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Erschienen in: Diabetologia 1/2013

01.01.2013 | Review

Adipocyte fatty acid binding protein: a novel adipokine involved in the pathogenesis of metabolic and vascular disease?

verfasst von: S. Kralisch, M. Fasshauer

Erschienen in: Diabetologia | Ausgabe 1/2013

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Abstract

Adipocyte fatty acid binding protein (AFABP, also known as aP2 and FABP4) has recently been introduced as a novel fat-derived circulating protein. AFABP serum concentrations are positively correlated with markers of the metabolic syndrome and vascular disease in various cross-sectional and interventional studies. Furthermore, a small set of prospective studies indicates that high AFABP serum levels at baseline predict the risk for metabolic and vascular morbidity and mortality. Studies in Afabp (also known as Fabp4) knockout mice and AFABP inhibitor-treated animals suggest that total AFABP promotes insulin resistance, hypertriacylglycerolaemia and atherosclerosis by ligand/ligand delivery, as well as ligand-independent mechanisms. In contrast, the pathophysiological significance of circulating AFABP and the mechanisms leading to its release remain to be established. The current review summarises recent findings on the regulation and potential role of AFABP in metabolic and vascular disease.
Literatur
2.
Zurück zum Zitat Fruebis J, Tsao TS, Javorschi S et al (2001) Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci USA 98:2005–2010PubMedCrossRef Fruebis J, Tsao TS, Javorschi S et al (2001) Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci USA 98:2005–2010PubMedCrossRef
3.
Zurück zum Zitat Baxa CA, Sha RS, Buelt MK et al (1989) Human adipocyte lipid-binding protein—purification of the protein and cloning of its complementary-DNA. Biochemistry 28:8683–8690PubMedCrossRef Baxa CA, Sha RS, Buelt MK et al (1989) Human adipocyte lipid-binding protein—purification of the protein and cloning of its complementary-DNA. Biochemistry 28:8683–8690PubMedCrossRef
4.
Zurück zum Zitat Fu YC, Luo NL, Lopes-Virella MF, Garvey WT (2002) The adipocyte lipid binding protein (ALBP/aP2) gene facilitates foam cell formation in human THP-1 macrophages. Atherosclerosis 165:259–269PubMedCrossRef Fu YC, Luo NL, Lopes-Virella MF, Garvey WT (2002) The adipocyte lipid binding protein (ALBP/aP2) gene facilitates foam cell formation in human THP-1 macrophages. Atherosclerosis 165:259–269PubMedCrossRef
5.
Zurück zum Zitat Elmasri H, Karaaslan C, Teper Y et al (2009) Fatty acid binding protein 4 is a target of VEGF and a regulator of cell proliferation in endothelial cells. FASEB J 23:3865–3873PubMedCrossRef Elmasri H, Karaaslan C, Teper Y et al (2009) Fatty acid binding protein 4 is a target of VEGF and a regulator of cell proliferation in endothelial cells. FASEB J 23:3865–3873PubMedCrossRef
6.
Zurück zum Zitat Bernlohr DA, Angus CW, Lane MD, Bolanowski MA, Kelly TJ (1984) Expression of specific mRNAs during adipose differentiation: identification of an mRNA encoding a homologue of myelin P2 protein. Proc Natl Acad Sci USA 81:5468–5472PubMedCrossRef Bernlohr DA, Angus CW, Lane MD, Bolanowski MA, Kelly TJ (1984) Expression of specific mRNAs during adipose differentiation: identification of an mRNA encoding a homologue of myelin P2 protein. Proc Natl Acad Sci USA 81:5468–5472PubMedCrossRef
7.
Zurück zum Zitat Bernlohr DA, Bolanowski MA, Kelly TJ, Lane MD (1985) Evidence for an increase in transcription of specific mRNAs during differentiation of 3t3-l1 preadipocytes. J Biol Chem 260:5563–5567PubMed Bernlohr DA, Bolanowski MA, Kelly TJ, Lane MD (1985) Evidence for an increase in transcription of specific mRNAs during differentiation of 3t3-l1 preadipocytes. J Biol Chem 260:5563–5567PubMed
8.
Zurück zum Zitat Bernlohr DA, Doering TL, Kelly TJ, Lane MD (1985) Tissue specific expression of p422 protein, a putative lipid carrier, in mouse adipocytes. Biochem Biophys Res Commun 132:850–855PubMedCrossRef Bernlohr DA, Doering TL, Kelly TJ, Lane MD (1985) Tissue specific expression of p422 protein, a putative lipid carrier, in mouse adipocytes. Biochem Biophys Res Commun 132:850–855PubMedCrossRef
9.
Zurück zum Zitat Smith PJ, Wise LS, Berkowitz R, Wan C, Rubin CS (1988) Insulin-like growth factor-I is an essential regulator of the differentiation of 3T3-L1 adipocytes. J Biol Chem 263:9402–9408PubMed Smith PJ, Wise LS, Berkowitz R, Wan C, Rubin CS (1988) Insulin-like growth factor-I is an essential regulator of the differentiation of 3T3-L1 adipocytes. J Biol Chem 263:9402–9408PubMed
10.
Zurück zum Zitat Yang VW, Christy RJ, Cook JS, Kelly TJ, Lane MD (1989) Mechanism of regulation of the 422(Ap2) gene by CAMP during preadipocyte differentiation. Proc Natl Acad Sci USA 86:3629–3633PubMedCrossRef Yang VW, Christy RJ, Cook JS, Kelly TJ, Lane MD (1989) Mechanism of regulation of the 422(Ap2) gene by CAMP during preadipocyte differentiation. Proc Natl Acad Sci USA 86:3629–3633PubMedCrossRef
11.
