problendoПроблемы ЭндокринологииProblems of Endocrinology0375-96602308-1430Endocrinology Research Centre10.14341/probl201258448-53problendo-4678Research ArticleСтатьиArticlesРоль специфических шаперонов в патогенезе ожирения и ассоциированных с ним заболеванийThe role of specific chaperons in pathogenesis of obesity and related diseasesVasiukovaO V-OkorokovP Lpokorokov@gmail.com201215082012584ТОМ 58, №4 (2012)4853Copyright © Vasiukova O.V., Okorokov P.L., 20122012Vasiukova O.V., Okorokov P.L.Vasiukova O.V., Okorokov P.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.probl-endojournals.ru/jour/article/view/4678

Ожирение, сахарный диабет 2-го типа и атеросклероз связаны с развитием "метаболического" воспаления. В адипоцитах и макрофагах провоспалительные механизмы могут быть инициированы как внеклеточными медиаторами (цитокины, насыщенные жирные кислоты), так и внутриклеточными компонентами (стресс эндоплазматического ретикулума, избыточная продукция свободных радикалов). Важную роль в развитии "метаболического" воспаления играют внутриклеточные белки - переносчики жирных кислот ("fatty acid-binding proteins").

Obesity, type 2 diabetes mellitus, and atherosclerosis are associated with the development of "metabolic" inflammation. The proinflammatory mechanisms in adipocytes and macrophages are initiated by both extracellular mediators (cytokines, saturated fatty acids) and intracellular processes (endoplasmic reticulum stress, excessive production of free radicals). An important role in the development of "metabolic" inflammation is played by protein transporters of fatty acids ("fatty acid-binding proteins").

ожирение"метаболическое" воспалениешапероныobesitymetabolic inflammationchaperonsReferencesHotamisligil G.S. Inflammation and metabolic disorders. Nature 2006; 444: 7121: 860-867.Hotamisligil G.S. Inflammation and metabolic disorders. Nature 2006; 444: 7121: 860-867.Gregor M.F., Hotamisligil G.S. Inflammatory mechanisms in obesity. Ann Review Immunol 2011; 29: 415-445.Gregor M.F., Hotamisligil G.S. Inflammatory mechanisms in obesity. Ann Review Immunol 2011; 29: 415-445.Hirosumi J., Tuncman G., Chang L., Görgün C.Z., Uysal K.T., Maeda K., Karin M., Hotamisligil G.S. A central, role for JNK in obesity and insulin resistance. Nature 2002; 420: 6913: 333-336.Hirosumi J., Tuncman G., Chang L., Görgün C.Z., Uysal K.T., Maeda K., Karin M., Hotamisligil G.S. A central, role for JNK in obesity and insulin resistance. Nature 2002; 420: 6913: 333-336.Yuan M., Konstantopoulos N., Lee J., Hansen L., Li Z.W., ­Karin M., Shoelson S.E. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of IkkΒ. Science 2001; 293: 5535: 1673-1677.Yuan M., Konstantopoulos N., Lee J., Hansen L., Li Z.W., ­Karin M., Shoelson S.E. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of IkkΒ. Science 2001; 293: 5535: 1673-1677.Nakamura T., Furuhashi M., Li P., Tuncman G., Sonenberg N., Gorgun C.Z., Hotamisligil G.S. Double-stranded RNA-dependent protein kinase links pathogen sensing with stress and metabolic homeostasis. Cell 2010; 140: 3: 338-348.Nakamura T., Furuhashi M., Li P., Tuncman G., Sonenberg N., Gorgun C.Z., Hotamisligil G.S. Double-stranded RNA-dependent protein kinase links pathogen sensing with stress and metabolic homeostasis. Cell 2010; 140: 3: 338-348.Furuhashi M., Hotamisligil G.S. Fatty acid-binding proteins: role in metabolic diseases and potential as drug targets. Nature Rev Drug Dis 2008; 7: 6: 489-503.Furuhashi M., Hotamisligil G.S. Fatty acid-binding proteins: role in metabolic diseases and potential as drug targets. Nature Rev Drug Dis 2008; 7: 6: 489-503.Baxa C.A., Sha R.S., Buelt M.K., Smith A.J., Matarese V., Chinander L.L., Boundy K.L., Bernlohr D.A. Human adipocyte lipid-binding protein: purification of the protein and cloning of its complementary DNA. Biochemistry 1989; 28: 22: 8683-8690.Baxa C.A., Sha R.S., Buelt M.K., Smith A.J., Matarese V., Chinander L.L., Boundy K.L., Bernlohr D.A. Human adipocyte lipid-binding protein: purification of the protein and cloning of its complementary DNA. Biochemistry 1989; 28: 22: 8683-8690.Furuhashi M., Ishimura S., Ota H., Miura Т. Lipid сhaperones and мetabolic inflammation. Int J Inflam 2011; Article ID 642612.Furuhashi M., Ishimura S., Ota H., Miura Т. Lipid сhaperones and мetabolic inflammation. Int J Inflam 2011; Article ID 642612.Furuhashi M., Fucho R., Gorgun C. Z., Tuncman G., Cao H., Hotamisligil G.S. Adipocyte/macrophage fatty acid-binding proteins contribute to metabolic deterioration through actions in both macrophages and adipocytes in mice. J Clin Inv 2008; 118: 7: 2640-2650.Furuhashi M., Fucho R., Gorgun C. Z., Tuncman G., Cao H., Hotamisligil G.S. Adipocyte/macrophage fatty acid-binding proteins contribute to metabolic deterioration through actions in both macrophages and adipocytes in mice. J Clin Inv 2008; 118: 7: 2640-2650.Makowski L., Boord J.B., Maeda K., Babaev V.R., Uysal K.T., Morgan M.A., Parker R.A., Suttles J., Fazio S., Hotamisligil G.S., Linton M.F. Lack of macrophage fatty-acid-binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis. Nature Med 2001; 7: 6: 699-705.Makowski L., Boord J.B., Maeda K., Babaev V.R., Uysal K.T., Morgan M.A., Parker R.A., Suttles J., Fazio S., Hotamisligil G.S., Linton M.F. Lack of macrophage fatty-acid-binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis. Nature Med 2001; 7: 6: 699-705.Shum B.O., Mackay C.R., Gorgun C.Z., Frost M.J., Kumar R.K., Hotamisligil G.S., Rolph M.S. The adipocyte fatty acid-binding protein aP2 is required in allergic airway inflammation. J Clin Inv 2006; 116: 8: 2183-2192.Shum B.O., Mackay C.R., Gorgun C.Z., Frost M.J., Kumar R.K., Hotamisligil G.S., Rolph M.S. The adipocyte fatty acid-binding protein aP2 is required in allergic airway inflammation. J Clin Inv 2006; 116: 8: 2183-2192.Amri E.Z., Bertrand B., Ailhaud G., Grimaldi P. Regulationof adipose cell differentiation. I. Fatty acids are inducers of the aP2 gene expression. J Lipid Res 1991; 32: 9: 1449-1456.Amri E.Z., Bertrand B., Ailhaud G., Grimaldi P. Regulationof adipose cell differentiation. I. Fatty acids are inducers of the aP2 gene expression. J Lipid Res 1991; 32: 9: 1449-1456.Kletzien R.F., Foellmi L.A., Harris P.K., Wyse B.M., Clarke S.D. Adipocyte fatty acid-binding protein: regulation of gene expression in vivo and in vitro by an insulin-sensitizing agent. Mol Pharmacol 1992; 42: 4: 558-562.Kletzien R.F., Foellmi L.A., Harris P.K., Wyse B.M., Clarke S.D. Adipocyte fatty acid-binding protein: regulation of gene expression in vivo and in vitro by an insulin-sensitizing agent. Mol Pharmacol 1992; 42: 4: 558-562.Melki S.A., Abumrad N.A. Expression of the adipocyte fatty acid-binding protein in streptozotocin- diabetes: effects of insulin deficiency and supplementation. J Lipid Res 1993; 34: 9: 1527-1534.Melki S.A., Abumrad N.A. Expression of the adipocyte fatty acid-binding protein in streptozotocin- diabetes: effects of insulin deficiency and supplementation. J Lipid Res 1993; 34: 9: 1527-1534.Hui X., Li H., Zhou Z., Lam K.S., Xiao Y., Wu D., Ding K., Wang Y., Vanhoutte P.M., Xu A. Adipocyte fatty acid-binding protein modulates inflammatory responses in macrophages through a positive feedback loop involving c-Jun NH 2- terminal kinases and activator protein-1. J Biol Chem 2010; 285: 14: 10273-10280.Hui X., Li H., Zhou Z., Lam K.S., Xiao Y., Wu D., Ding K., Wang Y., Vanhoutte P.M., Xu A. Adipocyte fatty acid-binding protein modulates inflammatory responses in macrophages through