scholarly journals High serum levels of fatty acid–binding protein 7 in diabetic rats with experimental sepsis

2018 ◽  
Vol 16 ◽  
pp. 205873921876423
Author(s):  
Emerson R Martins ◽  
Thais M de Lima ◽  
Hermes V Barbeiro ◽  
Marcel C César Machado ◽  
Fabiano Pinheiro da Silva

Sepsis is a disease that affects a wide variety of individuals, including the young, the elderly, and those admitted to the hospital with diverse acute or chronic conditions. Because sepsis is such a heterogeneous disease, some researchers believe that personalized medicine may represent a promising means of improving the prognosis for certain patients. Of those who develop sepsis, diabetic patients remain a significant proportion, because diabetes is a metabolic disorder that is associated with disturbances in the immune system, which facilitates bacterial infections. Fatty acid–binding proteins (FABPs) are a family of transport proteins with an important role in metabolism; therefore, we decided to measure their levels in diabetic rats, as part of a search for a novel biomarker of sepsis. Diabetes was experimentally induced in male Wistar rats, some of which then underwent cecal ligation and puncture, and the levels of FABP4 and FABP7 were measured in their serum and key tissues. Serum FABP7 levels in diabetic septic rats were significantly higher than those in non-diabetic septic rats. Consequently, we propose that FABP7 should be further investigated as a potential biomarker of sepsis in diabetic patients.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Abdelrahman Zamzam ◽  
Muzammil H. Syed ◽  
John Harlock ◽  
John Eikelboom ◽  
Krishna K. Singh ◽  
...  

AbstractPlasma levels of fatty acid binding protein 3 (pFABP3) are elevated in patients with peripheral artery disease (PAD). Since the kidney filters FABP3 from circulation, we investigated whether urinary fatty acid binding protein 3 (uFABP3) is associated with PAD, and also explored its potential as a diagnostic biomarker for this disease state. A total of 130 patients were recruited from outpatient clinics at St. Michael’s Hospital, comprising of 65 patients with PAD and 65 patients without PAD (non-PAD). Levels of uFABP3 normalized for urine creatinine (uFABP3/uCr) were 1.7-folds higher in patients with PAD [median (IQR) 4.41 (2.79–8.08)] compared with non-PAD controls [median (IQR) 2.49 (1.78–3.12), p-value = 0.001]. Subgroup analysis demonstrated no significant effect of cardiovascular risk factors (age, sex, hypertension, hypercholesteremia, diabetes and smoking) on uFABP3/uCr in both PAD and non-PAD patients. Spearmen correlation studies demonstrated a significant negative correlation between uFABP3/uCr and ABI (ρ = − 0.436; p-value = 0.001). Regression analysis demonstrated that uFABP3/Cr levels were associated with PAD independently of age, sex, hypercholesterolemia, smoking, prior history of coronary arterial disease and Estimated Glomerular Filtration rate (eGFR) [odds ratio: 2.34 (95% confidence interval: 1.47–3.75) p-value < 0.001]. Lastly, receiver operator curve (ROC) analysis demonstrated unadjusted area under the curve (AUC) for uFABP3/Cr of 0.79, which improved to 0.86 after adjusting for eGFR, age, hypercholesteremia, smoking and diabetes. In conclusion, our results demonstrate a strong association between uFABP3/Cr and PAD and suggest the potential of uFABP3/Cr in identifying patients with PAD.


1999 ◽  
Vol 337 (3) ◽  
pp. 407-414 ◽  
Author(s):  
Maurice M. A. L. PELSERS ◽  
Jan T. LUTGERINK ◽  
Frans A. van NIEUWENHOVEN ◽  
Narendra N. TANDON ◽  
Ger J. van der VUSSE ◽  
...  