Zurück zum Zitat Christy RJ, Yang VW, Ntambi JM et al (1989) Differentiation-induced gene expression in 3T3-L1 preadipocytes: CCAAT/enhancer binding protein interacts with and activates the promoters of two adipocyte-specific genes. Genes Dev 3:1323–1335PubMedCrossRef Christy RJ, Yang VW, Ntambi JM et al (1989) Differentiation-induced gene expression in 3T3-L1 preadipocytes: CCAAT/enhancer binding protein interacts with and activates the promoters of two adipocyte-specific genes. Genes Dev 3:1323–1335PubMedCrossRef
12.
Zurück zum Zitat Cabré A, Lázaro I, Girona J et al (2007) Fatty acid binding protein 4 is increased in metabolic syndrome and with thiazolidinedione treatment in diabetic patients. Atherosclerosis 195:e150–e158PubMedCrossRef Cabré A, Lázaro I, Girona J et al (2007) Fatty acid binding protein 4 is increased in metabolic syndrome and with thiazolidinedione treatment in diabetic patients. Atherosclerosis 195:e150–e158PubMedCrossRef
13.
Zurück zum Zitat Kletzien RF, Foellmi LA, Harris PKW, Wyse BM, Clarke SD (1992) Adipocyte fatty acid-binding protein: regulation of gene expression in vivo and in vitro by an insulin-sensitizing agent. Mol Pharmacol 42:558–562PubMed Kletzien RF, Foellmi LA, Harris PKW, Wyse BM, Clarke SD (1992) Adipocyte fatty acid-binding protein: regulation of gene expression in vivo and in vitro by an insulin-sensitizing agent. Mol Pharmacol 42:558–562PubMed
14.
Zurück zum Zitat Fisher RM, Eriksson P, Hoffstedt J et al (2001) Fatty acid binding protein expression in different adipose tissue depots from lean and obese individuals. Diabetologia 44:1268–1273PubMedCrossRef Fisher RM, Eriksson P, Hoffstedt J et al (2001) Fatty acid binding protein expression in different adipose tissue depots from lean and obese individuals. Diabetologia 44:1268–1273PubMedCrossRef
15.
Zurück zum Zitat Coe NR, Bernlohr DA (1998) Physiological properties and functions of intracellular fatty acid-binding proteins. Biochim Biophys Acta 1391:287–306PubMedCrossRef Coe NR, Bernlohr DA (1998) Physiological properties and functions of intracellular fatty acid-binding proteins. Biochim Biophys Acta 1391:287–306PubMedCrossRef
16.
Zurück zum Zitat Lalonde JM, Bernlohr DA, Banaszak LJ (1994) X-ray crystallographic structures of adipocyte lipid-binding protein complexed with palmitate and hexadecanesulfonic acid—properties of cavity binding-sites. Biochemistry 33:4885–4895PubMedCrossRef Lalonde JM, Bernlohr DA, Banaszak LJ (1994) X-ray crystallographic structures of adipocyte lipid-binding protein complexed with palmitate and hexadecanesulfonic acid—properties of cavity binding-sites. Biochemistry 33:4885–4895PubMedCrossRef
17.
Zurück zum Zitat Xu ZH, Bernlohr DA, Banaszak LJ (1993) The adipocyte lipid-binding protein at 1.6-a resolution—crystal-structures of the apoprotein and with bound saturated and unsaturated fatty-acids. J Biol Chem 268:7874–7884PubMed Xu ZH, Bernlohr DA, Banaszak LJ (1993) The adipocyte lipid-binding protein at 1.6-a resolution—crystal-structures of the apoprotein and with bound saturated and unsaturated fatty-acids. J Biol Chem 268:7874–7884PubMed
18.
Zurück zum Zitat Liou HL, Storch J (2001) Role of surface lysine residues of adipocyte fatty acid-binding protein in fatty acid transfer to phospholipid vesicles. Biochemistry 40:6475–6485PubMedCrossRef Liou HL, Storch J (2001) Role of surface lysine residues of adipocyte fatty acid-binding protein in fatty acid transfer to phospholipid vesicles. Biochemistry 40:6475–6485PubMedCrossRef
19.
Zurück zum Zitat Shen WJ, Liang Y, Hong R et al (2001) Characterization of the functional interaction of adipocyte lipid-binding protein with hormone-sensitive lipase. J Biol Chem 276:49443–49448PubMedCrossRef Shen WJ, Liang Y, Hong R et al (2001) Characterization of the functional interaction of adipocyte lipid-binding protein with hormone-sensitive lipase. J Biol Chem 276:49443–49448PubMedCrossRef
20.
Zurück zum Zitat Smith AJ, Thompson BR, Sanders MA, Bernlohr DA (2007) Interaction of the adipocyte fatty acid-binding protein with the hormone-sensitive lipase—regulation by fatty acids and phosphorylation. J Biol Chem 282:32424–32432PubMedCrossRef Smith AJ, Thompson BR, Sanders MA, Bernlohr DA (2007) Interaction of the adipocyte fatty acid-binding protein with the hormone-sensitive lipase—regulation by fatty acids and phosphorylation. J Biol Chem 282:32424–32432PubMedCrossRef
21.
Zurück zum Zitat Hertzel AV, Hellberg K, Reynolds JM et al (2009) Identification and characterization of a small molecule inhibitor of fatty acid binding proteins. J Med Chem 52:6024–6031PubMedCrossRef Hertzel AV, Hellberg K, Reynolds JM et al (2009) Identification and characterization of a small molecule inhibitor of fatty acid binding proteins. J Med Chem 52:6024–6031PubMedCrossRef
22.
