Urine liver fatty acid binding protein and chronic kidney disease progression

Excretion of the tubular protein liver fatty acid binding protein (L-FABP) is a potential novel biomarker of renal dysfunction. We examined whether urine L-FABP excretion adds prognostic information to the well-established risk markers, blood pressure (BP), albumin excretion and baseline GFR, regarding progression of chronic kidney disease (CKD). In a prospective study design a cohort of 74 stage 3-4 CKD patients (age 61?±?13 years) were included. Glomerular filtration ratio (GFR, ⁵¹Cr-EDTA-clearance), 24-hour ambulatory BP, 24-hour urinary albumin/creatinine ratio (UAC) and urinary L-FABP/creatinine ratio (U-L-FABP/C) were determined at baseline and after 18 months of follow-up. For comparison 25 age-matched healthy controls were included. The U-L-FABP/C was elevated in CKD patients when compared to controls (mean U-L-FABP/C 2.3 [95% CI 1.7–2.9] μg/mmol vs 0.6 [0.5–0.7] μg/mmol, p?<?.001). In CKD patients, log U-L-FABP/C at baseline and at follow-up were positively associated (Pearson correlation coefficient r?=?0.74, p?<?.001). Baseline log U-L-FABP/C was negatively correlated with baseline GFR (r?=??0.32, p?<?.001) and directly correlated with UAC (r?=?0.67, p?<?.001). The relative change in GFR from baseline to follow-up correlated with baseline UAC (p?<?.001), 24-hour systolic BP (p?=?0.05) and log U-L-FABP/C (p?<?.001). Using multiple regression analysis adjusting for baseline GFR, UAC, BP, age and gender, baseline log U-L-FABP/C was associated with a decline in GFR only in patients with UAC <3?mg/mmol (n?=?29, p?=?0.001) and not in patients with UAC ≥3?mg/mmol (n?=?44, p?=?0.21). In conclusion urine L-FABP/C is permanently elevated in CKD patients, but only associated with GFR decline in those without albuminuria.     

Urinary fatty acid-binding protein as a new clinical marker of the progression of chronic renal disease

Previous studies have indicated that in massive proteinuria, free fatty acids (FFAs) bound to albumin were overloaded in the proximal tubule and exacerbated tubulointerstitial damage. Liver-type fatty acid-binding protein (L-FABP) is an intracellular carrier protein of FFAs that is expressed in the proximal tubule of human kidney. We sought to evaluate urinary L-FABP as a clinical marker in chronic renal disease. Urinary L-FABP was measured in patients with nondiabetic chronic renal disease (n = 120) with the use of a newly established ELISA method. We then monitored these patients for 15 to 51 months. Clinical data were analyzed with multivariate analysis. Urinary L-FABP was correlated with urinary protein, urinary alpha(1)-microglobulin, and serum creatinine concentrations. Urinary L-FABP at the start of follow-up (F = 17.1, r =.36, P <.0001) was selected as a significant clinical factor correlated with the progression rate, defined as a slope of a reciprocal of serum creatinine over time. We next selected the patients with mild renal dysfunction (n = 35) from all 120 patients and divided them into 2 groups according to progression rate: the progression group (n = 22) and the nonprogression group (n = 13). Serum creatinine and urinary protein concentrations and blood pressure at the start of follow-up were higher in the progression group than in the nonprogression group, although we detected no significant difference between the 2 groups. Urinary L-FABP was significantly higher in the former group than in the latter (P <.05). The results showed that urinary L-FABP reflected the clinical prognosis of chronic renal disease. Urinary L-FABP may be a clinical marker that can help predict the progression of chronic glomerular disease.     

