after an endotoxin trigger. In the adipose tissue samples levels of CD68 mRNA (a marker of macrophage infiltration) and pro-inflammatory cytokine mRNA (IL-1β, IL-6 and TNFα) were analyzed with RT-qPCR. As markers of lipid metabolism mRNA levels of lipoprotein lipase (LPL) and fatty acid binding protein 4 (FABP4) were determined with RT-qPCR.ResultsCD68 mRNA levels increased with body weight gain in several adipose tissue (AT) depots (Wilcoxon signed rank test with Bonferroni correction; retroperitoneal AT horses: P = 0.023, mesocolonial AT horses: P = 0.023, subcutaneous tail head AT ponies: P = 0.015). In both abdominal depots CD68 mRNA levels were higher than in subcutaneous adipose tissue depots (Kruskal–Wallis-ANOVA with Bonferroni correction: P < 0.05). No breed related differences were found. Pro-inflammatory cytokine mRNA IL-1β, IL-6 and TNFα levels were higher in subcutaneous depots compared to abdominal depots after body weight gain. IL-1β, IL-6 and TNFα mRNA levels of mesocolon adipose tissue were higher in obese horses compared to obese ponies (Mann–Whitney-U test; IL-1β: P = 0.006; IL-6: P = 0.003; TNFα: P = 0.049). In general, horses had higher FABP4 and LPL mRNA levels compared to ponies in neck AT and tail AT at all time points.ConclusionOur findings suggest an increased invasion of macrophages in intra-abdominal adipose tissue with increasing body weight gain in equines in combination with a low dose endotoxin stimulus. This might predispose equines to obesity related comorbidities. In obese horses mesocolon adipose tissue showed higher inflammatory cytokine expression compared to obese ponies. Additionally, subcutaneous adipose tissue expressed more pro-inflammatory cytokines compared to intra-abdominal adipose tissue. Horses had higher FABP4 and LPL mRNA levels in selected AT depots which may indicate a higher fat storage capacity than in ponies. The differences in lipid storage might be associated with a higher susceptibility to obesity-related comorbidities in ponies in comparison to horses.

Expression and correlation of Chemerin and FABP4 in peripheral blood of gestational diabetes mellitus patients

Expression and correlation of Chemerin and fatty acid-binding protein 4 (FABP4) in peripheral blood of gestational diabetes mellitus (GDM) patients were investigated. Sixty patients with GDM from March 2018 to March 2019 in the People's Hospital of Zhangqiu Area were selected as the study group (SG) and another 50 healthy pregnant women corresponding to their age and pregnancy were selected as the control group (CG). Enzyme linked immunosorbent assay (ELISA) was used to detect the expression of Chemerin and FABP4 in serum. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of Chemerin and FABP4 in peripheral blood for GDM patients. Pearson's correlation coefficient was used to analyze the correlation between Chemerin and FABP4 and the correlation between Chemerin and inflammatory factors such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Expression of Chemerin and FABP4 in peripheral blood of GDM patients were significantly higher than those in CG. The AUC of GDM patients diagnosed with Chemerin and FABP4 in peripheral blood was 0.820 and 0.814, while the AUC of GDM patients diagnosed with Chemerin combined with FABP4 in peripheral blood was 0.904. Expression of inflammatory factors IL-6 and TNF-α in the SG were significantly higher than those in the CG. Chemerin in the SG was positively correlated with FABP4 and positively correlated with inflammatory factors IL-6 and TNF-α. Patients with advanced age (≥35 years), family history of diabetes, hyperlipidemia, high pre-pregnancy BMI, high fasting blood glucose, high Chemerin and high FABP4 expression have high risk of GDM. In conclusion, Chemerin and FABP4 were upregulated in the peripheral blood of GDM patients. There was a positive correlation between the two and a positive correlation with the inflammatory factors IL-6 and TNF-α.

FABP4 as a biomarker for knee osteoarthritis.

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

Fatty acid binding protein 4 enhances prostate cancer progression by upregulating matrix metalloproteinases and stromal cell cytokine production.