Zurück zum Zitat Smith AJ, Sanders MA, Juhlmann BE, Hertzel AV, Bernlohr DA (2008) Mapping of the hormone-sensitive lipase binding site on the adipocyte fatty acid-binding protein (AFABP) identification of the charge quartet on the AFABP/aP2 helix-turn-helix domain. J Biol Chem 283:33536–33543PubMedCrossRef Smith AJ, Sanders MA, Juhlmann BE, Hertzel AV, Bernlohr DA (2008) Mapping of the hormone-sensitive lipase binding site on the adipocyte fatty acid-binding protein (AFABP) identification of the charge quartet on the AFABP/aP2 helix-turn-helix domain. J Biol Chem 283:33536–33543PubMedCrossRef
23.
Zurück zum Zitat Adida A, Spener F (2006) Adipocyte-type fatty acid-binding protein as inter-compartmental shuttle for peroxisome proliferator activated receptor γ agonists in cultured cell. Biochim Biophys Acta 1761:172–181PubMedCrossRef Adida A, Spener F (2006) Adipocyte-type fatty acid-binding protein as inter-compartmental shuttle for peroxisome proliferator activated receptor γ agonists in cultured cell. Biochim Biophys Acta 1761:172–181PubMedCrossRef
24.
Zurück zum Zitat Gillilan RE, Ayers SD, Noy N (2007) Structural basis for activation of fatty acid-binding protein 4. J Mol Biol 372:1246–1260PubMedCrossRef Gillilan RE, Ayers SD, Noy N (2007) Structural basis for activation of fatty acid-binding protein 4. J Mol Biol 372:1246–1260PubMedCrossRef
25.
Zurück zum Zitat Ayers SD, Nedrow KL, Gillilan RE, Noy N (2007) Continuous nucleocytoplasmic shuttling underlies transcriptional activation of PPAR gamma by FABP4. Biochemistry 46:6744–6752PubMedCrossRef Ayers SD, Nedrow KL, Gillilan RE, Noy N (2007) Continuous nucleocytoplasmic shuttling underlies transcriptional activation of PPAR gamma by FABP4. Biochemistry 46:6744–6752PubMedCrossRef
26.
Zurück zum Zitat Tan N-S, Shaw NS, Vinckenbosch N, Liu P, Yasmin R et al (2002) Selective cooperation between fatty acid binding proteins and peroxisome proliferator-activated receptors in regulating transcription. Mol Cell Biol 22:5114–5127PubMedCrossRef Tan N-S, Shaw NS, Vinckenbosch N, Liu P, Yasmin R et al (2002) Selective cooperation between fatty acid binding proteins and peroxisome proliferator-activated receptors in regulating transcription. Mol Cell Biol 22:5114–5127PubMedCrossRef
27.
Zurück zum Zitat Hotamisligil GS, Johnson RS, Distel RJ et al (1996) Uncoupling of obesity from insulin resistance through a targeted mutation in aP2, the adipocyte fatty acid binding protein. Science 274:1377–1379PubMedCrossRef Hotamisligil GS, Johnson RS, Distel RJ et al (1996) Uncoupling of obesity from insulin resistance through a targeted mutation in aP2, the adipocyte fatty acid binding protein. Science 274:1377–1379PubMedCrossRef
28.
Zurück zum Zitat Coe NR, Simpson MA, Bernlohr DA (1999) Targeted disruption of the adipocyte lipid-binding protein (aP2 protein) gene impairs fat cell lipolysis and increases cellular fatty acid levels. J Lipid Res 40:967–972PubMed Coe NR, Simpson MA, Bernlohr DA (1999) Targeted disruption of the adipocyte lipid-binding protein (aP2 protein) gene impairs fat cell lipolysis and increases cellular fatty acid levels. J Lipid Res 40:967–972PubMed
29.
Zurück zum Zitat Shaughnessy S, Smith ER, Kodukula S, Storch J, Fried SK (2000) Adipocyte metabolism in adipocyte fatty acid binding protein knockout (aP2(−/−)) mice after short-term high-fat feeding—functional compensation by the keritinocyte fatty acid binding protein. Diabetes 49:904–911PubMedCrossRef Shaughnessy S, Smith ER, Kodukula S, Storch J, Fried SK (2000) Adipocyte metabolism in adipocyte fatty acid binding protein knockout (aP2(−/−)) mice after short-term high-fat feeding—functional compensation by the keritinocyte fatty acid binding protein. Diabetes 49:904–911PubMedCrossRef
30.
Zurück zum Zitat Maeda K, Cao H, Kono K, Gorgun CZ, Furuhashi M et al (2005) Adipocyte/macrophage fatty acid binding proteins control integrated metabolic responses in obesity and diabetes. Cell Metab 1:107–119PubMedCrossRef Maeda K, Cao H, Kono K, Gorgun CZ, Furuhashi M et al (2005) Adipocyte/macrophage fatty acid binding proteins control integrated metabolic responses in obesity and diabetes. Cell Metab 1:107–119PubMedCrossRef
31.
Zurück zum Zitat Uysal KT, Scheja L, Wiesbrock SM, Bonner-Weir S, Hotamisligil GS (2000) Improved glucose and lipid metabolism in genetically obese mice lacking aP2. Endocrinology 141:3388–3396PubMedCrossRef Uysal KT, Scheja L, Wiesbrock SM, Bonner-Weir S, Hotamisligil GS (2000) Improved glucose and lipid metabolism in genetically obese mice lacking aP2. Endocrinology 141:3388–3396PubMedCrossRef
32.
Zurück zum Zitat Baar RA, Dingfelder CS, Smith LA et al (2005) Investigation of in vivo fatty acid metabolism in AFABP/aP2(−/−) mice. Am J Physiol Endocrinol Metab 288:E187–E193PubMedCrossRef Baar RA, Dingfelder CS, Smith LA et al (2005) Investigation of in vivo fatty acid metabolism in AFABP/aP2(−/−) mice. Am J Physiol Endocrinol Metab 288:E187–E193PubMedCrossRef
33.
