Abstract
Background:
ATP-binding cassette transporters (ABCA1, ABCG1) and scavenger receptor class B type I (SR-BI) are the three most important cellular cholesterol transporters/receptor in regulating cholesterol efflux. We have investigated whether the expression of these transporters/receptor is altered in overweight and obese patients, and the potential association with the circulating adipokines.
Methods:
Adiponectin, leptin and resistin were assayed in two groups of healthy controls, overweight and obese patients. The expression of ABCA1, ABCG1 and SR-BI in monocytes was measured. Cholesterol efflux from monocyte-derived macrophages was also determined.
Results:
Circulating adiponectin was decreased, whereas leptin and resistin were increased in overweight and obese patients compared with healthy controls. ABCA1 expression was significantly decreased in overweight and obese patients (P<0.01), whereas the levels of ABCG1 and SR-BI were comparable between the two groups. Adiponectin was correlated with ABCA1 (r=0.44, P<0.001), but not with ABCG1 and SR-BI. No associations between leptin, resistin and the expression of ABCA1, ABCG1 and SR-BI were found. Cholesterol efflux from monocyte-derived macrophages to apolipoprotein AI or to autologous serum was significantly impaired in overweight and obese patients, which were correlated with ABCA1 expression (r=0.47, P<0.001; r=0.43, P<0.001, respectively).
Conclusion:
The expression of ABCA1 in monocytes is reduced in overweight and obese patients, and the reduction in ABCA1 is associated with the impairment of cholesterol efflux from monocyte-derived macrophages.
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References
Lewis GF, Rader DJ . New insights into the regulation of HDL metabolism and reverse cholesterol transport. Circ Res 2005; 96: 1221–1232.
Jessup W, Gelissen IC, Gaus K, Kritharides L . Roles of ATP binding cassette transporters A1 and G1, scavenger receptor BI and membrane lipid domains in cholesterol export from macrophages. Curr Opin Lipidol 2006; 17: 247–257.
Van Eck M, Pennings M, Hoekstra M, Out R, Van Berkel TJ . Scavenger receptor BI and ATP-binding cassette transporter A1 in reverse cholesterol transport and atherosclerosis. Curr Opin Lipidol 2005; 16: 307–315.
Wang X, Collins HL, Ranalletta M, Fuki IV, Billheimer JT, Rothblat GH et al. Macrophage ABCA1 and ABCG1, but not SR-BI, promote macrophage reverse cholesterol transport in vivo. J Clin Invest 2007; 117: 2216–2224.
Tian L, Jia L, Mingde F, Tian Y, Xu Y, Tian H et al. Alterations of high density lipoprotein subclasses in obese subjects. Lipids 2006; 41: 789–796.
Sasahara T, Nestel P, Fidge N, Sviridov D . Cholesterol transport between cells and high density lipoprotein subfractions from obese and lean subjects. J Lipid Res 1998; 39: 544–554.
Shige H, Nestel P, Sviridov D, Noakes M, Clifton P . Effect of weight reduction on the distribution of apolipoprotein A-I in high-density lipoprotein subfractions in obese non-insulin-dependent diabetic subjects. Metabolism 2000; 49: 1453–1459.
Altinova AE, Toruner F, Bukan N, Yasar DG, Akturk M, Cakir N et al. Decreased plasma adiponectin is associated with insulin resistance and HDL cholesterol in overweight subjects. Endocr J 2007; 54: 221–226.
Matsuura F, Oku H, Koseki M, Sandoval JC, Yuasa-Kawase M, Tsubakio-Yamamoto K et al. Adiponectin accelerates reverse cholesterol transport by increasing high density lipoprotein assembly in the liver. Biochem Biophys Res Commun 2007; 358: 1091–1095.
Oku H, Matsuura F, Koseki M, Sandoval JC, Yuasa-Kawase M, Tsubakio-Yamamoto K et al. Adiponectin deficiency suppresses ABCA1 expression and ApoA-I synthesis in the liver. FEBS Lett 2007; 581: 5029–5033.
Tian L, Luo N, Klein RL, Chung BH, Garvey WT, Fu Y . Adiponectin reduces lipid accumulation in macrophage foam cells. Atherosclerosis 2009; 202: 152–161.