Adiponectin, adipocyte fatty acid binding protein, and epidermal fatty acid binding protein: proteins newly identified in human breast milk

BACKGROUND: Breastfeeding may protect children from developing metabolic syndrome and other diseases later in life. We investigated novel proteins in human breast milk that might play a role in this process. METHODS: We used ELISA to measure adiponectin, adipocyte and epidermal fatty acid binding proteins (AFABP, EFABP), and leptin concentrations in human breast milk obtained from 59 mothers 48 h after initiation of lactation. Using a questionnaire and medical records, we collected information about the mothers and newborns. RESULTS: Mean (SE) adiponectin concentrations in breast milk were 13.7 (0.8), range 3.9-30.4 microg/L; AFABP concentrations 26.7 (4.4), range 1.2-137.0 microg/L; EFABP concentrations 18.1 (1.4), range 0.8-47.0 microg/L; and leptin concentrations 0.50 (0.05), range 0-1.37 microg/L. We found a significant correlation between AFABP and EFABP concentrations (r = 0.593, P <0.0001). Maternal EFABP concentrations were significantly higher in mothers who delivered boys than in those who delivered girls [21.7 (2.3) vs 15.4 (1.7) microg/L, P = 0.028] and correlated with newborn birth weight (r = 0.266, P = 0.045). Maternal leptin correlated with body weight before pregnancy (r = 0.272, P = 0.043) and at delivery (r = 0.370, P = 0.005), body mass index before pregnancy (r = 0.397, P = 0.003) and at delivery (r = 0.498, P <0.0001), body weight gain during pregnancy (r = 0.267, P = 0.047), and newborn gestational age (r = 0.266, P = 0.048). Leptin was significantly lower in mothers who delivered preterm vs term babies [0.30 (0.09) vs 0.60 (0.05) ug/L, P = 0.026]. CONCLUSIONS: Concentrations of adiponectin, AFABP, and EFABP in human breast milk are related to nutritional variables of mothers and newborns and thus may play a role in the protective effects of breastfeeding.     

Heart-type fatty acid binding protein in elective cardioversion of atrial fibrillation

Objectives

We sought to investigate whether heart-type fatty acid binding protein (H-FABP), a new marker of myocardial necrosis, increases in relation to elective cardioversion of atrial fibrillation (AF).

Methods

We studied 25 consecutive patients (61 ± 16 years old, 21 men) admitted to our hospital for elective cardioversion of AF. Peripheral venous samples were drawn immediately before cardioversion, one hour and 24 h after the procedure and assayed for H-FABP.

Results

A mean of 309 ± 183 J was used for cardioversion. Successful cardioversion in sinus rhythm was achieved in 18 patients (72%). Serum levels of H-FABP did not change significantly either in relation to the procedure [1385 (256–17,127) pg/mL at baseline, 1125 (290–15,238) pg/mL 1 h post and 1045.5 (66–2981) pg/mL 24 h post cardioversion, p = 0.37] or to the success of the procedure.

Conclusion

H-FABP does not significantly change following elective cardioversion for AF and we, therefore, speculate that myocardial necrosis does not occur during cardioversion.     