a positive feedback loop involving c-Jun NH 2- terminal kinases and activator protein-1. J Biol Chem 2010; 285: 14: 10273-10280.Wang X.Q., Yang K., He Y.S., Lu L., Shen W.F. Receptor mediated elevation in FABP4 levels by advanced glycation end products induces cholesterol and triacylglycerol accumulation in THP-1 macrophages. Lipids 2011; 46: 6: 479-486.Wang X.Q., Yang K., He Y.S., Lu L., Shen W.F. Receptor mediated elevation in FABP4 levels by advanced glycation end products induces cholesterol and triacylglycerol accumulation in THP-1 macrophages. Lipids 2011; 46: 6: 479-486.Llaverias G., Penuelas S., Noe V., Vázquez-Carrera M., Sánchez R.M., Laguna J.C., Ciudad C.J., Alegret M. Atorvastatin reduces CD68, FABP4, and HBP expression in oxLDL-treated human macrophages. Biochem Biophys Res Commun 2004; 318: 1: 265-274.Llaverias G., Penuelas S., Noe V., Vázquez-Carrera M., Sánchez R.M., Laguna J.C., Ciudad C.J., Alegret M. Atorvastatin reduces CD68, FABP4, and HBP expression in oxLDL-treated human macrophages. Biochem Biophys Res Commun 2004; 318: 1: 265-274.Song J., Ren P., Zhang L., Wang X.L., Chen L., Shen Y.H. Metformin reduces lipid accumulation in macrophages by inhibiting FOXO1-mediated transcription of fatty acid binding protein 4. Biochem Biophys Res Commun 2010; 393: 1: 89-94.Song J., Ren P., Zhang L., Wang X.L., Chen L., Shen Y.H. Metformin reduces lipid accumulation in macrophages by inhibiting FOXO1-mediated transcription of fatty acid binding protein 4. Biochem Biophys Res Commun 2010; 393: 1: 89-94.Thompson B.R., Mazurkiewicz-Munoz A.M., Suttles J., Carter-Su C., Bernlohr D.A. Interaction of adipocyte fatty acid-binding protein (AFABP) and JAK2: AFABP/aP2as a regulator of JAK2 signaling. J Biol Chem 2009; 284: 20: 13473-13480.Thompson B.R., Mazurkiewicz-Munoz A.M., Suttles J., Carter-Su C., Bernlohr D.A. Interaction of adipocyte fatty acid-binding protein (AFABP) and JAK2: AFABP/aP2as a regulator of JAK2 signaling. J Biol Chem 2009; 284: 20: 13473-13480.Shen W.J., Sridhar K., Bernlohr D.A., Kraemer F.B. Interaction of rat hormone-sensitive lipase with adipocytelipid-binding protein. Proceedings. Nat Acad Sci (USA) 1999; 6:10:5528-5532.Shen W.J., Sridhar K., Bernlohr D.A., Kraemer F.B. Interaction of rat hormone-sensitive lipase with adipocytelipid-binding protein. Proceedings. Nat Acad Sci (USA) 1999; 6:10:5528-5532.Coe N.R., Simpson M.A., Bernlohr D.A. Targeted disruption of the adipocyte lipid-binding protein (aP2protein) gene impairs fat cell lipolysis and increases cellular fatty acid levels. J Lipid Res 1999; 40: 5: 967-972.Coe N.R., Simpson M.A., Bernlohr D.A. Targeted disruption of the adipocyte lipid-binding protein (aP2protein) gene impairs fat cell lipolysis and increases cellular fatty acid levels. J Lipid Res 1999; 40: 5: 967-972.Hotamisligil G.S., Johnson R.S., Distel R.J., Ellis R., Papaioannou V.E., Spiegelman B.M. Uncoupling of obesity from insulin resistance through a targeted mutation in aP2, the adipocyte fatty acid binding protein. Science 1996; 274: 5291: 1377-1379.Hotamisligil G.S., Johnson R.S., Distel R.J., Ellis R., Papaioannou V.E., Spiegelman B.M. Uncoupling of obesity from insulin resistance through a targeted mutation in aP2, the adipocyte fatty acid binding protein. Science 1996; 274: 5291: 1377-1379.Uysal K.T., Scheja L., Wiesbrock S.M., Bonner-Weir S., Hotamisligil G.S. Improved glucose and lipid metabolism in genetically obese mice lacking aP2. Endocrinology 2000; 141: 9: 3388-3396.Uysal K.T., Scheja L., Wiesbrock S.M., Bonner-Weir S., Hotamisligil G.S. Improved glucose and lipid metabolism in genetically obese mice lacking aP2. Endocrinology 2000; 141: 9: 3388-3396.Boord J.B., Maeda K., Makowski L., Babaev V.R., Fazio S., Linton M.F., Hotamisligil