RESUMO
BACKGROUND: Adipose tissue is significantly involved in inflammatory bowel disease (IBD). Vitamin D can affect both adipogenesis and inflammation. The aim of this study was to compare the production of selected adipokines, potentially involved in the pathogenesis of IBD - adiponectin, resistin, retinol binding protein 4 (RBP-4), adipocyte fatty acid binding protein and nesfatin-1 in children with IBD according to the presence of 25-hydroxyvitamin D (25(OH)D) deficiency. METHODS: The study was conducted as a case-control study in pediatric patients with IBD and healthy children of the same sex and age. In addition to adipokines and 25(OH)D, anthropometric parameters, markers of inflammation and disease activity were assessed in all participants. RESULTS: Children with IBD had significantly higher resistin levels regardless of 25(OH)D levels. IBD patients with 25(OH)D deficiency only had significantly lower RBP-4 compared to healthy controls and also compared to IBD patients without 25(OH)D deficiency. No other significant differences in adipokines were found in children with IBD with or without 25(OH)D deficiency. 25(OH)D levels in IBD patients corelated with RBP-4 only, and did not correlate with other adipokines. CONCLUSIONS: Whether the lower RBP-4 levels in the 25(OH)D-deficient group of IBD patients directly reflect vitamin D deficiency remains uncertain. The production of other adipokines does not appear to be directly related to vitamin D deficiency.
Assuntos
Adipocinas , Deficiência de Vitamina D , Vitamina D , Humanos , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/sangue , Masculino , Feminino , Criança , Estudos de Casos e Controles , Adipocinas/sangue , Adolescente , Vitamina D/sangue , Vitamina D/análogos & derivados , Proteínas Plasmáticas de Ligação ao Retinol/metabolismo , Proteínas Plasmáticas de Ligação ao Retinol/análise , Resistina/sangue , Nucleobindinas/sangue , Adiponectina/sangue , Adiponectina/deficiência , Proteínas de Ligação ao Cálcio/sangue , Proteínas de Ligação a Ácido Graxo/sangue , Proteínas de Ligação a DNA/sangue , Biomarcadores/sangue , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/complicaçõesRESUMO
BACKGROUND: Adipocyte fatty acid-binding protein (FABP4) is an adipokine that plays an important role in development of cardiovascular and metabolic diseases. The aim of this study was to assess the 3-month prognostic value of serum levels of FABP4 in Chinese patients with aneurysmal subarachnoid hemorrhage (aSAH) on hospital admission. METHODS: This was a prospective observational study from a stroke treatment center in Zhengzhou, China. From October 2016 to May 2018, patients with aSAH who were hospitalized within 24 h were included. In addition, 202 age- and gender-matched healthy volunteers were assigned to the healthy control group. At admission, serum levels of FABP4 were measured, and patients' characteristics, Hunt-Hess grade, and modified Fisher grade evaluated. At 3-month follow-up, functional outcome (Glasgow Outcome Scale score; dichotomized as poor [score 1-3] or good [score 4-5]) and all-cause mortality were recorded. Univariate and multivariate logistic regression models were used to investigate the association of FABP4 with the two endpoints. RESULTS: A total of 418 patients with aSAH were included in this study. The median age was 58 years (interquartile range, 49-66 years), and 57.9% were women. FABP4 serum levels were related to Hunt-Hess score (r[Spearman] = 0.381; P < 0.001). Patients with a poor outcome and non-survivors had significantly increased serum FABP4 levels on admission (P < 0.001 for all). In multivariate logistic regression analysis, FABP4 was an independent predictor of poor outcome and mortality, with increased risks of 7% (odds ratios 1.07, 95% confidence interval [CI] 1.02-1.13; P = 0.001) and 5% (odds ratio 1.05, 95% CI, 1.01-1.12; P = 0.003), respectively. Receiver operating characteristics to predict functional outcome and mortality were significantly different between conventional risk factors (difference area under the curve 0.024, 95% CI 0.018-0.032) and FABP4 plus conventional risk factors (area under the curve 0.015, 95%CI 0.011-0.020). After FABP4 was added to the existing risk factors, mortality was better reclassified and was associated with the net reclassification improvement statistic (P = 0.009), while poor outcome was better reclassified and associated with both the integrated discrimination improvement and net reclassification improvement statistics (P < 0.05 for all). CONCLUSIONS: Elevated serum FABP4 levels were related to poor outcome and mortality in a cohort of patients with aSAH.