小肠脂肪酸结合蛋白基因多态性与冠心病患者血脂水平关系的研究

目的探讨小肠型脂肪酸结合蛋白（FABP2）外显子2第54位密码子的基因多态性与不同民族冠心病患者血脂水平的关系。方法收集人选人群的空腹外周血标本,全血用于提取DNA,血清用于检测血脂。采用聚合酶链反应（PCR）,DNA限制性内切酶酶切（RFLP）等技术,分别对病例组（汉族冠心病组60例,蒙古族冠心病组60例）和对照组（汉族对照组51例,蒙古族对照组51例）54A／TFABP2基因型进行分析。结果（1）汉族冠心病组人群54T等位基因频率为0．542,54A等位基因频率为0．458;蒙古族冠心病人群54T等位基因频率为0．708,54A等位基因频率为0．292;汉族对照组人群54T等位基因频率为0．284,54A等位基因频率为0．716;蒙古族对照组人群54T等位基因频率为0．353,54A等位基因频率为0．647;与对照组相比：汉族及蒙古族冠心病组人群突变型54T等位基因频率明显增高,且差异均有统计学意义（统计值分别为：X2=14．967,P〈0．05;x2=28．083,P〈0．05）;蒙古族冠心病人群突变型54T等位基因频率较汉族冠心病人群增高,且差异有统计学意义（X2=7．111,P〈0．05）。（2）与FABP2Thr54（-）者相比,冠心病组FABP2Thr54（＋）者的空腹血浆TG[汉族冠心病：Thr54（-）人群为（1．89±0．57）mmol／L,Thr54（＋）人群为（3．92±1．63）mmoL／L,P=0．001;蒙古族冠心病组：Thr54（-）人群为（2．23±0．13）mmol／L,Thr54（＋）人群为（4．03±1．14）mmol／L,P=0．035]、低密度脂蛋白胆固醇[汉族冠心病：Thr54（-）人群为（3．09±0．92）mmol／L,Thr54（＋）人群为（4．05±1．14）mmol／L,P=0．025;蒙古族冠心病组：Thr54（-）人群为（4．26±0．08）mmol／L,Thr54（＋）人群为（5．104-0．56）mmol／L,P=0．045]水平升高。结论（1）内蒙古自治区呼和浩特市市区蒙古族及汉族人群中存在FABP2外显子2第54位密码子的基因多态性。（2）FABP2基因多态性是冠心病患者脂质代谢异常的影响因素,可能与冠心病发病风险有关,携带FABP2Thr基因的蒙古族个体冠心病发病风险增高。     

心型脂肪酸结合蛋白在早期急性心肌梗死中的诊断价值

目的 探讨心型脂肪酸结合蛋白（H-FABP）在早期急性心肌梗死中的诊断价值.方法 选择我院收治的疑为AMI胸痛患者126例,进行H-FABP、cTnT及CK-MB检测.结果 34例AMI患者发病3h内血液H-FABP检测灵敏度和准确性显著高于cTnT和CK-MB,差异有统计学意义（P＜0.05）;48例AMI患者发病3-6 h血液HFABP检测灵敏度和准确性显著高于cTnT,差异有统计学意义（P＜0.05）,但与CK-MB比较,差异无统计学意义（P＞0.05）.非AMI患者H-FABP在以上两个时间段均为正常值.结论 H-FABP用于早期诊断急性心肌梗死准确性高,值得临床推广.     

An amino acid substitution in the human intestinal fatty acid binding protein is associated with increased fatty acid binding, increased fat oxidation, and insulin resistance.

The intestinal fatty acid binding protein locus (FABP2) was investigated as a possible genetic factor in determining insulin action in the Pima Indian population. A polymorphism at codon 54 of FABP2 was identified that results in an alanine-encoding allele (frequency 0.71) and a threonine-encoding allele (frequency 0.29). Pimas who were homozygous or heterozygous for the threonine-encoding allele were found to have a higher mean fasting plasma insulin concentration, a lower mean insulin-stimulated glucose uptake rate, a higher mean insulin response to oral glucose and a mixed meal, and a higher mean fat oxidation rate compared with Pimas who were homozygous for the alanine-encoding allele. Since the FABP2 threonine-encoding allele was found to be associated with insulin resistance and increased fat oxidation in vivo, we further analyzed the FABP2 gene products for potential functional differences. Titration microcalorimetry studies with purified recombinant protein showed that the threonine-containing protein had a twofold greater affinity for long-chain fatty acids than the alanine-containing protein. We conclude that the threonine-containing protein may increase absorption and/or processing of dietary fatty acids by the intestine and thereby increase fat oxidation, which has been shown to reduce insulin action.     

Urinary monocyte chemoattractant protein-1 in renal disease

Monocyte chemoattractant protein-1 (MCP-1/CCL2) has a critical role in the development of various renal diseases. Data from disease specific experimental animal models and clinical studies confirm that MCP-1 plays an important part in the pathogenesis of renal diseases. The action of MCP-1 in these studies has been shown to be more complex than the traditional concept of monocyte/macrophage recruitment to the inflammatory site. MCP-1 is expressed in renal tissues and it is detectable in urine of patients with a variety of renal diseases. Measurement of urinary levels of MCP-1 can provide valuable information not only for the diagnosis of active renal disease, but also for monitoring of response to therapy. Urinary MCP-1 measurement can provide help with evaluation of the prognosis in various renal diseases. Furthermore, selective targeting of MCP-1 could be an effective treatment in suppressing a number of renal diseases as blocking MCP-1 has already been shown to ameliorate renal diseases in experimental animal models. The advantage of measuring urinary MCP-1 rather than the conventional markers must now be validated using a larger cohort of patients in different renal diseases. Also the therapeutic potential of MCP-1 targeting agents needs to be investigated in clinical studies.     