G.S. Combined adipocyte-macrophage fatty acid-binding protein deficiency improves metabolism, atherosclerosis, and survival in apolipoprotein E-deficient mice. Circulation 2004; 110: 11: 1492-1498.Boord J.B., Maeda K., Makowski L., Babaev V.R., Fazio S., Linton M.F., Hotamisligil G.S. Combined adipocyte-macrophage fatty acid-binding protein deficiency improves metabolism, atherosclerosis, and survival in apolipoprotein E-deficient mice. Circulation 2004; 110: 11: 1492-1498.Maeda K., Uysal K.T., Makowski L., Görgün C.Z., Atsumi G., Parker R.A., Brüning J., Hertzel A.V., Bernlohr D.A., Hotamisligil G.S. Role of the fatty acid binding protein mal1 in obesity and insulin resistance. Diabetes 2003; 52: 2: 300-307.Maeda K., Uysal K.T., Makowski L., Görgün C.Z., Atsumi G., Parker R.A., Brüning J., Hertzel A.V., Bernlohr D.A., Hotamisligil G.S. Role of the fatty acid binding protein mal1 in obesity and insulin resistance. Diabetes 2003; 52: 2: 300-307.Hertzel A.V., Benars-Eiden A., Bernlohr D.A. Increased lipolysis in transgenic animals overexpressing the epithelial fatty acid binding protein in adipose cells. J Lipid Res 2002; 43: 12: 2105-2111.Hertzel A.V., Benars-Eiden A., Bernlohr D.A. Increased lipolysis in transgenic animals overexpressing the epithelial fatty acid binding protein in adipose cells. J Lipid Res 2002; 43: 12: 2105-2111.Agardh H.E., Folkersen L., Ekstrand J., Marcus D., Swedenborg J., Hedin U., Gabrielsen A., Paulsson-Berne G. Expression of fatty acid-binding protein 4/aP2 is correlated with plaque instability in carotid atherosclerosis. J Int Med 2011; 269: 2: 200-210.Agardh H.E., Folkersen L., Ekstrand J., Marcus D., Swedenborg J., Hedin U., Gabrielsen A., Paulsson-Berne G. Expression of fatty acid-binding protein 4/aP2 is correlated with plaque instability in carotid atherosclerosis. J Int Med 2011; 269: 2: 200-210.Maeda K., Cao H., Kono K., Gorgun C.Z., Furuhashi M., Uysal K.T., Cao Q., Atsumi G., Malone H., Krishnan B., Minokoshi Y., Kahn B.B., Parker R.A., Hotamisligil G.S. Adipocyte/macrophagefatty acid binding proteins control integrated metabolic responses in obesity and diabetes. Cell Metab 2005; 1: 2: 107-119.Maeda K., Cao H., Kono K., Gorgun C.Z., Furuhashi M., Uysal K.T., Cao Q., Atsumi G., Malone H., Krishnan B., Minokoshi Y., Kahn B.B., Parker R.A., Hotamisligil G.S. Adipocyte/macrophagefatty acid binding proteins control integrated metabolic responses in obesity and diabetes. Cell Metab 2005; 1: 2: 107-119.Cao H., Maeda K., Gorgun C.Z., Kim H.J., Park S.Y., Shulman G.I., Kim J.K., Hotamisligil G.S. Regulation of metabolic responses by adipocyte/macrophage fatty acid binding proteins in leptin-deficient mice. Diabetes 2006; 55: 7: 1915-1922.Cao H., Maeda K., Gorgun C.Z., Kim H.J., Park S.Y., Shulman G.I., Kim J.K., Hotamisligil G.S. Regulation of metabolic responses by adipocyte/macrophage fatty acid binding proteins in leptin-deficient mice. Diabetes 2006; 55: 7: 1915-1922.Cao H., Gerhold K., Mayers J.R., Wiest M.M., Watkins S.M., Hotamisligil G.S. Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism. Cell 2008; 134: 6: 933-944.Cao H., Gerhold K., Mayers J.R., Wiest M.M., Watkins S.M., Hotamisligil G.S. Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism. Cell 2008; 134: 6: 933-944.Coleman S.L., Park Y.-K., Lee J.-Y. Unsaturated fatty acids repress the expression of adipocyte fatty acid binding protein via the modulation of histone deacetylation in RAW264.7 macrophages. Eur J Clin Nutr 2011; 50: 5: 323-330.Coleman S.L., Park Y.-K., Lee J.