Assuntos
Pessoas com Deficiência , Proteínas de Ligação a Ácido Graxo/sangue , Hemorragia Subaracnóidea/sangue , Hemorragia Subaracnóidea/epidemiologia , Adipócitos/metabolismo , Idoso , Biomarcadores/sangue , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Hemorragia Subaracnóidea/diagnóstico , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE: The circulating level of adipocyte fatty acid-binding protein (AFABP), a biomarker with prognostic and therapeutic importance in metabolic disorders, has been shown to be elevated in obstructive sleep apnea (OSA). This randomized controlled study aimed to investigate the effect of continuous positive airway pressure (CPAP) treatment for OSA on AFABP levels. METHODS: Consecutive subjects attending sleep study were invited if they were confirmed to have severe OSA and were free of metabolic diseases. Participants were randomized (1:1) into CPAP or observation group for 4 weeks. Demographics, anthropometric data, and circulating biomarkers were checked at baseline and after the 4-week study period. RESULTS: Ninety subjects were randomized. The mean age was 46 ± 9 years old; 82% were male. Their mean body mass index (BMI) was 29 ± 5 kg/m2. By intention-to-treat approach, the CPAP group showed significant reductions in Epworth sleepiness scale and morning systolic blood pressure (- 7.2 mmHg, - 12.7 to - 1.7 mmHg, p = 0.011), but no significant difference in AFABP, adiponectin, C-reactive protein (CRP), and 8-isoprostane levels. In the per-protocol analysis, when only those who were compliant to CPAP were included, a significant reduction in AFABP (- 7.32 ng/ml, - 13.58, - 1.06, p = 0.023) were found in the CPAP-treated group compared with the control group, along with improvements in clinical parameters. Changes in AFABP were independently associated with both systolic blood pressure (ß = 0.289, p = 0.028) and diastolic blood pressure (ß = 0.217, p = 0.030). CONCLUSION: CPAP therapy used regularly over 4 weeks for severe OSA lowered circulating AFABP level, suggesting a potential beneficial effect of OSA treatment on alleviating metabolic risks. TRIAL REGISTRATION: The research protocol was registered at the National Institutes of Health clinical trials registry (NCT01173432).
Assuntos
Pressão Positiva Contínua nas Vias Aéreas/métodos , Proteínas de Ligação a Ácido Graxo/sangue , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/terapia , Sono/fisiologia , Adulto , Biomarcadores/sangue , Pressão Sanguínea/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
BACKGROUNDS: Adiponectin, adipocyte-fatty acid binding protein (A-FABP), and Wnt1 inducible signaling pathway protein-1 (WISP-1) are adipokines closely associated with insulin resistance. The aim of the study was to compare their levels in women with gestational diabetes (GDM), type 2 diabetes mellitus (T2DM) and healthy controls and determine their relation to metabolic parameters. METHODS: Women with GDM, T2DM and healthy women were included in this cross-sectional study. In addition to adipokines, anthropometric, lipid parameters, markers of insulin resistance and glucose control were assessed in all participants. RESULTS: Compared to healthy controls (n = 35) significantly lower levels of adiponectin were detected in women with GDM (n = 50), whereas in women with T2DM (n = 50) higher levels of A-FABP and WISP-1 and lower levels of adiponectin were found. Women with T2DM had also lower levels of adiponectin and higher levels of A-FABP compared to women with GDM. A-FABP and adiponectin were independently associated with levels of triglycerides, HDL-cholesterol and C-peptide insulin resistance index. WISP-1 correlated only with waist circumference. CONCLUSIONS: Adverse adipokines production reflecting dysfunctional fat tissue is less presented in women with GDM than in women with T2DM, but more expressed compared to healthy women.
Assuntos
Adipocinas , Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Resistência à Insulina , Adipocinas/sangue , Adiponectina , Estudos Transversais , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Gestacional/metabolismo , Feminino , Humanos , GravidezRESUMO
AIMS/HYPOTHESIS: Elevated circulating adipocyte fatty acid-binding protein (AFABP) levels have been found to correlate with diabetic nephropathy staging in cross-sectional studies. However, it remains unclear whether these higher serum levels reflect a role of AFABP in the development of diabetic kidney disease (DKD), or simply result from its impaired renal clearance in DKD. Here we investigated prospectively the prognostic importance of serum AFABP level in the development of adverse renal outcomes in a large clinic-based cohort of participants with type 2 diabetes. METHODS: Baseline serum AFABP levels were measured in 5454 Chinese participants from the Hong Kong West Diabetes Registry. The association between circulating AFABP levels and incident adverse renal outcomes-defined as a composite endpoint of a sustained 40% decline in eGFR, end-stage renal disease requiring renal replacement therapy or kidney transplantation, or renal deaths-was evaluated using multivariable Cox regression analysis. RESULTS: Over a median follow-up of 5 years, 754 of the 5454 participants developed incident adverse renal outcomes. Elevated circulating AFABP levels were independently associated with incident adverse renal outcomes (HR 1.43, 95% CI 1.31, 1.57, p < 0.001) after adjustments for conventional risk factors for DKD progression. Importantly, the prognostic role of serum AFABP was independent of the baseline albuminuria status or eGFR levels of the study participants. CONCLUSIONS/INTERPRETATION: Circulating AFABP levels were predictive of incident adverse renal outcomes, even in participants with relatively well-preserved kidney function at baseline, suggesting its potential to be a useful marker for early risk stratification in DKD.