The rat membrane protein fatty acid translocase (FAT), which shows sequence similarity to human CD36 (a membrane protein supposedly involved in a variety of membrane processes), is implicated in the transport of long-chain fatty acids across cellular membranes. To set up an immunoassay for quantification of FAT in different tissues, we isolated a series of anti-FAT antibodies by panning a large naive phage antibody library on FAT-transfected H9c2 cells. All seven different phage antibody fragments isolated reacted specifically with FAT, and most likely recognize the same or closely located immunodominant sites on FAT, as a competitive monoclonal antibody (mAb) (CLB-IV7) completely blocked the binding of all these phage antibodies to cells. A sandwich ELISA was set up using mAb 131.4 (directed against purified CD36 from human platelets) as capture antibody and phage antibodies and anti-phage sera as detector. With this ELISA (sensitivity 0.05 µg/ml), the FAT content in isolated cardiomyocytes was found to be comparable with that of total heart (≈ 3 mg/g of protein), while liver tissue and endothelial cells were below the detection limit (< 0.1 mg of FAT/g of protein). During rat heart development, protein levels of FAT rose from 1.7±0.7 mg/g of protein on the day before birth to 3.6±0.4 mg/g of protein on day 70. Comparing control with streptozotocin-induced diabetic rats, a statistically significant (P< 0.05) 2–4-fold increase of FAT was seen in heart (from 4.2±2.3 to 11.0±5.7 mg/g of protein), soleus (from 0.6±0.1 to 1.4±0.5 mg/g of protein) and extensor digitorum longus (EDL) muscle (from 0.3±0.1 to 1.2±0.8 mg/g of protein). In addition, the FAT contents of each of these muscles were found to be of similar magnitude to the contents of cytoplasmic heart-type fatty-acid-binding protein in both diabetic rats and controls, supporting the suggested roles of these two proteins in cellular fatty acid metabolism. This is the first time phage display technology has been succesfully applied for direct selection, from a large naive antibody library, of antibodies that recognize selected membrane proteins in their natural context.


Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 227 ◽  
Author(s):  
Marcin Trojnar ◽  
Jolanta Patro-Małysza ◽  
Żaneta Kimber-Trojnar ◽  
Bożena Leszczyńska-Gorzelak ◽  
Jerzy Mosiewicz

There is ample scientific evidence to suggest a link between the fatty acid-binding protein 4 (FABP4) and insulin resistance, gestational (GDM), and type 2 (T2DM) diabetes mellitus. This novel proinflammatory adipokine is engaged in the regulation of lipid metabolism at the cellular level. The molecule takes part in lipid oxidation, the regulation of transcription as well as the synthesis of membranes. An involvement of FABP4 in the pathogenesis of obesity and insulin resistance seems to be mediated via FABP4-dependent peroxisome proliferator-activated receptor γ (PPARγ) inhibition. A considerable number of studies have shown that plasma concentrations of FABP4 is increased in obesity and T2DM, and that circulating FABP4 levels are correlated with certain clinical parameters, such as body mass index, insulin resistance, and dyslipidemia. Since plasma-circulating FABP4 has the potential to modulate the function of several types of cells, it appears to be of extreme interest to try to develop potential therapeutic strategies targeting the pathogenesis of metabolic diseases in this respect. In this manuscript, representing a detailed review of the literature on FABP4 and the abovementioned metabolic disorders, various mechanisms of the interaction of FABP4 with insulin signaling pathways are thoroughly discussed. Clinical aspects of insulin resistance in diabetic patients, including women diagnosed with GDM, are analyzed as well.


Metabolism ◽  
2019 ◽  
Vol 96 ◽  
pp. 12-21 ◽  
Author(s):  
Ricardo Rodríguez-Calvo ◽  
Josefa Girona ◽  
Marina Rodríguez ◽  
Sara Samino ◽  
Emma Barroso ◽  
...  

PLoS ONE ◽  
2015 ◽  
Vol 10 (5) ◽  
pp. e0126990 ◽  
Author(s):  
Naohiko Imai ◽  
Takashi Yasuda ◽  
Atsuko Kamijo-Ikemori ◽  
Yugo Shibagaki ◽  
Kenjiro Kimura

2008 ◽  
Vol 54 (1) ◽  
pp. 181-187 ◽  
Author(s):  
Anna Cabré ◽  
Iolanda Lázaro ◽  
Josefa Girona ◽  
Josep M Manzanares ◽  
Francesc Marimón ◽  
...  

Abstract Background: 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. Methods: 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 &lt;30 mL/min/1.73 m2) or albuminuria were not included. Results: FABP4 concentrations were higher in diabetic patients with MDRD-GFR &lt;60 mL/min/1.73 m2 (P &lt;0.001). We observed a significant, direct correlation between FABP4 and creatinine (r = 0.446, P &lt;0.001) and an inverse correlation between FABP4 and MDRD-GFR (r = −0.511, P &lt;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 &lt;0.001 and r = −0.510, P &lt;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. Conclusions: 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.


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