-Y. Unsaturated fatty acids repress the expression of adipocyte fatty acid binding protein via the modulation of histone deacetylation in RAW264.7 macrophages. Eur J Clin Nutr 2011; 50: 5: 323-330.Stefan N., Kantartzis K., Celebi N., Staiger H., Machann J., Schick F., Cegan A., Elcnerova M., Schleicher E., Fritsche A., Häring H.U. Circulating palmitoleate strongly and independently predicts insulin sensitivity in humans. Diabet Care 2010; 33: 2: 405-407.Stefan N., Kantartzis K., Celebi N., Staiger H., Machann J., Schick F., Cegan A., Elcnerova M., Schleicher E., Fritsche A., Häring H.U. Circulating palmitoleate strongly and independently predicts insulin sensitivity in humans. Diabet Care 2010; 33: 2: 405-407.Elmasri H., Karaaslan C., Teper Y., Ghelfi E., Weng M., Ince T.A., 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: 11: 3865-3873.Elmasri H., Karaaslan C., Teper Y., Ghelfi E., Weng M., Ince T.A., 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: 11: 3865-3873.Nourani M.R., Owada Y., Kitanaka N., Sakagami H., Hoshi H., Iwasa H., Spener F., Kondo H. Occurrence of immunoreactivity for adipocyte-type fatty acid binding protein in degenerating granulosa cells in atretic antral follicles of mouse ovary. J Mol Histol 2005; 36: 8-9: 491-497.Nourani M.R., Owada Y., Kitanaka N., Sakagami H., Hoshi H., Iwasa H., Spener F., Kondo H. Occurrence of immunoreactivity for adipocyte-type fatty acid binding protein in degenerating granulosa cells in atretic antral follicles of mouse ovary. J Mol Histol 2005; 36: 8-9: 491-497.Han Q., Yeung S.C., Ip M.S.M., Mak J.C.W. Effects of intermittent hypoxia on A-/E-FABP expression in human aortic endothelial cells. Int J Cardiol 2010; 145: 2: 396-398, 2010.Han Q., Yeung S.C., Ip M.S.M., Mak J.C.W. Effects of intermittent hypoxia on A-/E-FABP expression in human aortic endothelial cells. Int J Cardiol 2010; 145: 2: 396-398, 2010.Bagheri R., Qasim A.N., Mehta N.N., Terembula K., Kapoor S., Braunstein S., Schutta M., Iqbal N., Lehrke M., Reilly M.P. Relation of plasma fatty acid binding proteins 4 and 5 with the metabolic syndrome, inflammation and coronary calcium in patients with type-2 diabetes mellitus. Am J Cardiol 2010; 106: 8: 1118-1123.Bagheri R., Qasim A.N., Mehta N.N., Terembula K., Kapoor S., Braunstein S., Schutta M., Iqbal N., Lehrke M., Reilly M.P. Relation of plasma fatty acid binding proteins 4 and 5 with the metabolic syndrome, inflammation and coronary calcium in patients with type-2 diabetes mellitus. Am J Cardiol 2010; 106: 8: 1118-1123.Holm S., Ueland T., Dahl T.B., Michelsen A.E., Skjelland M., Russell D., Nymo S.H., Krohg-Sørensen K., Clausen O.P., Atar D., Januzzi J.L., Aukrust P., Jensen J.K., Halvorsen B. Fatty Acid binding protein 4 is associated with carotid atherosclerosis and outcome in patients with acute ischemic stroke. PLoS One 2011; 6: 12: 28785.Holm S., Ueland T., Dahl T.B., Michelsen A.E., Skjelland M., Russell D., Nymo S.H., Krohg-Sørensen K., Clausen O.P., Atar D., Januzzi J.L., Aukrust P., Jensen J.K., Halvorsen B. Fatty Acid binding protein 4 is associated with carotid atherosclerosis and outcome in patients with acute ischemic stroke. PLoS One 2011; 6: 12: 28785.Tso A.W., Lam T.K., Xu A., Yiu K.H., Tse H.F., Li L.S., Law L.S., Cheung B.M., Cheung R.T., Lam K.S. Serum adipocyte fatty acid-binding protein associated with ischemic stroke and early death. Neurology 2011; 76: 23: 1968-1975.Tso A.W., Lam T.K., Xu A., Yiu K.H., Tse H.F., Li L.S., Law L.S., Cheung B.M., Cheung R.T., Lam K.S. Serum adipocyte fatty acid-binding protein associated with ischemic stroke and early death. Neurology 2011; 76: 23: 1968-1975.Peeters W., de Kleijn D.P., Vink A., van de Weg S., Schoneveld A.H., Sze S.K., van der Spek P.J., de Vries J.P., Moll F.L., Pasterkamp G. Adipocyte fatty acid binding protein in atherosclerotic plaques is associated with local vulnerability and is predictive for the occurrence of adverse cardiovascular events. Eur Heart J 2011; 