Assuntos
Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/patologia , Proteínas de Ligação a Ácido Graxo/sangue , Adulto , Idoso , Albuminúria/sangue , Albuminúria/patologia , Estudos Transversais , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/patologia , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos ProspectivosRESUMO
BACKGROUND & AIMS: Serum adipocyte fatty acid-binding protein (A-FABP) is closely correlated to metabolic disorders such as obesity and insulin resistance (IR). Non-alcoholic fatty liver disease (NAFLD) is a typical feature of IR in the liver. The aim of this study was to explore the relationship between serum A-FABP levels and NAFLD. METHODS: The study enrolled 728 subjects with normal glucose tolerance from communities. Serum A-FABP levels were measured using a sandwich enzyme-linked immunosorbent assay. The liver fat content was assessed by ultrasonography. The fatty liver index (FLI) was calculated to quantify the degree of liver steatosis. The upper quartile of homoeostasis model assessment-insulin resistance (HOMA-IR) in the total population was defined as IR. Adipose tissue insulin resistance (Adipo-IR) was calculated to evaluate the impaired suppression of lipolysis in IR. RESULTS: Serum A-FABP levels were significantly higher in subjects with NAFLD than in those without (P < 0.01). Moreover, subjects with IR had higher levels of A-FABP than those without (P < 0.01). The proportion of IR or NAFLD and the levels of fasting free fatty acid (FFA) or Adipo-IR displayed an upward trend as A-FABP increased (P for trend < 0.05). After adjusting for gender, age, body fat, metabolic factors and liver enzymes, A-FABP was independently correlated with NAFLD (P < 0.01). A-FABP was a positive determinant of FLI (P = 0.006). CONCLUSIONS: Serum A-FABP levels were significantly elevated in NAFLD patients among a population with normal glucose tolerance. Serum A-FABP levels were independently correlated with NAFLD after adjusting for confounding factors.
Assuntos
Proteínas de Ligação a Ácido Graxo/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , Adulto , Idoso , Povo Asiático , Biomarcadores/sangue , China/epidemiologia , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Resistência à Insulina , Lipólise , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/etnologia , Ultrassonografia , Regulação para CimaRESUMO
1. Adipocyte fatty acid binding protein (A-FABP) plays a key role in fatty acid uptake and intracellular transport. The objective of the present study was to identify and characterise the A-FABP gene in Xupu goose.2. The full-length cDNA of goose A-FABP gene was cloned from the liver tissue using reverse transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE). The distribution of the goose A-FABP in different tissues was determined by quantitative real-time PCR (qRT-PCR).3. The results showed that the full-length cDNA sequence of goose A-FABP was 657 bp, containing a 5'-UTR of 52 bp, a 3'-UTR of 206 bp and an open reading frame (ORF) of 399 bp, which encoded a polypeptide of 132 amino acids (AA).4. The AA sequence of goose A-FABP showed 76.52%, 75.00%, 93.18% and 99.24% identities with previously described homologues from humans (Homo sapiens), mouse (Mus musculus), chicken (Gallus gallus), and duck (Anas platyrhynchos), respectively, and phylogenetic analysis revealed a close relationship among them. The transcript of Xupu goose A-FABP was ubiquitously expressed in all tested tissues, and showed a high-level expression in abdominal fat, sebum and liver.5. A significant positive correlation was identified between A-FABP mRNA abundance in the three adipose tissues and liver weight, ratio of liver to body weight, TG content, and VLDL concentration in the plasma of Xupu goose. A significant negative correlation was observed between the mRNA level of A-FABP and HDL concentration in the plasma of Xupu goose.6. These findings provide a foundation for further research on the function and mechanism of A-FABP in the fat deposition process.