Zurück zum Zitat Cao H, Maeda K, Gorgun CZ et al (2006) Regulation of metabolic responses by adipocyte/macrophage fatty acid-binding proteins in leptin-deficient mice. Diabetes 55:1915–1922PubMedCrossRef Cao H, Maeda K, Gorgun CZ et al (2006) Regulation of metabolic responses by adipocyte/macrophage fatty acid-binding proteins in leptin-deficient mice. Diabetes 55:1915–1922PubMedCrossRef
34.
Zurück zum Zitat Scheja L, Makowski L, Uysal KT et al (1999) Altered insulin secretion associated with reduced lipolytic efficiency in aP2−/− mice. Diabetes 48:1987–1994PubMedCrossRef Scheja L, Makowski L, Uysal KT et al (1999) Altered insulin secretion associated with reduced lipolytic efficiency in aP2−/− mice. Diabetes 48:1987–1994PubMedCrossRef
35.
Zurück zum Zitat Furuhashi M, Tuncman G, Gorgun CZ et al (2007) Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2. Nature 447:959–965PubMedCrossRef Furuhashi M, Tuncman G, Gorgun CZ et al (2007) Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2. Nature 447:959–965PubMedCrossRef
36.
Zurück zum Zitat Lan H, Cheng CC, Kowalski TJ et al (2011) Small-molecule inhibitors of FABP4/5 ameliorate dyslipidaemia but not insulin resistance in mice with diet-induced obesity. J Lipid Res 52:646–656PubMedCrossRef Lan H, Cheng CC, Kowalski TJ et al (2011) Small-molecule inhibitors of FABP4/5 ameliorate dyslipidaemia but not insulin resistance in mice with diet-induced obesity. J Lipid Res 52:646–656PubMedCrossRef
37.
Zurück zum Zitat Yang R, Castriota G, Chen Y et al (2011) RNAi-mediated germline knockdown of FABP4 increases body weight but does not improve the deranged nutrient metabolism of diet-induced obese mice. Int J Obes (Lond) 35:217–225CrossRef Yang R, Castriota G, Chen Y et al (2011) RNAi-mediated germline knockdown of FABP4 increases body weight but does not improve the deranged nutrient metabolism of diet-induced obese mice. Int J Obes (Lond) 35:217–225CrossRef
38.
Zurück zum Zitat Makowski L, Boord JB, Maeda K et al (2001) Lack of macrophage fatty-acid-binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis. Nat Med 7:699–705PubMedCrossRef Makowski L, Boord JB, Maeda K et al (2001) Lack of macrophage fatty-acid-binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis. Nat Med 7:699–705PubMedCrossRef
39.
Zurück zum Zitat Boord JB, Maeda K, Makowski L et al (2002) Adipocyte fatty acid-binding protein, aP2, alters late atherosclerotic lesion formation in severe hypercholesterolemia. Arterioscler Thromb Vasc Biol 22:1686–1691PubMedCrossRef Boord JB, Maeda K, Makowski L et al (2002) Adipocyte fatty acid-binding protein, aP2, alters late atherosclerotic lesion formation in severe hypercholesterolemia. Arterioscler Thromb Vasc Biol 22:1686–1691PubMedCrossRef
40.
Zurück zum Zitat Boord JB, Maeda K, Makowski L et al (2004) Combined adipocyte-macrophage fatty acid-binding protein deficiency improves metabolism, atherosclerosis, and survival in apolipoprotein E-deficient mice. Circulation 110:1492–1498PubMedCrossRef Boord JB, Maeda K, Makowski L et al (2004) Combined adipocyte-macrophage fatty acid-binding protein deficiency improves metabolism, atherosclerosis, and survival in apolipoprotein E-deficient mice. Circulation 110:1492–1498PubMedCrossRef
41.
Zurück zum Zitat Lee MYK, Li HY, Xiao Y et al (2011) Chronic administration of BMS309403 improves endothelial function in apolipoprotein E-deficient mice and in cultured human endothelial cells. Br J Pharmacol 162:1564–1576PubMedCrossRef Lee MYK, Li HY, Xiao Y et al (2011) Chronic administration of BMS309403 improves endothelial function in apolipoprotein E-deficient mice and in cultured human endothelial cells. Br J Pharmacol 162:1564–1576PubMedCrossRef
42.
Zurück zum Zitat Tuncman G, Erbay E, Hom X et al (2006) 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 103:6970–6975PubMedCrossRef Tuncman G, Erbay E, Hom X et al (2006) 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 103:6970–6975PubMedCrossRef
43.
Zurück zum Zitat Chan KHK, Song YQ, Hsu YH et al (2010) Common genetic variants in fatty acid-binding protein-4 (FABP4) and clinical diabetes risk in the Women’s Health Initiative observational study. Obesity 18:1812–1820PubMedCrossRef Chan KHK, Song YQ, Hsu YH et al (2010) Common genetic variants in fatty acid-binding protein-4 (FABP4) and clinical diabetes risk in the Women’s Health Initiative observational study. Obesity 18:1812–1820PubMedCrossRef
44.
Zurück zum Zitat Makowski L, Brittingham KC, Reynolds JM, Suttles J, Hotamisligil GS (2005) The fatty acid-binding protein, aP2, coordinates macrophage cholesterol trafficking and inflammatory activity. Macrophage expression of aP2 impacts peroxisome proliferator-activated receptor gamma and IkappaB kinase activities. J Biol Chem 280:12888–12895PubMedCrossRef Makowski L, Brittingham KC, Reynolds JM, Suttles J, Hotamisligil GS (2005) The fatty acid-binding protein, aP2, coordinates macrophage cholesterol trafficking and inflammatory activity. Macrophage expression of aP2 impacts peroxisome proliferator-activated receptor gamma and IkappaB kinase activities. J Biol Chem 280:12888–12895PubMedCrossRef
45.