32: 14: 1758-1768.Peeters W., de Kleijn D.P., Vink A., van de Weg S., Schoneveld A.H., Sze S.K., van der Spek P.J., de Vries J.P., Moll F.L., Pasterkamp G. Adipocyte fatty acid binding protein in atherosclerotic plaques is associated with local vulnerability and is predictive for the occurrence of adverse cardiovascular events. Eur Heart J 2011; 32: 14: 1758-1768.Yoo H.J., Kim S., Park M.S., Choi H.Y., Yang S.J., Seo J.A., Kim S.G., Kim N.H., Baik S.H., Choi D.S., Choi K.M. Serum adipocyte Fatty Acid-Binding Protein is associated independently with vascular inflammation: Analysis with 18F-Fluorodeoxyglucose positron emission tomography. J Clin Endocrinol Metab 2011; 96: 3: E488-E492.Yoo H.J., Kim S., Park M.S., Choi H.Y., Yang S.J., Seo J.A., Kim S.G., Kim N.H., Baik S.H., Choi D.S., Choi K.M. Serum adipocyte Fatty Acid-Binding Protein is associated independently with vascular inflammation: Analysis with 18F-Fluorodeoxyglucose positron emission tomography. J Clin Endocrinol Metab 2011; 96: 3: E488-E492.Furuhashi M., Ishimura S., Ota H., Hayashi M., Nishitani T., Tanaka M., Yoshida H., Shimamoto K., Hotamisligil G.S., Miura T. Serum fatty acid-binding protein 4 is a predictor of cardiovascular events in end-stage renal disease. PLoS One 2011; 6: 11: e27356.Furuhashi M., Ishimura S., Ota H., Hayashi M., Nishitani T., Tanaka M., Yoshida H., Shimamoto K., Hotamisligil G.S., Miura T. Serum fatty acid-binding protein 4 is a predictor of cardiovascular events in end-stage renal disease. PLoS One 2011; 6: 11: e27356.Doi M, Miyoshi T, Hirohata S, et al. Association of increased plasma adipocyte fatty acid-binding protein with coronary artery disease in non-elderly men. Cardiovasc Diabet 2011; 10: 44. doi: 10.1186/1475-2840-10-44Doi M, Miyoshi T, Hirohata S, et al. Association of increased plasma adipocyte fatty acid-binding protein with coronary artery disease in non-elderly men. Cardiovasc Diabet 2011; 10: 44. doi: 10.1186/1475-2840-10-44Stejskal D., Karpisek M. Adipocyte fatty acid binding protein in a Caucasian population: a new marker of metabolic syndrome? Eur J Clin Invest 2006; 36: 621-625.Stejskal D., Karpisek M. Adipocyte fatty acid binding protein in a Caucasian population: a new marker of metabolic syndrome? Eur J Clin Invest 2006; 36: 621-625.Cabré A., Lázaro I., Girona J., Manzanares J.M., Marimón F., Plana N., Heras M., Masana L. Fatty acid binding protein 4 is increased in metabolic syndrome and with thiazolidinedione treatment in diabetic patients. Atherosclerosis 2007; 195: e150-e158.Cabré A., Lázaro I., Girona J., Manzanares J.M., Marimón F., Plana N., Heras M., Masana L. Fatty acid binding protein 4 is increased in metabolic syndrome and with thiazolidinedione treatment in diabetic patients. Atherosclerosis 2007; 195: e150-e158.Tso A.W., Xu A., Sham P.C., Wat N.M., Wang Y., Fong C.H., Cheung B.M., Janus E.D., Lam K.S. Serum adipocyte fatty acid binding protein as a new biomarker predicting the development of type 2 diabetes: a 10-year prospective study in a Chinese cohort. Diabet Care 2007; 30: 2667-2672.Tso A.W., Xu A., Sham P.C., Wat N.M., Wang Y., Fong C.H., Cheung B.M., Janus E.D., Lam K.S. Serum adipocyte fatty acid binding protein as a new biomarker predicting the development of type 2 diabetes: a 10-year prospective study in a Chinese cohort. Diabet Care 2007; 30: 2667-2672.Aimin Xu, Annette W.K. Tso, Bernard M.Y. Cheung. Circulating Adipocyte Fatty Acid Binding Protein levels predict the development of the metabolic syndrome: a 5-year prospective study. Circulation 2007; 115: 1537-1543.Aimin Xu, Annette W.K. Tso, Bernard M.Y. Cheung. Circulating Adipocyte Fatty Acid Binding Protein levels predict the development of the metabolic syndrome: a 5-year prospective study. Circulation 