Tsubakio-Yamamoto K, Matsuura F, Koseki M, Oku H, Sandoval JC, Inagaki M et al. Adiponectin prevents atherosclerosis by increasing cholesterol efflux from macrophages. Biochem Biophys Res Commun 2008; 375: 390–394.
Koh KK, Park SM, Quon MJ . Leptin and cardiovascular disease: response to therapeutic interventions. Circulation 2008; 117: 3238–3249.
Gómez-Ambrosi J, Frühbeck G . Evidence for the involvement of resistin in inflammation and cardiovascular disease. Curr Diabetes Rev 2005; 1: 227–234.
Rae C, Robertson SA, Taylor JM, Graham A . Resistin induces lipolysis and re-esterification of triacylglycerol stores, and increases cholesteryl ester deposition, in human macrophages. FEBS Lett 2007; 581: 4877–4883.
Cabrero A, Cubero M, Llaverías G, Alegret M, Sánchez R, Laguna JC et al. Leptin down-regulates peroxisome proliferator-activated receptor gamma (PPAR-gamma) mRNA levels in primary human monocyte-derived macrophages. Mol Cell Biochem 2005; 275: 173–179.
Yu Z, Lin X, Haas JD, Franco OH, Rennie KL, Li H et al. Nutrition and Health of Ageing Population in China Study Research Group. Obesity related metabolic abnormalities: distribution and geographic differences among middle-aged and older Chinese populations. Prev Med 2009; 48: 272–278.
Hattori H, Kujiraoka T, Egashira T, Saito E, Fujioka T, Takahashi S et al. Association of coronary heart disease with pre-beta-HDL concentrations in Japanese men. Clin Chem 2004; 50: 589–595.
Zhou H, Tan KC, Shiu SW, Wong Y . Determinants of leukocyte adenosine triphosphate-binding cassette transporter G1 gene expression in type 2 diabetes mellitus. Metabolism 2008; 57: 1135–1140.
Gianturco SH, Ramprasad MP, Lin AH, Song R, Bradley WA . Cellular binding site and membrane binding proteins for triglyceride-rich lipoproteins in human monocyte-macrophages and THP-1 monocytic cells. J Lipid Res 1994; 35: 1674–1687.
Chen M, Li W, Wang N, Zhu Y, Wang X . ROS and NF-kappaB but not LXR mediate IL-1beta signaling for the downregulation of ATP-binding cassette transporter A1. Am J Physiol Cell Physiol 2007; 292: C1493–C1501.
Isoda K, Folco EJ, Shimizu K, Libby P . AGE-BSA decreases ABCG1 expression and reduces macrophage cholesterol efflux to HDL. Atherosclerosis 2007; 192: 298–304.
Langmann T, Klucken J, Reil M, Liebisch G, Luciani MF, Chimini G et al. Molecular cloning of the human ATP-binding cassette transporter 1 (hABC1): evidence for sterol-dependent regulation in macrophages. Biochem Biophys Res Commun 1999; 257: 29–33.
Klucken J, Buchler C, Orso E, Kaminski WE, Porsch-Ozcurumez M, Liebisch G et al. ABCG1 (ABC8), the human homolog of the Drosophila white gene, is a regulator of macrophage cholesterol and phospholipid transport. Proc Natl Acad Sci USA 2000; 97: 817–822.
Han J, Nicholson AC, Zhou X, Feng J, Gotto Jr AM, Hajjar DP . Oxidized low density lipoprotein decreases macrophage expression of scavenger receptor B-I. J Biol Chem 2001; 276: 16567–16572.
Acknowledgements
We thank the following colleagues at The First Affiliated Hospital, College of Medicine, Zhejiang University for their generous help in completing this study: Dr Haiyang Xie for his technical assistant, Dr Lihong Qiu for recruiting volunteers and the colleagues from the Department of Clinical Biochemistry for performing the clinical biochemical measurements.
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Xu, M., Zhou, H., Wang, J. et al. The expression of ATP-binding cassette transporter A1 in Chinese overweight and obese patients. Int J Obes 33, 851–856 (2009). https://doi.org/10.1038/ijo.2009.120
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DOI: https://doi.org/10.1038/ijo.2009.120
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