血液透析患者血清脂肪细胞型脂肪酸结合蛋白水平与动脉粥样硬化相关性的初步探讨

目的 观察血液透析（hemodialysis,HD）患者血清脂肪细胞型脂肪酸结合蛋白（adiopocyte fatty acid binding protein,A-FABP,FABP4）的变化,并初步探讨其与HD动脉粥样硬化（atherosclerosis,AS）的相关性.方法 选取HD患者29例为研究对象（HD组）,20例健康体检者为对照（HC组）,应用酶联免疫吸附试验（ELISA）测定2组血清A-FABP、白细胞介素-6（interleukin-6,IL-6）、单核细胞趋化蛋白-1（monocyte chemotactic protein 1,MCP-1）的水平.采用彩色多普勒超声技术测定患者颈总动脉内膜-中层（intima-media thickness,IMT）厚度.再根据是否伴有大血管病变,将HD组分为HD合并AS组（HD＋AS组）、HD不合并AS组（HD-AS组）.结果 HD组患者与HC组比较,血清A-FABP、FFA水平显著升高（P＜0.05）.经pearson相关分析,A-FABP与FFA存在显著相关（r=0.939,P＜0.01）,A-FABP与IL-6、MCP-1亦存在正相关关系.HD＋AS组患者血清A-FABP水平高于CKD-AS组,且存在统计学差异（P＜0.01）.结论 HD患者血清A-FABP及FFA水平高于健康人群,AS的形成可能与血清A-FABP水平的升高有关.推测A-FABP可能主要通过促进炎症反应和活化巨噬细胞参与AS的形成.     

Serum retinol binding protein 4 and galectin-3 binding protein as novel markers for postmenopausal nonalcoholic fatty liver disease

ObjectiveTo investigate the differential protein expression before and after menopause in women with nonalcoholic fatty liver disease (NAFLD) and to explore novel markers for menopausal NAFLD.MethodsEight serum samples collected from pre- or post-menopausal women with NAFLD were analysed by iTRAQ 2D-LC-MS/MS. Two protein candidates were selected and verified by enzyme-linked immunosorbent assay (ELISA) in serum samples collected from a one hundred and fifty-three female population subsequently, including 51 in post-menopausal status with NAFLD, 41 in pre-menopausal with NAFLD, 19 healthy individuals in post-menopausal status and 42 healthy pre-menopausal women.ResultsA total of one hundred and sixty-seven proteins exhibiting significant changes were characterized, among which sixty-five were up-regulated and one hundred and two were down-regulated. Of those altered proteins, the expression of serum retinol binding protein 4 (RBP4) and galectin-3 binding protein (LGALS3BP) was obviously increased in the post-menopausal patient group compared to the other. ELISA validations for the two proteins were consistent with the proteomic profiling.ConclusionsSerum RBP4 and LGAL3BP were up-regulated after menopause under NAFLD conditions, which suggested the two proteins may be potential markers as NAFLD in postmenopausal population.     

Fatty acid binding protein. Role in esterification of absorbed long chain fatty acid in rat intestine.

