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Department of Cell Biology (M.W.R., P.E.S.) and Diabetes Research and Training Center (P.E.S.), Albert Einstein College of Medicine, Bronx, New York 10461
Address all correspondence and requests for reprints to: Philipp E. Scherer, Diabetes Research and Training Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461. E-mail: scherer{at}aecom.yu.edu.
Adipose tissue evolved to efficiently store energy for times of caloric restriction. The large caloric excess common in many Western diets has negated the need for this thrifty function, leaving adipose tissue ill-equipped to handle this increased load. An excess of adipose tissue increases risk for a number of conditions including coronary artery disease, hypertension, dyslipidemias, type 2 diabetes, and even cancer. Indeed, the ability of the adipocyte to function properly when engorged with lipid can lead to lipid accumulation in other tissues, reducing their ability to function and respond normally. The role of adipose tissue as an endocrine organ capable of secreting a number of adipose tissue-specific or enriched hormones, known as adipokines, is gaining appreciation. The normal balance of these adipose tissue secretory proteins is perturbed in obesity. Paradoxically, the lack of normal adipose tissue, as seen in cases of lipodystrophy and lipoatrophy, is also associated with pathologic sequelae similar to what is seen with obesity. The pathologic findings associated with lack of adipose tissue, largely due to inability to properly store lipids, may also be due to a lack of adipokines. In this review, we highlight the role of adipose tissue as an endocrine organ focusing on some of the recent advances in the identification and pharmacological characterization of adipokines as well as their regulation in the context of obesity and insulin-resistant states.
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D. Dietze-Schroeder, H. Sell, M. Uhlig, M. Koenen, and J. Eckel Autocrine Action of Adiponectin on Human Fat Cells Prevents the Release of Insulin Resistance-Inducing Factors Diabetes, July 1, 2005; 54(7): 2003 - 2011. [Abstract] [Full Text] [PDF]
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M. Bullo, M. R. Peeraully, and P. Trayhurn Stimulation of NGF expression and secretion in 3T3-L1 adipocytes by prostaglandins PGD2, PGJ2, and {Delta}12-PGJ2 Am J Physiol Endocrinol Metab, July 1, 2005; 289(1): E62 - E67. [Abstract] [Full Text] [PDF]
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T. P. Combs, Nagajyothi, S. Mukherjee, C. J. G. de Almeida, L. A. Jelicks, W. Schubert, Y. Lin, D. S. Jayabalan, D. Zhao, V. L. Braunstein, et al. The Adipocyte as an Important Target Cell for Trypanosoma cruzi Infection J. Biol. Chem., June 24, 2005; 280(25): 24085 - 24094. [Abstract] [Full Text] [PDF]
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J. Park, H. K. Rho, K. H. Kim, S. S. Choe, Y. S. Lee, and J. B. Kim Overexpression of Glucose-6-Phosphate Dehydrogenase Is Associated with Lipid Dysregulation and Insulin Resistance in Obesity Mol. Cell. Biol., June 15, 2005; 25(12): 5146 - 5157. [Abstract] [Full Text] [PDF]
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 A Schaffler and H Herfarth Creeping fat in Crohn's disease: travelling in a creeper lane of research? Gut, June 1, 2005; 54(6): 742 - 744. [Full Text] [PDF]
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E. Bugianesi, U. Pagotto, R. Manini, E. Vanni, A. Gastaldelli, R. de Iasio, E. Gentilcore, S. Natale, M. Cassader, M. Rizzetto, et al. Plasma Adiponectin in Nonalcoholic Fatty Liver Is Related to Hepatic Insulin Resistance and Hepatic Fat Content, Not to Liver Disease Severity J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3498 - 3504. [Abstract] [Full Text] [PDF]
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P. Linscheid, D. Seboek, H. Zulewski, U. Keller, and B. Muller Autocrine/Paracrine Role of Inflammation-Mediated Calcitonin Gene-Related Peptide and Adrenomedullin Expression in Human Adipose Tissue Endocrinology, June 1, 2005; 146(6): 2699 - 2708. [Abstract] [Full Text] [PDF]
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 F. Capozza, T. P. Combs, A. W. Cohen, Y.-R. Cho, S.-Y. Park, W. Schubert, T. M. Williams, D. L. Brasaemle, L. A. Jelicks, P. E. Scherer, et al. Caveolin-3 knockout mice show increased adiposity and whole body insulin resistance, with ligand-induced insulin receptor instability in skeletal muscle Am J Physiol Cell Physiol, June 1, 2005; 288(6): C1317 - C1331. [Abstract] [Full Text] [PDF]
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E. Velkoska, T. J. Cole, and M. J. Morris Early dietary intervention: long-term effects on blood pressure, brain neuropeptide Y, and adiposity markers Am J Physiol Endocrinol Metab, June 1, 2005; 288(6): E1236 - E1243. [Abstract] [Full Text] [PDF]
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A. H. Berg and P. E. Scherer Adipose Tissue, Inflammation, and Cardiovascular Disease Circ. Res., May 13, 2005; 96(9): 939 - 949. [Abstract] [Full Text] [PDF]
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J. P. McGillis White Adipose Tissue, Inert No More! Endocrinology, May 1, 2005; 146(5): 2154 - 2156. [Full Text] [PDF]