Assuntos
DNA Complementar/química , Proteínas de Ligação a Ácido Graxo/genética , Gansos/genética , Gordura Abdominal/química , Adipócitos/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , China , Clonagem Molecular , DNA Complementar/biossíntese , Proteínas de Ligação a Ácido Graxo/química , Proteínas de Ligação a Ácido Graxo/metabolismo , Gansos/classificação , Gansos/metabolismo , Perfilação da Expressão Gênica/veterinária , Fígado/química , Masculino , Filogenia , RNA Mensageiro/análise , RNA Mensageiro/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa/veterinária , Sebo/química , Alinhamento de Sequência/veterináriaRESUMO
BACKGROUND: Non-muscle invasive bladder cancers (NMIBC: pTa, pT1) are characterised by a high risk of recurrence and/or progression. Identification of prognostic markers is needed to improve both diagnosis and management of the disease. The aim of this study was to analyse the expression of A-FABP (adipocyte-fatty acid binding protein) and to evaluate its prognostic value in bladder cancer with a long term clinical follow-up. METHODS: A-FABP expression was investigated by immunohistochemistry in 236 tumours (114 pTa, 61 pT1, 61 pT2-4). Immunostaining was classified as negative (absent or weak immunostaining and moderate or strong staining on ≤10% of cells) or positive (moderate or strong staining on > 10% of cells). Event-free survival (EFS) and overall survival (OS) were determined with a 87.3 months median follow-up in the overall cohort. Recurrence-free survival (RFS) and progression-free survival (PFS) were established in NMIBC. RESULTS: Loss of A-FABP was associated with higher mean age, high stage/grade, and the presence of metastatic lymph nodes. It was correlated with shorter median EFS (17.5 vs 62.5 months; p = 0.001) and mean OS (76.7 vs 154.2 months; p = 0.009) and with higher risk of progression in the pTa/pT1 subgroup (HR, 0.36; 95% CI, 0.13-0.96; p = 0.041) and importantly in the pTa tumours (HR, 0.34; 95% CI, 0.10-0.97; p = 0.045). CONCLUSION: These results demonstrated that loss of A-FABP expression following a long follow-up was predictive of pTa and pTa/pT1 progression. Immunohistochemistry on diagnostic biopsy is easy to use and could be of value to help clinicians to propose appropriate treatment for these tumours.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células de Transição/patologia , Proteínas de Ligação a Ácido Graxo/biossíntese , Neoplasias da Bexiga Urinária/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/metabolismo , Carcinoma de Células de Transição/mortalidade , Progressão da Doença , Regulação para Baixo , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/mortalidadeRESUMO
Background: Adipocyte fatty acid-binding protein (A-FABP) is a cardiometabolic predictor of cardiovascular (CV) disease in humans. We evaluated the association between serum A-FABP levels and future CV events in patients with coronary artery disease (CAD). Methods: A total of 106 CAD patients were enrolled in this study between January and December 2012 and were followed-up until June 30, 2017. The primary endpoint was the incidence of major adverse CV events. Results: During a median follow-up period of 53 months, 44 CV events occurred. Patients with CV events presented higher systolic blood pressure (p = 0.020), total serum cholesterol (p = 0.047), and serum A-FABP levels (p < 0.001) compared with patients without CV events. Kaplan-Meier analysis showed that the cumulative incidence of CV events in the high A-FABP group (median A-FABP concentration of >17.63 ng/mL) was higher than that in the low A-FABP group (log-rank p < 0.001). Multivariate Cox analysis showed that triglycerides (hazard ratio (HR): 1.008, 95% confidence interval (CI): 1.001-1.016, p = 0.026) and serum A-FABP levels (HR: 1.027, 95% CI: 1.009-1.047, p = 0.004) were independently associated with CV events. Conclusion: Serum A-FABP level is a biomarker for future CV events in patients with CAD. Further prospective studies are needed to confirm the mechanisms underlying this association.
Assuntos
Adipócitos , Doença da Artéria Coronariana/sangue , Proteínas de Ligação a Ácido Graxo/sangue , Idoso , Biomarcadores/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , TaiwanRESUMO
BACKGROUND: Arterial stiffness is an established marker of cardiovascular risk and an independent predictor of cardiovascular disease (CVD) events and mortality in kidney transplant (KT) patients. Adipocyte fatty acid-binding protein (A-FABP), a novel adipokine, is positively associated with atherosclerosis. The present study evaluated the relationship between fasting circulating A-FABP and peripheral arterial stiffness using the cardio-ankle vascular index (CAVI) in KT patients. METHODS: Fasting blood samples were collected from 74 KT patients, and serum A-FABP levels were measured using an enzyme immunoassay. CAVI was calculated using a waveform device (CAVI-VaSera VS-1000). The cutoff values for high and low levels of arterial stiffness were defined by the CAVI values of ≥9 and <9, respectively. RESULTS: Thirty-four patients (45.9%) were classified into the high arterial stiffness group. Compared with the low arterial stiffness group, the high arterial stiffness group had higher values for age (p = 0.015), systolic blood pressure (p < 0.001), pulse pressure (p < 0.001), duration of kidney transplantation (p = 0.005), serum total cholesterol and triglyceride levels (p = 0.033 and 0.047, respectively), glomerular filtration rate (p = 0.019), fasting glucose levels (p = 0.012), and serum A-FABP levels (p < 0.001). Multivariate forward stepwise linear regression analysis showed that age (p = 0.004), systolic blood pressure (p = 0.001), and serum A-FABP levels (p = 0.003) were independent predictors of CAVI value in KT patients. CONCLUSION: Serum fasting A-FABP level is positively associated with peripheral arterial stiffness in KT patients.