Zurück zum Zitat Shum BO, Mackay CR, Gorgun CZ et al (2006) The adipocyte fatty acid-binding protein aP2 is required in allergic airway inflammation. J Clin Invest 116:2183–2192PubMedCrossRef Shum BO, Mackay CR, Gorgun CZ et al (2006) The adipocyte fatty acid-binding protein aP2 is required in allergic airway inflammation. J Clin Invest 116:2183–2192PubMedCrossRef
46.
Zurück zum Zitat Reynolds JM, Liu Q, Brittingham KC et al (2007) Deficiency of fatty acid-binding proteins in mice confers protection from development of experimental autoimmune encephalomyelitis. J Immunol 179:313–321PubMed Reynolds JM, Liu Q, Brittingham KC et al (2007) Deficiency of fatty acid-binding proteins in mice confers protection from development of experimental autoimmune encephalomyelitis. J Immunol 179:313–321PubMed
47.
Zurück zum Zitat Kazemi MR, McDonald CM, Shigenaga JK, Grunfeld C, Feingold KR (2005) Adipocyte fatty acid-binding protein expression and lipid accumulation are increased during activation of murine macrophages by toll-like receptor agonists. Arterioscler Thromb Vasc Biol 25:1220–1224PubMedCrossRef Kazemi MR, McDonald CM, Shigenaga JK, Grunfeld C, Feingold KR (2005) Adipocyte fatty acid-binding protein expression and lipid accumulation are increased during activation of murine macrophages by toll-like receptor agonists. Arterioscler Thromb Vasc Biol 25:1220–1224PubMedCrossRef
48.
Zurück zum Zitat Shi H, Kokoeva MV, Inouye K et al (2006) TLR4 links innate immunity and fatty acid–induced insulin resistance. J Clin Invest 116:3015–3025PubMedCrossRef Shi H, Kokoeva MV, Inouye K et al (2006) TLR4 links innate immunity and fatty acid–induced insulin resistance. J Clin Invest 116:3015–3025PubMedCrossRef
49.
Zurück zum Zitat Hui X, Li H, Zhou Z et al (2010) Adipocyte fatty acid-binding protein modulates inflammatory responses in macrophages through a positive feedback loop involving c-Jun NH2-terminal kinases and activator protein-1. J Biol Chem 285:10273–10280PubMedCrossRef Hui X, Li H, Zhou Z et al (2010) Adipocyte fatty acid-binding protein modulates inflammatory responses in macrophages through a positive feedback loop involving c-Jun NH2-terminal kinases and activator protein-1. J Biol Chem 285:10273–10280PubMedCrossRef
50.
Zurück zum Zitat Erbay E, Babaev VR, Mayers JR et al (2009) Reducing endoplasmic reticulum stress through a macrophage lipid chaperone alleviates atherosclerosis. Nat Med 15:1383–1391PubMedCrossRef Erbay E, Babaev VR, Mayers JR et al (2009) Reducing endoplasmic reticulum stress through a macrophage lipid chaperone alleviates atherosclerosis. Nat Med 15:1383–1391PubMedCrossRef
51.
Zurück zum Zitat Fu YC, Luo LH, Luo NL, Garvey WT (2006) Lipid metabolism mediated by adipocyte lipid binding protein (ALBP/aP2) gene expression in human THP-1 macrophages. Atherosclerosis 188:102–111PubMedCrossRef Fu YC, Luo LH, Luo NL, Garvey WT (2006) Lipid metabolism mediated by adipocyte lipid binding protein (ALBP/aP2) gene expression in human THP-1 macrophages. Atherosclerosis 188:102–111PubMedCrossRef
52.
Zurück zum Zitat Wang XQ, Yang K, He YS, Lu L, Shen WF (2011) Receptor mediated elevation in FABP4 levels by advanced glycation end products induces cholesterol and triacylglycerol accumulation in THP-1 Macrophages. Lipids 46:479–486PubMedCrossRef Wang XQ, Yang K, He YS, Lu L, Shen WF (2011) Receptor mediated elevation in FABP4 levels by advanced glycation end products induces cholesterol and triacylglycerol accumulation in THP-1 Macrophages. Lipids 46:479–486PubMedCrossRef
53.
Zurück zum Zitat Saksi J, Nuotio K, Sonninen R et al (2011) Gene expression differences between stroke-associated and asymptomatic carotid plaques. J Mol Med 89:1015–1026PubMedCrossRef Saksi J, Nuotio K, Sonninen R et al (2011) Gene expression differences between stroke-associated and asymptomatic carotid plaques. J Mol Med 89:1015–1026PubMedCrossRef
54.
Zurück zum Zitat Holm S, Ueland T, Dahl TB et al (2011) Fatty acid binding protein 4 is associated with carotid atherosclerosis and outcome in patients with acute ischemic stroke. PLoS One 6:e28785PubMedCrossRef Holm S, Ueland T, Dahl TB et al (2011) Fatty acid binding protein 4 is associated with carotid atherosclerosis and outcome in patients with acute ischemic stroke. PLoS One 6:e28785PubMedCrossRef
55.
Zurück zum Zitat Agardh HE, Folkersen L, Ekstrand J et al (2011) Expression of fatty acid-binding protein 4/aP2 is correlated with plaque instability in carotid atherosclerosis. J Int Med 269:200–210CrossRef Agardh HE, Folkersen L, Ekstrand J et al (2011) Expression of fatty acid-binding protein 4/aP2 is correlated with plaque instability in carotid atherosclerosis. J Int Med 269:200–210CrossRef
56.