2007; 115: 1537-1543.Terra X., Quintero Y., Auguet T. Porras J.A., Hernández M., Sabench F., Aguilar C., Luna A.M., Del Castillo D., Richart C. FABP 4 is associated with inflammatory markers and metabolic syndrome in morbidly obese women. Eur J Endocrinol 2011; 164: 4: 539-547.Terra X., Quintero Y., Auguet T. Porras J.A., Hernández M., Sabench F., Aguilar C., Luna A.M., Del Castillo D., Richart C. FABP 4 is associated with inflammatory markers and metabolic syndrome in morbidly obese women. Eur J Endocrinol 2011; 164: 4: 539-547.Xu A., Wang Y., Xu J.Y., Stejskal D., Stejskal D., Tam S., Zhang J., Wat N.M., Wong W.K., Lam K.S. Adipocyte fatty acid-binding protein is a plasma biomarker closely associated with obesity and metabolic syndrome. Clin Chem 2006; 52: 405-413.Xu A., Wang Y., Xu J.Y., Stejskal D., Stejskal D., Tam S., Zhang J., Wat N.M., Wong W.K., Lam K.S. Adipocyte fatty acid-binding protein is a plasma biomarker closely associated with obesity and metabolic syndrome. Clin Chem 2006; 52: 405-413.Yeung D.C., Xu A., Cheung C.W., Wat N.M., Yau M.H., Fong C.H., Chau M.T., Lam K.S. Serum adipocyte fatty acid-binding protein levels were independently associated with carotid atherosclerosis. Arterioscler Thromb Vasc Biol 2007; 27: 1796-1802.Yeung D.C., Xu A., Cheung C.W., Wat N.M., Yau M.H., Fong C.H., Chau M.T., Lam K.S. Serum adipocyte fatty acid-binding protein levels were independently associated with carotid atherosclerosis. Arterioscler Thromb Vasc Biol 2007; 27: 1796-1802.Scifres C.M., Catov J.M., Simhan H. Maternal serum Fatty Acid Binding Protein 4 (FABP4) and the development of preeclampsia. J Clin Endocrinol Metab 2012; 97: 3: E349-E356.Scifres C.M., Catov J.M., Simhan H. Maternal serum Fatty Acid Binding Protein 4 (FABP4) and the development of preeclampsia. J Clin Endocrinol Metab 2012; 97: 3: E349-E356.Scifres C.M., Chen B., Nelson M., Sadovsky Y. Fatty Acid Binding Protein 4 Regulates Intracellular Lipid Accumulation in Human Trophoblasts. J Clin Endocrinol Metab 2011; 96: 7: E1083-E1091.Scifres C.M., Chen B., Nelson M., Sadovsky Y. Fatty Acid Binding Protein 4 Regulates Intracellular Lipid Accumulation in Human Trophoblasts. J Clin Endocrinol Metab 2011; 96: 7: E1083-E1091.Tuncman G., Erbay E., Hom X., De Vivo I., Campos H., Rimm E.B., Hotamisligil G.S. A genetic variant at the fatty acid-binding protein aP2 locus reduces the risk for hypertriglyceridemia, type 2 diabetes, and cardiovascular disease. Proc Natl Acad Sci USA 2006; 103: 18: 6970-6975.Tuncman G., Erbay E., Hom X., De Vivo I., Campos H., Rimm E.B., Hotamisligil G.S. A genetic variant at the fatty acid-binding protein aP2 locus reduces the risk for hypertriglyceridemia, type 2 diabetes, and cardiovascular disease. Proc Natl Acad Sci USA 2006; 103: 18: 6970-6975.Chan K., Song Y., Hsu Y-H. You N.C., Tinker L., Liu S. Common Genetic Variants in Fatty Acid-Binding Protein-4 (FABP4) and Clinical Diabetes Risk in the Women's Health Initiative Observational study. Obesity (Silver Spring) 2010; 18: 9: 1812-1820.Chan K., Song Y., Hsu Y-H. You N.C., Tinker L., Liu S. Common Genetic Variants in Fatty Acid-Binding Protein-4 (FABP4) and Clinical Diabetes Risk in the Women's Health Initiative Observational study. Obesity (Silver Spring) 2010; 18: 9: 1812-1820.Mansego M.L., Martínez F., Martínez-Larrad M.T., Zabena C., Rojo G., Morcillo S., Soriguer F., Martín-Escudero J.C., Serrano-Ríos M., Redon J., Chaves F.J. Common variants of the liver Fatty Acid binding protein gene influence the risk of type 2 diabetes and insulin resistance in spanish population. PLoS One 2012; 7: 3: e31853.Mansego M.L., Martínez F., Martínez-Larrad M.T., Zabena C., Rojo G., Morcillo S., Soriguer F., Martín-Escudero J.C., Serrano-Ríos M., Redon