Assuntos
Índice Tornozelo-Braço , Proteínas de Ligação a Ácido Graxo/sangue , Transplante de Rim , Rigidez Vascular , Adulto , Idoso , Envelhecimento , Glicemia/análise , Pressão Sanguínea , Colesterol/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Análise de Onda de Pulso , Triglicerídeos/sangueRESUMO
AIM: We aimed to explore the relation between the level of adipocyte fatty-acid binding protein (A-FABP) in the gestational period and related indices of glucolipid metabolism, and the possible mechanisms of occurrence and development of pre-eclampsia. METHODS: Seventy-six pre-eclampsia patients were enrolled and divided into the mild pre-eclampsia (n = 42) and severe pre-eclampsia (n = 34) groups. Forty-eight healthy pregnant women were selected as a control group. The indices of all participants were examined, including serum A-FABP, fasting insulin (FINS), fasting blood glucose, total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), and homeostatic model assessment insulin resistance (HOMA-IR) index was calculated. After the delivery of the placenta, the level of A-FABP in the placenta was detected by immunochemistry. Then, the correlation between serum A-FABP and indices of glucolipid metabolism and placental A-FABP were analyzed. RESULTS: Serum A-FABP, FINS, TG, TC, HOMA-IR, and placental A-FABP were significantly higher in pre-eclampsia patients and the level of HDL was obviously lower than in the control group. Serum A-FABP was positively correlated with FINS, TG, TC, and HOMA-IR, and placental A-FABP was negatively correlated with HDL in pre-eclampsia patients. In the control group, serum A-FABP was positively correlated only with TG, and uncorrelated with the other indices (P > 0.05). CONCLUSION: The level of A-FABP was correlated with insulin resistance and indices of glucolipid metabolism in pre-eclampsia patients. High-levels of A-FABP might increase insulin resistance by causing glucose and lipid metabolism disorders and ultimately inducing the occurrence and development of pre-eclampsia.
Assuntos
Glicemia/análise , HDL-Colesterol/sangue , Proteínas de Ligação a Ácido Graxo/metabolismo , Resistência à Insulina , Insulina/sangue , Lipoproteínas HDL/sangue , Pré-Eclâmpsia/sangue , Triglicerídeos/sangue , Adulto , Proteínas de Ligação a Ácido Graxo/sangue , Feminino , Humanos , Recém-Nascido , GravidezRESUMO
OBJECTIVE: Lipodystrophy (LD) syndromes are associated with diabetes mellitus, hypertriglyceridemia, and coronary artery disease. One pathogenetic factor of LD is dysregulation of several adipokines. However, the insulin resistance- and dyslipidemia-promoting adipokines adipocyte (AFABP) and epidermal (EFABP) fatty acid-binding protein have not been investigated in non-HIV-associated LD so far. MATERIAL AND METHODS: We performed a cross-sectional analysis of AFABP and EFABP serum concentrations in 37 LD patients and 37 age-, gender-, and body mass index-matched healthy controls. Moreover, AFABP and EFABP were correlated to clinical and biochemical parameters of inflammation, glucose control, and lipid metabolism. RESULTS: There was no significant difference in median circulating AFABP and EFABP levels between LD patients (21.7µg/l and 7.5µg/l, respectively) and healthy controls (24.5µg/l and 8.6µg/l, respectively). Neither AFABP nor EFABP were related to markers of impaired glucose control or lipid metabolism. Multiple linear regression analysis showed a positive and independent association of AFABP with gender, serum leptin levels, and body mass index. CONCLUSIONS: Circulating levels of AFABP and EFABP are not decreased in LD despite adipose tissue loss in contrast to other adipokines including leptin and adiponectin.
