Background/Aims: Fatty acid-binding proteins (FABPs) are a family of intracellular lipid chaperones. Among FABPs, FABP1 (liver FABP) is expressed in proximal tubular epithelial cells in the kidney, and urinary FABP1 has been reported to reflect damage of proximal tubular epithelial cells. However, roles of other FABP isoforms in renal pathologies have not been reported. Recently, FABP4 (adipocyte FABP/aP2) was reported to be expressed in peritubular capillaries (PTCs), but not in glomerular capillaries in the normal kidney. We examined the hypothesis that pathological conditions alter the level and localization of FABP4 expression in the kidney, which mediates renal dysfunction. Methods: A total of 112 consecutive patients who underwent renal biopsy were retrospectively enrolled. Expression of FABP4 protein and mRNA in the kidney was examined by immunohistochemistry and in situ hybridization, respectively. The ratio of FABP4-positive area to total area within glomeruli (G-FABP4-Area), urinary protein level (U-Protein), and change in estimated glomerular filtration rate (eGFR) 1 year after biopsy were examined. Results: FABP4 protein and mRNA were expressed not only in PTCs, but also in endothelial cells and macrophages in the glomerulus. G-FABP4-Area was correlated with U-Protein (r = 0.497, p < 0.001). As a subanalysis, in patients with IgA nephropathy (n = 34), G-FABP4-Area was significantly larger in cases with an endocapillary proliferative lesion, and change in eGFR was negatively correlated with G-FABP4-Area at baseline (r = -0.537, p = 0.008). Conclusion: Ectopic FABP4 expression in the glomerulus is induced by renal diseases and is closely associated with proteinuria and renal dysfunction.

Furuhashi M, Hotamisligil GS: Fatty acid-binding proteins: role in metabolic diseases and potential as drug targets. Nat Rev Drug Discov 2008;7:489-503.
Furuhashi M, Ishimura S, Ota H, Miura T: Lipid chaperones and metabolic inflammation. Int J Inflam 2011;2011:642612.
Maatman RG, van de Westerlo EM, van Kuppevelt TH, Veerkamp JH: Molecular identification of the liver- and the heart-type fatty acid-binding proteins in human and rat kidney. Use of the reverse transcriptase polymerase chain reaction. Biochem J 1992;288:285-290.
Kamijo-Ikemori A, Sugaya T, Kimura K: Urinary fatty acid binding protein in renal disease. Clin Chim Acta 2006;374:1-7.
Noiri E, Doi K, Negishi K, Tanaka T, Hamasaki Y, Fujita T, Portilla D, Sugaya T: Urinary fatty acid-binding protein 1: an early predictive biomarker of kidney injury. Am J Physiol Renal Physiol 2009;296:F669-F679.
Araki S, Haneda M, Koya D, Sugaya T, Isshiki K, Kume S, Kashiwagi A, Uzu T, Maegawa H: Predictive effects of urinary liver-type fatty acid-binding protein for deteriorating renal function and incidence of cardiovascular disease in type 2 diabetic patients without advanced nephropathy. Diabetes Care 2013;36:1248-1253.
Mou S, Wang Q, Li J, Shi B, Ni Z: Urinary excretion of liver-type fatty acid-binding protein as a marker of progressive kidney function deterioration in patients with chronic glomerulonephritis. Clin Chim Acta 2012;413:187-191.
Hotamisligil GS, Johnson RS, Distel RJ, Ellis R, Papaioannou VE, Spiegelman BM: Uncoupling of obesity from insulin resistance through a targeted mutation in aP2, the adipocyte fatty acid binding protein. Science 1996;274:1377-1379.
Makowski L, Boord JB, Maeda K, Babaev VR, Uysal KT, Morgan MA, Parker RA, Suttles J, Fazio S, Hotamisligil GS, Linton MF: Lack of macrophage fatty-acid-binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis. Nat Med 2001;7:699-705.
Furuhashi M, Fucho R, Gorgun CZ, Tuncman G, Cao H, Hotamisligil GS: Adipocyte/macrophage fatty acid-binding proteins contribute to metabolic deterioration through actions in both macrophages and adipocytes in mice. J Clin Invest 2008;118:2640-2650.
