(Circulation. 2001;103:1057.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Adipocyte-Derived Plasma Protein, Adiponectin, Suppresses Lipid Accumulation and Class A Scavenger Receptor Expression in Human Monocyte-Derived Macrophages
From the Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan, and the Cellular Technology Institute (M.M., Y. Ohmoto), Otsuka Pharmaceutical Co., Ltd, Tokushima, Japan.
Correspondence to Noriyuki Ouchi, MD, Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan. E-mail ouchi{at}imed2.med.osaka-u.ac.jp
Background—Excessive lipid accumulation in macrophages plays an important role in the development of atherosclerosis. Recently, we discovered an adipocyte-specific plasma protein, adiponectin, that is decreased in patients with coronary artery disease. We previously demonstrated that adiponectin acts as a modulator for proinflammatory stimuli and inhibits monocyte adhesion to endothelial cells. The present study investigated the effects of adiponectin on lipid accumulation in human monocyte-derived macrophages.
Methods and Results—Human monocytes were differentiated into macrophages by incubation in human type AB serum for 7 days, and the effects of adiponectin were investigated at different time intervals. Treatment with physiological concentrations of adiponectin reduced intracellular cholesteryl ester content, as determined using the enzymatic, fluorometric method. The adiponectin-treated macrophages contained fewer lipid droplets stained by oil red O. Adiponectin suppressed the expression of the class A macrophage scavenger receptor (MSR) at both mRNA and protein levels by Northern and immunoblot analyses, respectively, without affecting the expression of CD36, which was quantified by flow cytometry. Adiponectin reduced the class A MSR promoter activity, as measured by luciferase reporter assay. Adiponectin treatment dose-dependently decreased class A MSR ligand binding and uptake activities. The mRNA level of lipoprotein lipase as a marker of macrophage differentiation was decreased by adiponectin treatment, but that of apolipoprotein E was not altered. Adiponectin was detected around macrophages in the human injured aorta by immunohistochemistry.
Conclusions—The adipocyte-derived plasma protein adiponectin suppressed macrophage-to-foam cell transformation, suggesting that adiponectin may act as a modulator for macrophage-to-foam cell transformation.
Key Words: atherosclerosis • macrophages • receptors • adiponectin
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K. Matsushita, H. Yatsuya, K. Tamakoshi, K. Wada, R. Otsuka, S. Takefuji, K. Sugiura, T. Kondo, T. Murohara, and H. Toyoshima Comparison of Circulating Adiponectin and Proinflammatory Markers Regarding Their Association With Metabolic Syndrome in Japanese Men Arterioscler Thromb Vasc Biol, April 1, 2006; 26(4): 871 - 876. [Abstract] [Full Text] [PDF]
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C. Kobashi, M. Urakaze, M. Kishida, E. Kibayashi, H. Kobayashi, S. Kihara, T. Funahashi, M. Takata, R. Temaru, A. Sato, et al. Adiponectin Inhibits Endothelial Synthesis of Interleukin-8 Circ. Res., December 9, 2005; 97(12): 1245 - 1252. [Abstract] [Full Text] [PDF]
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A. Singhal, N. Jamieson, M. Fewtrell, J. Deanfield, A. Lucas, and N. Sattar Adiponectin Predicts Insulin Resistance But Not Endothelial Function in Young, Healthy Adolescents J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4615 - 4621. [Abstract] [Full Text] [PDF]
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S. Pilz, R. Horejsi, R. Moller, G. Almer, H. Scharnagl, T. Stojakovic, R. Dimitrova, G. Weihrauch, M. Borkenstein, W. Maerz, et al. Early Atherosclerosis in Obese Juveniles Is Associated with Low Serum Levels of Adiponectin J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4792 - 4796. [Abstract] [Full Text] [PDF]
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Y. Fu, N. Luo, R. L. Klein, and W. T. Garvey Adiponectin promotes adipocyte differentiation, insulin sensitivity, and lipid accumulation J. Lipid Res., July 1, 2005; 46(7): 1369 - 1379. [Abstract] [Full Text] [PDF]
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A. Xu, K. W. Chan, R. L. C. Hoo, Y. Wang, K. C. B. Tan, J. Zhang, B. Chen, M. C. Lam, C. Tse, G. J. S. Cooper, et al. Testosterone Selectively Reduces the High Molecular Weight Form of Adiponectin by Inhibiting Its Secretion from Adipocytes J. Biol. Chem., May 6, 2005; 280(18): 18073 - 18080. [Abstract] [Full Text] [PDF]
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Y. Wang, K. S. L. Lam, J. Y. Xu, G. Lu, L. Y. Xu, G. J. S. Cooper, and A. Xu Adiponectin Inhibits Cell Proliferation by Interacting with Several Growth Factors in an Oligomerization-dependent Manner J. Biol. Chem., May 6, 2005; 280(18): 18341 - 18347. [Abstract] [Full Text] [PDF]
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T. Kadowaki and T. Yamauchi Adiponectin and Adiponectin Receptors Endocr. Rev., May 1, 2005; 26(3): 439 - 451. [Abstract] [Full Text] [PDF]