Assuntos
Proteínas de Ligação a Ácido Graxo/sangue , Lipodistrofia/sangue , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Clinical evidence shows that circulating levels of adipocyte fatty-acid-binding protein (A-FABP) are elevated in patients with diabetes and closely associated with ischaemic heart disease. Patients with diabetes are more susceptible to myocardial ischaemia/reperfusion (MI/R) injury. The experiments in the present study investigated the role of A-FABP in MI/R injury with or without diabetes. Non-diabetic and diabetic (streptozotocin-induced) A-FABP knockout and wild-type mice were subjected to MI/R or sham intervention. After MI/R, A-FABP knockout mice exhibited reductions in myocardial infarct size, apoptotic index, oxidative and nitrative stress, and inflammation. These reductions were accompanied by an improved left ventricular function compared with the relative controls under non-diabetic or diabetic conditions. After diabetes induction, A-FABP knockout mice exhibited a preserved cardiac function compared with that in wild-type mice. Endothelial cells, but not cardiomyocytes, were identified as the most likely source of cardiac A-FABP. Cardiac and circulating A-FABP levels were significantly increased in mice with diabetes or MI/R. Diabetes-induced superoxide anion production was significantly elevated in wild-type mice, but diminished in A-FABP knockout mice, and this elevation contributed to the exaggeration of MI/R-induced cardiac injury. Phosphorylation of endothelial nitric oxide synthase (eNOS) and production of nitric oxide (NO) were enhanced in both diabetic and non-diabetic A-FABP knockout mice after MI/R injury, but diminished in wild-type mice. The beneficial effects of A-FABP deficiency on MI/R injury were abolished by the NOS inhibitor N(G)-nitro-L-arginine methyl ester. Thus, A-FABP deficiency protects mice against MI/R-induced and/or diabetes-induced cardiac injury at least partially through activation of the eNOS/NO pathway and reduction in superoxide anion production.
Assuntos
Diabetes Mellitus/metabolismo , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/fisiologia , Isquemia Miocárdica/terapia , Miocárdio/patologia , Animais , Ânions , Apoptose , Pressão Sanguínea , Endotélio Vascular/metabolismo , Imuno-Histoquímica , Inflamação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microscopia de Fluorescência , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Estresse Oxidativo , Traumatismo por Reperfusão , Superóxidos/metabolismoRESUMO
OBJECTIVE: Irisin has recently been introduced as a novel an exercise-inducible myokine which improves glucose metabolism in mice. However, regulation of circulating irisin in gestational diabetes mellitus (GDM) and in the peripartal period has not been assessed so far. METHODS: Circulating irisin was quantified in 74 GDM patients and in 74 healthy, pregnant, gestational age-matched controls. In a subset of these patients (44 GDM, 41 controls), postpartum follow-up data were also available. In a second study population of 40 healthy women with singleton pregnancies undergoing elective Cesarean section, irisin was assessed in maternal serum before and within 24h after delivery, as well as in umbilical cord blood and in placental tissue. RESULTS: In the first study population, median [interquartile range] irisin levels were significantly higher in GDM patients as compared to controls after delivery (previous GDM: 446.3 [146.9]µg/l; controls: 378.0 [111.4]µg/l) but not during pregnancy (GDM: 482.1 [132.1]µg/l; controls: 466.6 [178.0]µg/l). Interestingly, fasting insulin (FI) was independently and positively associated with serum irisin in multivariate analysis during pregnancy. In agreement with these findings, relative changes (ratio) of FI independently and positively predicted relative changes of irisin (ratio) in the second study population. CONCLUSIONS: The myokine irisin is independently associated with FI in pregnancy. The physiological significance of these findings needs to be assessed in future experiments.
Assuntos
Parto Obstétrico , Diabetes Gestacional/sangue , Fibronectinas/sangue , Adulto , Animais , Estudos de Casos e Controles , Jejum/sangue , Feminino , Humanos , Insulina/sangue , Camundongos , Análise Multivariada , Período Periparto/sangue , Período Pós-Parto/sangue , Gravidez , Análise de RegressãoRESUMO
Obesity is considered to be a chronic inflammatory state in which the dysfunction of adipose tissue plays a central role. The adipokines, which are cytokines secreted by adipose tissue, are key links between obesity and related diseases such as metabolic syndrome and atherosclerosis. LCN2 and A-FABP, both of which are major adipokines predominantly produced in adipose tissue, have recently been shown to be pivotal modulators of vascular function. However, different adipokines modulate the development of atherosclerosis in distinctive manners, which are partly attributable to their unique regulatory mechanisms and functions. This review highlights recent advances in the understanding of the role of two adipokines in mediating chronic inflammation and the pathogenesis of atherosclerosis.