Fatty acid binding protein (FABP) is a protein of 12,000 mol wt found in cytosol of intestinal mucosa and other tissues, which exhibits high affinity for long chain fatty acids. It has been suggested that FABP (which may comprise a group of closely related proteins of 12,000 mol wt) participates in cellular fatty acid transport and metabolism. Although earlier findings were consistent with this concept, the present studies were designed to examine its physiological function more directly. Everted jejunal sacs were incubated in mixed fatty acid-monoglyceride-bile acid micelles, in the presence or absence of equimolar concentrations of either of two compounds which inhibit oleate binding to FABP:flavaspidic acid-N-methyl-glucaminate and alpha-bromopalmitate. Oleate uptake, mucosal morphology, and oxidation of [14C]acetate remained unaffected by these agents, but oleate incorporation into triglyceride was inhibited by 62-64% after 4 min. The inhibition by flavaspidic acid was reversible with higher oleate concentrations. The effect of these compounds on enzymes of triglyceride biosynthesis was examined in intestinal microsomes. Neither flavaspidic acid nor alpha-bromopalmitate inhibited acyl CoA:monoglyceride acyl-transferase. Fatty acid:coenzyme A ligase activity was significantly enhanced in the presence of partially purified FABP, probably reflecting a physical effect on the fatty acid substrate or on the formation of the enzyme-substrate complex. Activity of the enzyme in the presence of 0.1 mM oleate was only modestly inhibited by equimolar flavaspidic acid and alpha-bromopalmitate, and this effect was blunted or prevented by FABP. We conclude that in everted gut sacs, inhibition of triglyceride synthesis by flavaspidic acid and alpha-bromopalmitate could not be explained as an effect on fatty acid uptake or on esterifying enzymes in the endoplasmic reticulum but rather can be interpreted as reflecting inhibition of fatty acid binding to FABP. These findings lend further support to the concept that FABP participates in cellular fatty acid transport and metabolism. It is also possible that FABP, by effecting an intracellular compartmentalization of fatty acids and acyl CoA, may play a broader role in cellular lipid metabolism.     

心型脂肪酸结合蛋白对老年人全因死亡的预测价值

目的探索心型脂肪酸结合蛋白(H-FABP)在老年人群全因死亡中的预测作用。方法纳入65岁以上不伴冠心病的老年体检人群568例,入组时均进行基线资料采集及血清H-FABP水平的测定,共随访7年,分析H-FABP与死亡及主要不良心血管事件之间的关系。结果随访期间,全因死亡31例,无心血管死亡,发生主要不良心血管事件33例。H-FABP对于全因死亡的预测效能高于尿素氮(BUN)、估算肾小球滤过率(e GFR)和血清白蛋白水平,并且H-FABP>3.57μg/L可能作为全因死亡的独立危险因素。生存分析结果显示越高的H-FABP水平意味着越高的死亡风险。结论 H-FABP与老年人群的全因死亡相关。     

Heart-type fatty acid binding protein as a marker of reperfusion after thrombolytic therapy

Accurate, rapid, and simple noninvasive measures of infarct-related artery (IRA) patency are needed to identify patients with failed coronary reperfusion for rescue percutaneous coronary intervention (PCI). Heart-type Fatty Acid Binding Protein (H-FABP) is a small, cytosolic protein found in high concentrations in the myocardium. We evaluated the efficacy of H-FABP as a marker for successful reperfusion after thrombolysis. Fifty-eight subjects from the TIMI 14 trial had H-FABP and myoglobin concentrations measured at baseline (immediately prior to thrombolysis) and 60, 90, and 180 min after thrombolysis. All patients underwent coronary angiography at 90 min. By 60 min after thrombolysis, median concentrations of H-FABP and myoglobin were significantly higher in patients with a patent IRA than in those with an occluded IRA (P<0.01 for each). Similarly, the 60 and 90 min/baseline H-FABP and myoglobin ratios were significantly higher among patients with a patent IRA (P<0.01 for each). There were no significant differences in marker concentrations or ratios between patients with TIMI grade 2 and TIMI grade 3 flow. The area under the ROC curve tended to be greater for the 60 and 90 min/baseline myoglobin ratios than for similar ratios of H-FABP (0.71 and 0.73 vs. 0.64 and 0.62; P=ns). In conclusion, successful reperfusion can be detected within the first 60 min after thrombolysis with either H-FABP or myoglobin. Despite a favorable kinetic profile, however, H-FABP does not appear to represent a significant advance over myoglobin in the noninvasive detection of reperfusion after thrombolysis.