Zurück zum Zitat Peeters W, de Kleijn DPV, Vink A et al (2011) 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 32:1758–1768PubMedCrossRef Peeters W, de Kleijn DPV, Vink A et al (2011) 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 32:1758–1768PubMedCrossRef
57.
Zurück zum Zitat Llaverias G, Noé V, Peñuelas S et al (2004) Atorvastatin reduces CD68, FABP4, and HBP expression in oxLDL-treated human macrophages. Biochem Biophys Res Commun 318:265–274PubMedCrossRef Llaverias G, Noé V, Peñuelas S et al (2004) Atorvastatin reduces CD68, FABP4, and HBP expression in oxLDL-treated human macrophages. Biochem Biophys Res Commun 318:265–274PubMedCrossRef
58.
Zurück zum Zitat Elmasri H, Ghelfi E, Yu C et al (2012) Endothelial cell-fatty acid binding protein 4 promotes angiogenesis: role of stem cell factor/c-kit pathway. Angiogenesis 15:457–468PubMedCrossRef Elmasri H, Ghelfi E, Yu C et al (2012) Endothelial cell-fatty acid binding protein 4 promotes angiogenesis: role of stem cell factor/c-kit pathway. Angiogenesis 15:457–468PubMedCrossRef
59.
Zurück zum Zitat Xu A, Wang Y, Xu JY et al (2006) Adipocyte fatty acid-binding protein is a plasma biomarker closely associated with obesity and metabolic syndrome. Clin Chem 52:405–413PubMedCrossRef Xu A, Wang Y, Xu JY et al (2006) Adipocyte fatty acid-binding protein is a plasma biomarker closely associated with obesity and metabolic syndrome. Clin Chem 52:405–413PubMedCrossRef
60.
Zurück zum Zitat Veerkamp JH, Maatman RG (1995) Cytoplasmic fatty acid-binding proteins: their structure and genes. Prog Lipid Res 34:17–52PubMedCrossRef Veerkamp JH, Maatman RG (1995) Cytoplasmic fatty acid-binding proteins: their structure and genes. Prog Lipid Res 34:17–52PubMedCrossRef
61.
Zurück zum Zitat Reese-Wagoner A, Thompson J, Banaszak L (1999) Structural properties of the adipocyte lipid binding protein. Biochim Biophys Acta 1441:106–116PubMedCrossRef Reese-Wagoner A, Thompson J, Banaszak L (1999) Structural properties of the adipocyte lipid binding protein. Biochim Biophys Acta 1441:106–116PubMedCrossRef
62.
Zurück zum Zitat Radisky DC, Stallings-Mann M, Hirai Y, Bissell MJ (2009) Single proteins might have dual but related functions in intracellular and extracellular microenvironments. Nat Rev Mol Cell Biol 10:228–234PubMedCrossRef Radisky DC, Stallings-Mann M, Hirai Y, Bissell MJ (2009) Single proteins might have dual but related functions in intracellular and extracellular microenvironments. Nat Rev Mol Cell Biol 10:228–234PubMedCrossRef
63.
Zurück zum Zitat Mohan SK, Rani SG, Yu C (2010) The heterohexameric complex structure, a component in the non-classical pathway for fibroblast growth factor 1 (FGF1) secretion. J Biol Chem 285:15464–15475PubMedCrossRef Mohan SK, Rani SG, Yu C (2010) The heterohexameric complex structure, a component in the non-classical pathway for fibroblast growth factor 1 (FGF1) secretion. J Biol Chem 285:15464–15475PubMedCrossRef
64.
Zurück zum Zitat Aoki N, Jin-no S, Nakagawa Y et al (2007) Identification and characterization of microvesicles secreted by 3T3-L1 adipocytes: redox- and hormone-dependent induction of milk fat globule-epidermal growth factor 8-associated microvesicles. Endocrinology 148:3850–3862PubMedCrossRef Aoki N, Jin-no S, Nakagawa Y et al (2007) Identification and characterization of microvesicles secreted by 3T3-L1 adipocytes: redox- and hormone-dependent induction of milk fat globule-epidermal growth factor 8-associated microvesicles. Endocrinology 148:3850–3862PubMedCrossRef
65.
Zurück zum Zitat Lamounier-Zepter V, Look C, Alvarez J et al (2009) Adipocyte fatty acid-binding protein suppresses cardiomyocyte contraction: a new link between obesity and heart disease. Circ Res 105:326–334PubMedCrossRef Lamounier-Zepter V, Look C, Alvarez J et al (2009) Adipocyte fatty acid-binding protein suppresses cardiomyocyte contraction: a new link between obesity and heart disease. Circ Res 105:326–334PubMedCrossRef
66.
Zurück zum Zitat Stejskal D, Karpisek M (2006) Adipocyte fatty acid binding protein in a Caucasian population: a new marker of metabolic syndrome? Eur J Clin Invest 36:621–625PubMedCrossRef Stejskal D, Karpisek M (2006) Adipocyte fatty acid binding protein in a Caucasian population: a new marker of metabolic syndrome? Eur J Clin Invest 36:621–625PubMedCrossRef
67.
Zurück zum Zitat Coll B, Cabre A, Alonso-Villaverde C et al (2008) The fatty acid binding protein-4 (FABP4) is a strong biomarker of metabolic syndrome and lipodystrophy in HIV-infected patients. Atherosclerosis 199:147–153PubMedCrossRef Coll B, Cabre A, Alonso-Villaverde C et al (2008) The fatty acid binding protein-4 (FABP4) is a strong biomarker of metabolic syndrome and lipodystrophy in HIV-infected patients. Atherosclerosis 199:147–153PubMedCrossRef
68.