Assuntos
Proteínas de Fase Aguda/metabolismo , Adipocinas/metabolismo , Aterosclerose/etiologia , Medicina Baseada em Evidências , Proteínas de Ligação a Ácido Graxo/metabolismo , Lipocalinas/metabolismo , Modelos Biológicos , Obesidade/fisiopatologia , Proteínas Proto-Oncogênicas/metabolismo , Adipocinas/sangue , Tecido Adiposo/imunologia , Tecido Adiposo/metabolismo , Animais , Aterosclerose/imunologia , Aterosclerose/metabolismo , Aterosclerose/prevenção & controle , Biomarcadores/sangue , Biomarcadores/metabolismo , Endotélio Vascular/imunologia , Endotélio Vascular/fisiopatologia , Proteínas de Ligação a Ácido Graxo/sangue , Humanos , Lipocalina-2 , Lipocalinas/sangue , Obesidade/imunologia , Obesidade/metabolismo , Obesidade/terapia , Proteínas Proto-Oncogênicas/sangueRESUMO
OBJECTIVE: Adipocyte fatty acid-binding-protein (A-FABP), retinol-binding protein 4 (RBP4), and lipocalin-2 have been identified as adipokines that may link obesity, insulin resistance, and metabolic syndrome. Nonalcoholic fatty liver disease (NAFLD) is regarded as a manifestation of metabolic syndrome. We evaluated the relationship of A-FABP, RBP4, and lipocalin-2 to variables related to metabolic syndrome and NAFLD. METHODS: A total of 140 subjects (72 males and 68 females) were included in this study. Subjects were divided into two groups (NAFLD, n = 73 and normal, n = 67) based on the detection of a fatty liver by ultrasonography. RESULTS: Serum A-FABP levels were higher in the NAFLD group than in the normal group (18.42 ± 7.24 ng/mL vs. 15.74 ± 7.02 ng/mL, p = 0.022). After adjusting for age and sex, we observed that body mass index (BMI), diastolic blood pressure, waist circumference, body fat percentage, triglycerides, and serum RBP4 levels were positively associated with serum A-FABP levels in all subjects. Multiple linear regression analysis revealed that systolic blood pressure, diastolic blood pressure, and serum RBP4 levels were independently associated with serum A-FABP levels. In logistic regression analysis, patients in the higher quartiles of A-FABP levels had higher odds ratios (OR) for the presence of NALFD than patients in the lower quartiles (OR: 3.56; 95% confident interval or CI: 1.25, 10.14). CONCLUSIONS: We observed higher serum A-FABP levels in the NAFLD group than in the normal group. However, serum RBP4 and lipocalin-2 levels appeared to have different relationships with several variables related to metabolic syndrome and NAFLD, which contradict results of previous studies.
Assuntos
Proteínas de Ligação a Ácido Graxo/sangue , Síndrome Metabólica/complicações , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Proteínas de Fase Aguda , Adulto , Biomarcadores/sangue , Estatura , Índice de Massa Corporal , Peso Corporal , Feminino , Humanos , Resistência à Insulina , Lipocalina-2 , Lipocalinas/sangue , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/etiologia , Valor Preditivo dos Testes , Proteínas Proto-Oncogênicas/sangue , Proteínas Plasmáticas de Ligação ao Retinol/metabolismo , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Triglicerídeos/sangue , Circunferência da CinturaRESUMO
Lipocalin families including lipocalin-2 and adipocyte fatty acid binding protein (A-FABP) were recently identified as novel adipokines to be associated with the cardiovascular risk variables of the metabolic syndrome. We evaluated the lipocalin-2 and A-FABP levels in 62 patients with essential hypertension (EHT) and 16 age-, gender- and body mass index-matched normotensive healthy subjects (NT). Furthermore, we evaluated the correlation between lipocalin-2, A-FABP levels, inflammatory markers including hsCRP and IL-10, and flow-mediated vasodilatation (FMD). In EHT, circulating lipocalin-2 levels were significantly higher than in NT (85.0 ± 37.6 ng/ml versus 43.8 ± 13.1 ng/ml, p < 0.001). However, A-FABP levels were not different between patients with EHT and NT. Serum lipocalin-2 levels were positively associated with SBP (r = 0.54, p < 0.001), DBP (r = 0.34, p = 0.003) and fasting glucose levels (r = 0.25, p = 0.032), On the other hand, circulating A-FABP levels were significantly associated with variables such as BMI, fasting insulin, insulin resistance index and hsCRP. Multiple linear regression analysis showed that mean arterial pressure was associated with fasting glucose, lipocalin-2 levels, age, BMI and hsCRP levels (R²= 0.456). However, circulating lipocalin-2 levels were not associated with FMD. In conclusion, lipocalin-2 levels were significantly higher in patients with EHT, and were independently associated with mean arterial pressure.