Furuhashi M, Tuncman G, Gorgun CZ, Makowski L, Atsumi G, Vaillancourt E, Kono K, Babaev VR, Fazio S, Linton MF, Sulsky R, Robl JA, Parker RA, Hotamisligil GS: Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2. Nature 2007;447:959-965.
Elmasri H, Karaaslan C, Teper Y, Ghelfi E, Weng M, Ince TA, Kozakewich H, Bischoff J, Cataltepe S: Fatty acid binding protein 4 is a target of VEGF and a regulator of cell proliferation in endothelial cells. FASEB J 2009;23:3865-3873.
Lee MY, Tse HF, Siu CW, Zhu SG, Man RY, Vanhoutte PM: Genomic changes in regenerated porcine coronary arterial endothelial cells. Arterioscler Thromb Vasc Biol 2007;27:2443-2449.
Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Yamagata K, Tomino Y, Yokoyama H, Hishida A: Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis 2009;53:982-992.
Roberts IS, Cook HT, Troyanov S, Alpers CE, Amore A, Barratt J, Berthoux F, Bonsib S, Bruijn JA, Cattran DC, Coppo R, D'Agati V, D'Amico G, Emancipator S, Emma F, Feehally J, Ferrario F, Fervenza FC, Florquin S, Fogo A, Geddes CC, Groene HJ, Haas M, Herzenberg AM, Hill PA, Hogg RJ, Hsu SI, Jennette JC, Joh K, Julian BA, Kawamura T, Lai FM, Li LS, Li PK, Liu ZH, Mackinnon B, Mezzano S, Schena FP, Tomino Y, Walker PD, Wang H, Weening JJ, Yoshikawa N, Zhang H: The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility. Kidney Int 2009;76:546-556.
Iso T, Maeda K, Hanaoka H, Suga T, Goto K, Syamsunarno MR, Hishiki T, Nagahata Y, Matsui H, Arai M, Yamaguchi A, Abumrad NA, Sano M, Suematsu M, Endo K, Hotamisligil GS, Kurabayashi M: Capillary endothelial fatty acid binding proteins 4 and 5 play a critical role in fatty acid uptake in heart and skeletal muscle. Arterioscler Thromb Vasc Biol 2013;33:2549-2557.
Satchell SC, Braet F: Glomerular endothelial cell fenestrations: an integral component of the glomerular filtration barrier. Am J Physiol Renal Physiol 2009;296:F947-F956.
Deen WM, Lazzara MJ, Myers BD: Structural determinants of glomerular permeability. Am J Physiol Renal Physiol 2001;281:F579-F596.
Brinkkoetter PT, Ising C, Benzing T: The role of the podocyte in albumin filtration. Nat Rev Nephrol 2013;9:328-336.
Sun YB, Qu X, Zhang X, Caruana G, Bertram JF, Li J: Glomerular endothelial cell injury and damage precedes that of podocytes in adriamycin-induced nephropathy. PLoS One 2013;8:e55027.
Toyoda M, Najafian B, Kim Y, Caramori ML, Mauer M: Podocyte detachment and reduced glomerular capillary endothelial fenestration in human type 1 diabetic nephropathy. Diabetes 2007;56:2155-2160.
Yuen DA, Stead BE, Zhang Y, White KE, Kabir MG, Thai K, Advani SL, Connelly KA, Takano T, Zhu L, Cox AJ, Kelly DJ, Gibson IW, Takahashi T, Harris RC, Advani A: eNOS deficiency predisposes podocytes to injury in diabetes. J Am Soc Nephrol 2012;23:1810-1823.
Lee MY, Li H, Xiao Y, Zhou Z, Xu A, Vanhoutte PM: Chronic administration of BMS309403 improves endothelial function in apolipoprotein e-deficient mice and in cultured human endothelial cells. Br J Pharmacol 2011;162:1564-1576.
Yamashita T, Fujimiya M, Nagaishi K, Ataka K, Tanaka M, Yoshida H, Tsuchihashi K, Shimamoto K, Miura T: Fusion of bone marrow-derived cells with renal tubules contributes to renal dysfunction in diabetic nephropathy. FASEB J 2012;26:1559-1568.
Gorriz JL, Martinez-Castelao A: Proteinuria: detection and role in native renal disease progression. Transplant Rev (Orlando) 2012;26:3-13.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.