Fatty acid binding protein 4 (FABP4) is an abundant protein in adipocytes, and its production is influenced by high-fat diet (HFD) or obesity. The prostate stromal microenvironment induces proinflammatory cytokine production, which is key for the development and progression of prostate cancer (PCa). Here, we show that high FABP4 expression and its secretion by PCa cells directly stimulated PCa cell invasiveness by upregulating matrix metalloproteinases through phosphatidylinositol 3-kinase and mitogen-activated protein kinase signaling pathways. In addition, prostate stromal cells augmented PCa cell invasiveness by secreting interleukin-8 and -6 in response to FABP4. This was abrogated by the FABP4 specific inhibitor, BMS309403. Furthermore, a mouse xenograft experiment showed HFD enhanced PCa metastasis and invasiveness by the upregulation of FABP4 and interleukin-8. Clinically, the serum level of FABP4 was significantly associated with an aggressive type of PCa rather than obesity. Taken together, FABP4 may enhance PCa progression and invasiveness by upregulating matrix metalloproteinases and cytokine production in the PCa stromal microenvironment, especially under HFD or obesity.

New insight into determining indicators of metabolic status in women: Expression of PPARγ and FABP4 in PBMCs

ABSTRACTAdiposity and its metabolic disturbances could be regulated by adipocyte-specific peroxisome proliferator-activated receptor gamma and fatty acid-binding protein4. Although these two proteins are mainly expressed in adipose tissues, they can also be expressed in peripheral blood mononuclear cells, which could be useful for predicting body composition and blood parameters. Thus, this cross-sectional study was performed during January 2013–January 2014 with 229 women (age range, 22–52 years) who were classified as obese or nonobese. Serum glucose, insulin, lipids, and body composition were measured in the fasting state. Peripheral blood mononuclear cells were isolated to extract ribonucleic acid (RNA) and to determine gene expression by real time polymerase chain reaction (PCR). All serum parameters and components of body composition were significantly higher in obese than in nonobese women. Gene expression analysis showed that serum levels of glucose and lipids, except high-density lipoprotein (HDL), were higher in the group that expressed high fatty acid-binding protein4. Increased expression of the peroxisome proliferator-activated receptor gamma was associated with a significant reduction of blood sugar and increased HDL and other lipids and visceral fat. Therefore, it seems that the level of expression of these genes in peripheral blood mononuclear cells may indicate metabolic status.

Radiofluorinated probe for PET imaging of fatty acid binding protein 4 in cancer

IntroductionCancer-associated adipocytes metabolically interact with adjacent cancer cells to promote tumor proliferation and metastasis. Fatty acid binding protein 4 (FABP4) participates in this interaction, and is gathering attention as a therapeutic and diagnostic target. Positron emission tomography (PET) is a useful diagnostic method that enables noninvasive in vivo quantitative imaging of biofunctional molecules with probes labeled with positron-emitting radioisotopes. Here a novel 18F labeled probe for PET FABP4 imaging developed through dedicated drug design from a radioiodinated probe we recently reported is evaluated in vitro and in vivo. MethodsWe designed the [18F]-labeled FTAP1 and FTAP3 probe, composed of a single or triple oxyethylene linker and a triazolopyrimidine scaffold derived from an FABP4 inhibitor. FABP4 binding affinities for chemically synthesized FTAP1 and FTAP3 were measured using FABP4 and 8-anilino-1-naphthalene sulfonic acid. Cell membrane permeability was measured using a commercially available plate assay system. After radiosynthesis, [18F]FTAP1 affinity and selectivity were evaluated using immobilized FABP3, FABP4, and FABP5. Cell uptake was investigated using differentiated adipocytes expressing FABP4 with inhibitor treatment. Following biodistribution studies in C6 glioblastoma-bearing mice, ex vivo autoradiography and immunohistochemistry were performed using thin sliced tumor sections. PET/CT imaging was then performed on C6 tumor bearing mice. ResultsFTAP1 showed high FABP4 affinity (Ki=68±8.9 nM) and adequate cell permeability. [18F]FTAP1 with ≥98% radiochemical purity was shown to selectively bind to FABP4 (16.3- and 9.3-fold higher than for FABP3 and FABP5, respectively). [18F]FTAP1 was taken up by FABP4 expressing cells, and this uptake could be blocked by an inhibitor, indicating very low non-specific cell binding. [18F]FTAP1 showed high tumor accumulation, which demonstrates its potential use for in vivo tumor PET imaging, and the intratumoral radioactivity distribution corresponded to the FABP4 expression profile. Conclusion[18F]FTAP1 is a promising PET probe to target FABP4.