Zurück zum Zitat Cabre A, Lazaro I, Cofan M et al (2010) FABP4 plasma levels are increased in familial combined hyperlipidemia. J Lipid Res 51:1173–1178PubMedCrossRef Cabre A, Lazaro I, Cofan M et al (2010) FABP4 plasma levels are increased in familial combined hyperlipidemia. J Lipid Res 51:1173–1178PubMedCrossRef
69.
Zurück zum Zitat Milner KL, van der Poorten D, Xu A et al (2009) Adipocyte fatty acid binding protein levels relate to inflammation and fibrosis in nonalcoholic fatty liver disease. Hepatology 49:1926–1934PubMedCrossRef Milner KL, van der Poorten D, Xu A et al (2009) Adipocyte fatty acid binding protein levels relate to inflammation and fibrosis in nonalcoholic fatty liver disease. Hepatology 49:1926–1934PubMedCrossRef
70.
Zurück zum Zitat Yun KE, Kim SM, Choi KM, Park HS (2009) Association between adipocyte fatty acid-binding protein levels and childhood obesity in Korean children. Metabolism 58:798–802PubMedCrossRef Yun KE, Kim SM, Choi KM, Park HS (2009) Association between adipocyte fatty acid-binding protein levels and childhood obesity in Korean children. Metabolism 58:798–802PubMedCrossRef
71.
Zurück zum Zitat Tonjes A, Kralisch S, Lossner U et al (2012) Metabolic and genetic predictors of circulating adipocyte fatty acid-binding protein. Int J Obes 36:766–773CrossRef Tonjes A, Kralisch S, Lossner U et al (2012) Metabolic and genetic predictors of circulating adipocyte fatty acid-binding protein. Int J Obes 36:766–773CrossRef
72.
Zurück zum Zitat Cabre A, Lazaro I, Girona J et al (2008) Plasma fatty acid binding protein 4 is associated with atherogenic dyslipidemia in diabetes. J Lipid Res 49:1746–1751PubMedCrossRef Cabre A, Lazaro I, Girona J et al (2008) Plasma fatty acid binding protein 4 is associated with atherogenic dyslipidemia in diabetes. J Lipid Res 49:1746–1751PubMedCrossRef
73.
Zurück zum Zitat Hsu BG, Chen YC, Lee RP et al (2010) Fasting serum level of fatty-acid-binding protein 4 positively correlates with metabolic syndrome in patients with coronary artery disease. Circ J 74:327–331PubMedCrossRef Hsu BG, Chen YC, Lee RP et al (2010) Fasting serum level of fatty-acid-binding protein 4 positively correlates with metabolic syndrome in patients with coronary artery disease. Circ J 74:327–331PubMedCrossRef
74.
Zurück zum Zitat Yeung DC, Xu A, Cheung CW et al (2007) Serum adipocyte fatty acid-binding protein levels were independently associated with carotid atherosclerosis. Arterioscler Thromb Vasc Biol 27:1796–1802PubMedCrossRef Yeung DC, Xu A, Cheung CW et al (2007) Serum adipocyte fatty acid-binding protein levels were independently associated with carotid atherosclerosis. Arterioscler Thromb Vasc Biol 27:1796–1802PubMedCrossRef
75.
Zurück zum Zitat Rhee EJ, Lee WY, Park CY et al (2009) The association of serum adipocyte fatty acid-binding protein with coronary artery disease in Korean adults. Eur J Endocrinol 160:165–172PubMedCrossRef Rhee EJ, Lee WY, Park CY et al (2009) The association of serum adipocyte fatty acid-binding protein with coronary artery disease in Korean adults. Eur J Endocrinol 160:165–172PubMedCrossRef
76.
Zurück zum Zitat Doi M, Miyoshi T, Hirohata S et al (2011) Association of increased plasma adipocyte fatty acid-binding protein with coronary artery disease in non-elderly men. Cardiovasc Diabetol 10:44 Doi M, Miyoshi T, Hirohata S et al (2011) Association of increased plasma adipocyte fatty acid-binding protein with coronary artery disease in non-elderly men. Cardiovasc Diabetol 10:44
77.
Zurück zum Zitat Miyoshi T, Onoue G, Hirohata A et al (2010) Serum adipocyte fatty acid-binding protein is independently associated with coronary atherosclerotic burden measured by intravascular ultrasound. Atherosclerosis 211:164–169PubMedCrossRef Miyoshi T, Onoue G, Hirohata A et al (2010) Serum adipocyte fatty acid-binding protein is independently associated with coronary atherosclerotic burden measured by intravascular ultrasound. Atherosclerosis 211:164–169PubMedCrossRef
78.
Zurück zum Zitat Bao YQ, Lu ZG, Zhou M et al (2011) Serum levels of adipocyte fatty acid-binding protein are associated with the severity of coronary artery disease in chinese women. PLoS One 6:e19115PubMedCrossRef Bao YQ, Lu ZG, Zhou M et al (2011) Serum levels of adipocyte fatty acid-binding protein are associated with the severity of coronary artery disease in chinese women. PLoS One 6:e19115PubMedCrossRef
79.
Zurück zum Zitat Pala L, Monami M, Ciani S et al (2012) Adipokines as possible new predictors of cardiovascular diseases: a case control study. J Nutr Metab 2012:1–5CrossRef Pala L, Monami M, Ciani S et al (2012) Adipokines as possible new predictors of cardiovascular diseases: a case control study. J Nutr Metab 2012:1–5CrossRef
80.
Zurück zum Zitat Yoo HJ, Kim S, Park MS et al (2011) Serum adipocyte fatty acid-binding protein is associated independently with vascular inflammation: analysis with (18)F-fluorodeoxyglucose positron emission tomography. J Clin Endocrinol Metab 96:E488–E492PubMedCrossRef Yoo HJ, Kim S, Park MS et al (2011) Serum adipocyte fatty acid-binding protein is associated independently with vascular inflammation: analysis with (18)F-fluorodeoxyglucose positron emission tomography. J Clin Endocrinol Metab 96:E488–E492PubMedCrossRef
81.