Assuntos
Proteínas de Ligação a Ácido Graxo/sangue , Hipertensão/sangue , Hipertensão/fisiopatologia , Lipocalinas/sangue , Proteínas Proto-Oncogênicas/sangue , Proteínas de Fase Aguda , Adulto , Glicemia/metabolismo , Pressão Sanguínea , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Hipertensão Essencial , Feminino , Humanos , Hipertensão/etiologia , Mediadores da Inflamação/sangue , Insulina/sangue , Resistência à Insulina , Interleucina-10/sangue , Lipocalina-2 , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/etiologia , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Análise de Regressão , Fatores de Risco , VasodilataçãoRESUMO
CONTEXT: Several cross-sectional studies have reported the association between serum adipocyte fatty acid binding protein (A-FABP) level and pre-sarcopenia. However, data on the impacts of serum A-FABP level and its changes over time on the development and improvement of pre-sarcopenia are scarce. METHODS: This longitudinal cohort study included 1496 adults (41.2% men; median age, 58 [53-63] years) in 2013-2014 and was followed up to 2015-2016. Participants underwent serum A-FABP level measurements at baseline and follow-up visit. Visceral fat area (VFA) was measured using magnetic resonance imaging. Skeletal muscle mass (SMM) was estimated by bioelectrical impedance analysis and converted to skeletal muscle index (SMI). Pre-sarcopenia was defined as SMI < 1 standard deviation of the sex-specific mean for the young reference group. RESULTS: During an average follow-up period of 2.1 years, baseline serum A-FABP level was positively associated with the incidence of pre-sarcopenia (standardized by weight: risk ratio [RR] 3.22, 95% confidence interval [CI] 1.96-5.38; standardized by VFA: RR 2.11, 95%CI 1.29-3.51) and negatively associated with the improvement of pre-sarcopenia (standardized by weight: RR 0.66, 95%CI 0.45-0.97; standardized by VFA: RR 0.71, 95%CI 0.54-0.94), regardless of whether SMM was standardized by weight or VFA. Moreover, changes in serum A-FABP level provided additional information on the incidence and improvement of pre-sarcopenia, independent of baseline serum A-FABP level (all P < 0.05). CONCLUSIONS: Baseline serum A-FABP level and its changes were positively associated with the incidence, and negatively associated with the improvement of pre-sarcopenia.
RESUMO
BACKGROUND AND PURPOSE: 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. EXPERIMENTAL APPROACH: 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. KEY RESULTS: 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. CONCLUSION AND IMPLICATIONS: 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.
Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Camundongos , Animais , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Metaloproteinase 9 da Matriz/metabolismo , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Simulação de Acoplamento Molecular , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/metabolismo , Proteínas de Ligação a Ácido Graxo/metabolismo , Fatores Imunológicos , AVC Isquêmico/metabolismo , Adipócitos/metabolismoRESUMO
BACKGROUND & AIMS: PPARγ plays an essential role in the transcriptional regulation of genes involved in lipid and glucose metabolism, insulin sensitivity, and inflammation. We recently demonstrated that PPARγ plays a causative role in hepatocyte lipid deposition, contributing to the pathogenesis of hepatic steatosis. In this study, we investigated the role of PPARγ in the inflammatory and fibrogenic response of the liver. METHODS: Heterozygous floxed/null Cre/LoxP mice with targeted deletion of PPARγ in either hepatocytes (Alb-Cre), macrophages (LysM-Cre) or hepatic stellate cells (HSCs) (aP2-Cre) were submitted to carbon tetrachloride (CCl4) liver injury. Further analyses were performed in precision-cut liver slices (PCLS) and primary cultures of hepatocytes, macrophages, and HSCs. RESULTS: LysM-Cre mice displayed an exacerbated response to chronic CCl4 injury and showed higher necroinflammatory injury, lipid peroxidation, inflammatory infiltrate, cleaved-caspase-3 and caspase 3/7 activity, and COX-2, TNF-α, CXCL2, and IL-1ß expression than Alb-Cre and control mice. The deleterious effects of PPARγ disruption in liver macrophages were confirmed in an acute model of CCl4 injury as well as in PCLS incubated with LPS. Moreover, LysM-Cre mice showed an aggravated fibrogenic response to CCl4, as revealed by more prominent Sirius Red and Masson's trichrome staining, elevated hydroxyproline content and induced α-SMA and TIMP-1 expression. Importantly, aP2-Cre mice with specific disruption of PPARγ in HSCs, as confirmed by immunocytochemical analysis of individual liver cells, also showed exacerbated liver damage and fibrogenic response to CCl4. CONCLUSIONS: These data unveil anti-inflammatory and anti-fibrogenic roles for PPARγ in non-parenchymal liver cells.