Abstract 18168: Plasma Free Fatty Acids, Fatty Acid-Binding Protein 4, and Mortality in Older Adults in the Cardiovascular Health Study

Background: Plasma free fatty acids (FFA) are important in energy homeostasis and fatty acid-binding protein 4 (FABP4) is a key cytoplasmic chaperone of fatty acids. While both FFA and FABP4 have been associated with cardiovascular risk factors and cardiovascular events, limited and inconsistent data are available on the relation of these biomarkers with cardiovascular and total mortality. Methods and Results: We studied 4,707 participants with plasma FFA and FABP4 measured at baseline (1992-1993) in the Cardiovascular Health Study. The mean age of the participants was 75 (range 64-98) and 58.3% were women. Over a median follow-up of 11.8 years, 3,555 of the participants died. Cox proportional hazard models were used to estimate hazard ratios (HR) for mortality. After adjustment for age, sex, race, clinic, education, body-mass index, cystatin c, albumin, physical activity, alcohol intake, smoking, hormone replacement therapy in women, self-reported health status, systolic blood pressure, LDL cholesterol, HDL cholesterol, hypertensive medication, and lipid-lowering medication, FFA (HR: 1.14, 95% CI 1.09-1.18 per SD [0.2 mEq/L] higher FFA) but not FABP4 (HR: 1.04 (95% CI: 0.98-1.09 per SD [18.9 ng/mL] higher FABP4) levels were associated with total mortality. In a cause-specific mortality analysis, higher concentrations of FFA were associated with a greater risk of death due to cardiovascular and certain non-cardiovascular causes (Table 1). Conclusion: In a cohort of community-dwelling older individuals, elevated plasma concentrations of FFA (but not FABP4) were associated with cardiovascular and non-cardiovascular mortality.

Fatty acid binding protein 4 predicts left ventricular mass and longitudinal function in overweight and obese women

ObjectiveTo explore whether increased adipocyte-derived serum fatty acid binding protein 4 (FABP4) predisposes to cardiac remodelling and left ventricular dysfunction in human obesity.DesignCross-sectional investigation.SettingAcademic clinical research centre.Patients108 overweight and obese...

A study of fatty acid binding protein 4 in HIV-1 infection and in combination antiretroviral therapy-related metabolic disturbances and lipodystrophy

The aim of the study was to determine circulating levels of fatty acid binding protein 4 (FABP-4) in a cohort of HIV-1-infected patients treated with combination antiretroviral therapy (cART) and to investigate the relationships between FABP-4 levels and insulin resistance, dyslipidaemia, lipodystrophy and levels of proinflammatory adipocytokines in these patients. A total of 282 HIV-1-infected patients treated with stable cART for at least 1 year (132 with lipodystrophy and 150 without) and 185 uninfected controls (UCs) were included in the study. Anthropometric parameters were determined. Plasma levels of FABP-4, soluble tumour necrosis factor receptors 1 and 2 (sTNF-R1 and sTNF-R2), interleukin-18 (IL-18), IL-6, adiponectin and leptin were also analysed. Insulin resistance was determined using the homeostasis model assessment of insulin resistance (HOMA-IR). Subcutaneous adipose tissue mRNA expression of proinflammatory cytokines was assessed in 38 patients (25 with lipodystrophy and 13 without) by real-time polymerase chain reaction (PCR). The plasma FABP-4 concentration was significantly higher in patients with lipodystrophy than in those without (P=0.012). FABP-4 concentration was positively correlated with body mass index (BMI), HOMA-IR, and the concentrations of insulin, total cholesterol, triglycerides, sTNF-R1, leptin and IL-18, but showed a negative correlation with high-density lipoprotein (HDL) cholesterol and adiponectin concentrations. After adjusting for age, sex and BMI, the odds ratio (OR) for risk of lipodystrophy was found to be significantly increased for those with the highest levels of FABP-4 [OR 0.838, 95% confidence interval (CI) 0.435-1.616 for medium FABP-4 vs. OR 2.281, 95% CI 1.163-4.475 for high FABP-4]. In a stepwise regression model, FABP-4 was independently associated with HOMA-IR after controlling for clinical and inflammatory parameters (P=0.004). Moreover, a positive relationship was observed in patients with lipodystrophy between subcutaneous adipose tissue CD68 expression and FABP-4 plasma levels (r=0.525; P=0.031). cART-treated HIV-1-infected patients with lipodystrophy have a systemic overproduction of FABP-4, which is closely linked to insulin resistance and inflammatory markers in subcutaneous adipose tissue.