Zurück zum Zitat Choi KM, Kim TN, Yoo HJ et al (2009) Effect of exercise training on A-FABP, lipocalin-2 and RBP4 levels in obese women. Clin Endocrinol 70:569–574CrossRef Choi KM, Kim TN, Yoo HJ et al (2009) Effect of exercise training on A-FABP, lipocalin-2 and RBP4 levels in obese women. Clin Endocrinol 70:569–574CrossRef
82.
Zurück zum Zitat Simon I, Escote X, Vilarrasa N et al (2009) Adipocyte fatty acid-binding protein as a determinant of insulin sensitivity in morbid-obese women. Obesity 17:1124–1128PubMed Simon I, Escote X, Vilarrasa N et al (2009) Adipocyte fatty acid-binding protein as a determinant of insulin sensitivity in morbid-obese women. Obesity 17:1124–1128PubMed
83.
Zurück zum Zitat Corripio R, Gonzalez-Clemente JM, Perez-Sanchez J et al (2010) Weight loss in prepubertal obese children is associated with a decrease in adipocyte fatty-acid-binding protein without changes in lipocalin-2: a 2-year longitudinal study. Eur J Endocrinol 163:887–893PubMedCrossRef Corripio R, Gonzalez-Clemente JM, Perez-Sanchez J et al (2010) Weight loss in prepubertal obese children is associated with a decrease in adipocyte fatty-acid-binding protein without changes in lipocalin-2: a 2-year longitudinal study. Eur J Endocrinol 163:887–893PubMedCrossRef
84.
Zurück zum Zitat Stejskal D, Karpisek M, Bronsky J (2008) Serum adipocyte-fatty acid binding protein discriminates patients with permanent and temporary body weight loss. J Clin Lab Ana 22:380–382CrossRef Stejskal D, Karpisek M, Bronsky J (2008) Serum adipocyte-fatty acid binding protein discriminates patients with permanent and temporary body weight loss. J Clin Lab Ana 22:380–382CrossRef
85.
Zurück zum Zitat Wu Y-W, Kao H-L, Huang C-L et al (2012) The effects of 3-month atorvastatin therapy on arterial inflammation, calcification, abdominal adipose tissue and circulating biomarkers. Eur J Nucl Med Mol Imaging 39:399–407PubMedCrossRef Wu Y-W, Kao H-L, Huang C-L et al (2012) The effects of 3-month atorvastatin therapy on arterial inflammation, calcification, abdominal adipose tissue and circulating biomarkers. Eur J Nucl Med Mol Imaging 39:399–407PubMedCrossRef
86.
Zurück zum Zitat Xu A, Tso AW, Cheung BM et al (2007) Circulating adipocyte-fatty acid binding protein levels predict the development of the metabolic syndrome: a 5-year prospective study. Circulation 115:1537–1543PubMedCrossRef Xu A, Tso AW, Cheung BM et al (2007) Circulating adipocyte-fatty acid binding protein levels predict the development of the metabolic syndrome: a 5-year prospective study. Circulation 115:1537–1543PubMedCrossRef
87.
Zurück zum Zitat Choi KM, Yannakoulia M, Park MS et al (2011) 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-y prospective cohort study. Am J Clin Nutr 93:19–26PubMedCrossRef Choi KM, Yannakoulia M, Park MS et al (2011) 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-y prospective cohort study. Am J Clin Nutr 93:19–26PubMedCrossRef
88.
Zurück zum Zitat Tso AW, Xu A, Sham PC et al (2007) 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. Diabetes Care 30:2667–2672PubMedCrossRef Tso AW, Xu A, Sham PC et al (2007) 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. Diabetes Care 30:2667–2672PubMedCrossRef
89.
Zurück zum Zitat Furuhashi M, Ishimura S, Ota H et al (2011) Serum fatty acid-binding protein 4 is a predictor of cardiovascular events in end-stage renal disease. PLoS One 6:e27356PubMedCrossRef Furuhashi M, Ishimura S, Ota H et al (2011) Serum fatty acid-binding protein 4 is a predictor of cardiovascular events in end-stage renal disease. PLoS One 6:e27356PubMedCrossRef
90.
Zurück zum Zitat Tso AWK, Lam TKY, Xu A et al (2011) Serum adipocyte fatty acid-binding protein associated with ischemic stroke and early death. Neurology 76:1968–1975PubMedCrossRef Tso AWK, Lam TKY, Xu A et al (2011) Serum adipocyte fatty acid-binding protein associated with ischemic stroke and early death. Neurology 76:1968–1975PubMedCrossRef
91.
Zurück zum Zitat von Eynatten M, Breitling LP, Roos M et al (2012) Circulating adipocyte fatty acid-binding protein levels and cardiovascular morbidity and mortality in patients with coronary heart disease. Arterioscler Thromb Vasc Biol 32:2327–2335CrossRef von Eynatten M, Breitling LP, Roos M et al (2012) Circulating adipocyte fatty acid-binding protein levels and cardiovascular morbidity and mortality in patients with coronary heart disease. Arterioscler Thromb Vasc Biol 32:2327–2335CrossRef
Metadaten
Titel
Adipocyte fatty acid binding protein: a novel adipokine involved in the pathogenesis of metabolic and vascular disease?
verfasst von
S. Kralisch
M. Fasshauer
Publikationsdatum
01.01.2013
Verlag
Springer-Verlag
Erschienen in
Diabetologia / Ausgabe 1/2013
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-012-2737-4

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