J., Chaves F.J. Common variants of the liver Fatty Acid binding protein gene influence the risk of type 2 diabetes and insulin resistance in spanish population. PLoS One 2012; 7: 3: e31853.Reinehr T., Stoffel-Wagner B., Roth C.L. Adipocyte fatty acid-binding protein in obese children before and after weight loss. Metabolism 2007; 56: 12: 1735-1741.Reinehr T., Stoffel-Wagner B., Roth C.L. Adipocyte fatty acid-binding protein in obese children before and after weight loss. Metabolism 2007; 56: 12: 1735-1741.Yun K.E., Kim S.M., Choi K.M., Park H.S. Association between adipocyte fatty acid-binding protein levels and childhood obesity in Korean children. Metabolism 2009; 58: 6.Yun K.E., Kim S.M., Choi K.M., Park H.S. Association between adipocyte fatty acid-binding protein levels and childhood obesity in Korean children. Metabolism 2009; 58: 6.Khalyfa A., Bhushan B., Hegazi M., Kim J., Kheirandish-Gozal L., Bhattacharjee R., Capdevila O.S., Gozal D. Fatty-acid binding protein 4 gene variants and childhood obesity: potential implications for insulin sensitivity and CRP levels. Lipids Health Dis 2010; 9: 18.Khalyfa A., Bhushan B., Hegazi M., Kim J., Kheirandish-Gozal L., Bhattacharjee R., Capdevila O.S., Gozal D. Fatty-acid binding protein 4 gene variants and childhood obesity: potential implications for insulin sensitivity and CRP levels. Lipids Health Dis 2010; 9: 18.Bhushan B., Khalyfa A., Spruyt K., Kheirandish-Gozal L., Capdevila O.S., Bhattacharjee R., Kim J., Keating B., Hakonarson H., Gozal D. Fatty-acid binding protein 4 gene polymorphisms and plasma levels in children with obstructive sleep apnea. Sleep Med 2011; 12: 7: 666-671.Bhushan B., Khalyfa A., Spruyt K., Kheirandish-Gozal L., Capdevila O.S., Bhattacharjee R., Kim J., Keating B., Hakonarson H., Gozal D. Fatty-acid binding protein 4 gene polymorphisms and plasma levels in children with obstructive sleep apnea. Sleep Med 2011; 12: 7: 666-671.Choi K. Serum adipocyte fatty acid-binding protein, retinol-binding protein 4, and adiponectin concentrations in relation to the development of the metabolic syndrome in Korean boys: a 3-years prospective cohort study. Am J Clin Nutr 2011; 93: 1: 19-26.Choi K. Serum adipocyte fatty acid-binding protein, retinol-binding protein 4, and adiponectin concentrations in relation to the development of the metabolic syndrome in Korean boys: a 3-years prospective cohort study. Am J Clin Nutr 2011; 93: 1: 19-26.Liang Y., Chan C.P., Cheung K.Y., Cautherley G.W., Glatz J.F., Renneberg R., Zhu J. CardioDetect rapid test for the diagnosis of early acute myocardial infarction. J Immunoas Immunochem 2011; 32: 4: 342-352.Liang Y., Chan C.P., Cheung K.Y., Cautherley G.W., Glatz J.F., Renneberg R., Zhu J. CardioDetect rapid test for the diagnosis of early acute myocardial infarction. J Immunoas Immunochem 2011; 32: 4: 342-352.Furuhashi M., Tuncman G., Gorgun C.Z., Makowski L., Atsumi G., Vaillancourt E., Kono K., Babaev V.R., Fazio S., Linton M.F., Sulsky R., Robl J.A., Parker R.A., Hotamisligil G.S. Treatment of diabetes and atherosclerosis by inhibiting fatty-acid binding protein aP2. Nature 2007; 447: 7147: 959-965.Furuhashi M., Tuncman G., Gorgun C.Z., Makowski L., Atsumi G., Vaillancourt E., Kono K., Babaev V.R., Fazio S., Linton M.F., Sulsky R., Robl J.A., Parker R.A., Hotamisligil G.S. Treatment of diabetes and atherosclerosis by inhibiting fatty-acid binding protein aP2. Nature 2007; 447: 7147: 959-965.Chawla A., Nguyen K.D., Sharon Goh Y.P. Macrophage-mediated inflammation in metabolic disease. Nature 2011; 11: 738-749.Chawla A., Nguyen K.D., Sharon Goh Y.P. Macrophage-mediated inflammation in metabolic disease. Nature 2011; 11: 738-749.

The authors declare that there are no conflicts of interest present.