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D. C. W. Lau, B. Dhillon, H. Yan, P. E. Szmitko, and S. Verma Adipokines: molecular links between obesity and atheroslcerosis Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2031 - H2041. [Abstract] [Full Text] [PDF]
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T. Pischon, C. J Girman, N. Rifai, G. S Hotamisligil, and E. B Rimm Association between dietary factors and plasma adiponectin concentrations in men Am. J. Clinical Nutrition, April 1, 2005; 81(4): 780 - 786. [Abstract] [Full Text] [PDF]
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M.-P. Chen, J. C.-R. Tsai, F.-M. Chung, S.-S. Yang, L.-L. Hsing, S.-J. Shin, and Y.-J. Lee Hypoadiponectinemia Is Associated With Ischemic Cerebrovascular Disease Arterioscler Thromb Vasc Biol, April 1, 2005; 25(4): 821 - 826. [Abstract] [Full Text] [PDF]
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M. I. Yilmaz, A. Sonmez, S. Kilic, T. Celik, N. Bingol, M. Pinar, T. Mumcuoglu, and M. Ozata The association of plasma adiponectin levels with hypertensive retinopathy Eur. J. Endocrinol., February 1, 2005; 152(2): 233 - 240. [Abstract] [Full Text] [PDF]
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M.-T. Berthier, A. Houde, M. Cote, A.-M. Paradis, P. Mauriege, J. Bergeron, D. Gaudet, J.-P. Despres, and M.-C. Vohl Impact of adiponectin gene polymorphisms on plasma lipoprotein and adiponectin concentrations of viscerally obese men J. Lipid Res., February 1, 2005; 46(2): 237 - 244. [Abstract] [Full Text] [PDF]
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M. B. Schulze, I. Shai, E. B. Rimm, T. Li, N. Rifai, and F. B. Hu Adiponectin and Future Coronary Heart Disease Events Among Men With Type 2 Diabetes Diabetes, February 1, 2005; 54(2): 534 - 539. [Abstract] [Full Text] [PDF]
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H. Waki, T. Yamauchi, J. Kamon, S. Kita, Y. Ito, Y. Hada, S. Uchida, A. Tsuchida, S. Takekawa, and T. Kadowaki Generation of Globular Fragment of Adiponectin by Leukocyte Elastase Secreted by Monocytic Cell Line THP-1 Endocrinology, February 1, 2005; 146(2): 790 - 796. [Abstract] [Full Text] [PDF]
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S Kaser, A Moschen, A Cayon, A Kaser, J Crespo, F Pons-Romero, C F Ebenbichler, J R Patsch, and H Tilg Adiponectin and its receptors in non-alcoholic steatohepatitis Gut, January 1, 2005; 54(1): 117 - 121. [Abstract] [Full Text] [PDF]
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K. K. Koh, M. J. Quon, S. H. Han, W.-J. Chung, J. Y. Ahn, Y.-H. Seo, M. H. Kang, T. H. Ahn, I. S. Choi, and E. K. Shin Additive Beneficial Effects of Losartan Combined With Simvastatin in the Treatment of Hypercholesterolemic, Hypertensive Patients Circulation, December 14, 2004; 110(24): 3687 - 3692. [Abstract] [Full Text] [PDF]
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A. H. Berg, Y. Lin, M. P. Lisanti, and P. E. Scherer Adipocyte differentiation induces dynamic changes in NF-{kappa}B expression and activity Am J Physiol Endocrinol Metab, December 1, 2004; 287(6): E1178 - E1188. [Abstract] [Full Text] [PDF]
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G. K. Shetty, P. A. Economides, E. S. Horton, C. S. Mantzoros, and A. Veves Circulating Adiponectin and Resistin Levels in Relation to Metabolic Factors, Inflammatory Markers, and Vascular Reactivity in Diabetic Patients and Subjects at Risk for Diabetes Diabetes Care, October 1, 2004; 27(10): 2450 - 2457. [Abstract] [Full Text] [PDF]
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M. Furuhashi, N. Ura, N. Moniwa, Y. Shinshi, H. Kouzu, M. Nishihara, N. Kokubu, T. Takahashi, K.-i. Sakamoto, M. Hayashi, et al. Possible Impairment of Transcardiac Utilization of Adiponectin in Patients With Type 2 Diabetes Diabetes Care, September 1, 2004; 27(9): 2217 - 2221. [Abstract] [Full Text] [PDF]
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H. Staiger, S. Kaltenbach, K. Staiger, N. Stefan, A. Fritsche, A. Guirguis, C. Peterfi, M. Weisser, F. Machicao, M. Stumvoll, et al. Expression of Adiponectin Receptor mRNA in Human Skeletal Muscle Cells Is Related to In Vivo Parameters of Glucose and Lipid Metabolism Diabetes, September 1, 2004; 53(9): 2195 - 2201. [Abstract] [Full Text] [PDF]
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U. Meier and A. M. Gressner Endocrine Regulation of Energy Metabolism: Review of Pathobiochemical and Clinical Chemical Aspects of Leptin, Ghrelin, Adiponectin, and Resistin Clin. Chem., September 1, 2004; 50(9): 1511 - 1525. [Abstract] [Full Text] [PDF]
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S. Bacci, C. Menzaghi, T. Ercolino, X. Ma, A. Rauseo, L. Salvemini, C. Vigna, R. Fanelli, U. Di Mario, A. Doria, et al. The +276 G/T Single Nucleotide Polymorphism of the Adiponectin Gene Is Associated With Coronary Artery Disease in Type 2 Diabetic Patients Diabetes Care, August 1, 2004; 27(8): 2015 - 2020. [Abstract] [Full Text] [PDF]
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