Plasma fatty acid binding protein 4 is associated with atherogenic dyslipidemia in diabetes

The aim of this study was to evaluate the impact of adipocyte fatty acid binding protein 4 (FABP4) on the lipid profile in type 2 diabetic subjects. Plasma levels of FABP4 and adiponectin and an extensive lipid profile were analyzed in 169 type 2 diabetic subjects and 105 controls. Type 2 diabetic subjects were categorized according the presence of atherogenic dyslipidemia. Univariate statistical analyses, partial correlation tests, and binary logistic regression models were applied. In type 2 diabetic subjects, FABP4 was positively correlated with plasma triglycerides (P = 0.007), apolipoprotein C-III (apoC-III) (P = 0.009), and all the components of triglyceride-rich lipoproteins, including VLDL triglycerides (P = 0.002), VLDL-cholesterol (P = 0.001), and VLDL apoB (P = 0.001). FABP4 was inversely correlated with apoA-I (P = 0.038), HDL-cholesterol (P = 0.002), and HDL apoA-I (P = 0.010) in type 2 diabetic subjects. These correlations are not significantly affected by age, gender, body mass index, adiponectin, insulin, or any pharmacological treatment. The associations are even stronger when the FABP4/adiponectin ratio is considered. None of these associations were observed in controls. High FABP4 and low adiponectin levels are independent predictors of atherogenic dyslipidemia. In conclusion, FABP4 plasma concentrations hold strong potential for development as a clinical biomarker for atherogenic dyslipidemia, independent of obesity and insulin resistance, in type 2 diabetic subjects.

Plasma Fatty Acid-Binding Protein 4 Increases with Renal Dysfunction in Type 2 Diabetic Patients without Microalbuminuria

Fatty acid-binding protein 4 (FABP4) has been linked to metabolic syndrome development, diabetes, and arteriosclerosis, but the role of FABP4 in target organ damage has not been assessed. We evaluated whether plasma FABP4 is associated with renal dysfunction in type 2 diabetic patients. In 263 individuals (161 type 2 diabetic patients and 102 healthy nondiabetic controls), we analyzed the correlation between FABP4 and creatinine or glomerular filtration index (MDRD-GFR) regarding the presence or absence of microalbuminuria. Patients with severe chronic kidney disease (MDRD-GFR <30 mL/min/1.73 m(2)) or albuminuria were not included. FABP4 concentrations were higher in diabetic patients with MDRD-GFR <60 mL/min/1.73 m(2) (P <0.001). We observed a significant, direct correlation between FABP4 and creatinine (r = 0.446, P <0.001) and an inverse correlation between FABP4 and MDRD-GFR (r = -0.511, P <0.001) in type 2 diabetic patients, but not in nondiabetic individuals. These correlations were sustained when only those patients without microalbuminuria were analyzed (r = 0.414, P <0.001 and r = -0.510, P <0.001, respectively). Type 2 diabetic patients with FABP4 in the highest tertile compared with those in the lower tertiles had increased adjusted odds ratios for moderate renal dysfunction [7.5 (95%CI 1.8-30.7), P = 0.005 and 15.3 (3.1-76.4), P = 0.001; respectively], independent of microalbuminuria. High FABP4 plasma concentrations are associated with high plasma creatinine and low MDRD-GFR in patients with type 2 diabetes even in the absence of microalbuminuria or clinically relevant alterations of creatinine and MDRD-GFR values. FABP4 concentrations should be taken into consideration as an early marker of kidney damage in patients with type 2 diabetes.