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J. A. Sennello, R. Fayad, A. M. Morris, R. H. Eckel, E. Asilmaz, J. Montez, J. M. Friedman, C. A. Dinarello, and G. Fantuzzi Regulation of T Cell-Mediated Hepatic Inflammation by Adiponectin and Leptin Endocrinology, May 1, 2005; 146(5): 2157 - 2164. [Abstract] [Full Text] [PDF]
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K. Sjoholm, J. Palming, L. E. Olofsson, A. Gummesson, P.-A. Svensson, T. C. Lystig, E. Jennische, J. Brandberg, J. S. Torgerson, B. Carlsson, et al. A Microarray Search for Genes Predominantly Expressed in Human Omental Adipocytes: Adipose Tissue as a Major Production Site of Serum Amyloid A J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2233 - 2239. [Abstract] [Full Text] [PDF]
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B. Wang, J. R. Jenkins, and P. Trayhurn Expression and secretion of inflammation-related adipokines by human adipocytes differentiated in culture: integrated response to TNF-{alpha} Am J Physiol Endocrinol Metab, April 1, 2005; 288(4): E731 - E740. [Abstract] [Full Text] [PDF]
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P. Trayhurn Adipose Tissue in Obesity--An Inflammatory Issue Endocrinology, March 1, 2005; 146(3): 1003 - 1005. [Full Text] [PDF]
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S. A. Summers and D. H. Nelson A Role for Sphingolipids in Producing the Common Features of Type 2 Diabetes, Metabolic Syndrome X, and Cushing's Syndrome Diabetes, March 1, 2005; 54(3): 591 - 602. [Abstract] [Full Text] [PDF]
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M. Lappas, K. Yee, M. Permezel, and G. E. Rice Sulfasalazine and BAY 11-7082 Interfere with the Nuclear Factor-{kappa}B and I{kappa}B Kinase Pathway to Regulate the Release of Proinflammatory Cytokines from Human Adipose Tissue and Skeletal Muscle in Vitro Endocrinology, March 1, 2005; 146(3): 1491 - 1497. [Abstract] [Full Text] [PDF]
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T. Skurk, C. Herder, I. Kraft, S. Muller-Scholze, H. Hauner, and H. Kolb Production and Release of Macrophage Migration Inhibitory Factor from Human Adipocytes Endocrinology, March 1, 2005; 146(3): 1006 - 1011. [Abstract] [Full Text] [PDF]
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 M. P. Reilly, M. Lehrke, M. L. Wolfe, A. Rohatgi, M. A. Lazar, and D. J. Rader Resistin Is an Inflammatory Marker of Atherosclerosis in Humans Circulation, February 22, 2005; 111(7): 932 - 939. [Abstract] [Full Text] [PDF]
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A M Diehl, Z P Li, H Z Lin, and S Q Yang Cytokines and the pathogenesis of non-alcoholic steatohepatitis Gut, February 1, 2005; 54(2): 303 - 306. [Full Text] [PDF]
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 M. A. Lazar How Obesity Causes Diabetes: Not a Tall Tale Science, January 21, 2005; 307(5708): 373 - 375. [Abstract] [Full Text] [PDF]
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 S. T. Page, K. L. Herbst, J. K. Amory, A. D. Coviello, B. D. Anawalt, A. M. Matsumoto, and W. J. Bremner Testosterone Administration Suppresses Adiponectin Levels in Men J Androl, January 1, 2005; 26(1): 85 - 92. [Abstract] [Full Text] [PDF]
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W. Verreth, D. De Keyzer, M. Pelat, P. Verhamme, J. Ganame, J. K. Bielicki, A. Mertens, R. Quarck, N. Benhabiles, G. Marguerie, et al. Weight Loss-Associated Induction of Peroxisome Proliferator-Activated Receptor-{alpha} and Peroxisome Proliferator-Activated Receptor-{gamma} Correlate With Reduced Atherosclerosis and Improved Cardiovascular Function in Obese Insulin-Resistant Mice Circulation, November 16, 2004; 110(20): 3259 - 3269. [Abstract] [Full Text] [PDF]
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J. J. Rochford, R. K. Semple, M. Laudes, K. B. Boyle, C. Christodoulides, C. Mulligan, C. J. Lelliott, S. Schinner, D. Hadaschik, M. Mahadevan, et al. ETO/MTG8 Is an Inhibitor of C/EBP{beta} Activity and a Regulator of Early Adipogenesis Mol. Cell. Biol., November 15, 2004; 24(22): 9863 - 9872. [Abstract] [Full Text] [PDF]
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J. Klein, S. Westphal, D. Kraus, B. Meier, N. Perwitz, V. Ott, M. Fasshauer, and H H. Klein Metformin inhibits leptin secretion via a mitogen-activated protein kinase signalling pathway in brown adipocytes J. Endocrinol., November 1, 2004; 183(2): 299 - 307. [Abstract] [Full Text] [PDF]
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S.-k. Park, S.-Y. Oh, M.-Y. Lee, S. Yoon, K.-S. Kim, and J.-w. Kim CCAAT/Enhancer Binding Protein and Nuclear Factor-Y Regulate Adiponectin Gene Expression in Adipose Tissue Diabetes, November 1, 2004; 53(11): 2757 - 2766. [Abstract] [Full Text] [PDF]
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 J. R. Schelling and J. R. Sedor The Metabolic Syndrome as a Risk Factor for Chronic Kidney Disease: More than a Fat Chance? J. Am. Soc. Nephrol., November 1, 2004; 15(11): 2773 - 2774. [Full Text] [PDF]
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B. E. Wisse The Inflammatory Syndrome: The Role of Adipose Tissue Cytokines in Metabolic Disorders Linked to Obesity J. Am. Soc. Nephrol., November 1, 2004; 15(11): 2792 - 2800. [Abstract] [Full Text] [PDF]
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K. E. Davis, M. Moldes, and S. R. Farmer The Forkhead Transcription Factor FoxC2 Inhibits White Adipocyte Differentiation J. Biol. Chem., October 8, 2004; 279(41): 42453 - 42461. [Abstract] [Full Text] [PDF]
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