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Secretory factors from human adipose tissue and their functional role

Published online by Cambridge University Press:  07 March 2007

Hans Hauner*
Affiliation:
Else Kröner-Fresenius-Centre for Nutritional Medicine of the Technical University of Munich,Klinikum Rechts der Isar, Ismaninger Str. 22, 81675 Munich, Germany
*
Corresponding author: Professor Hans Hauner, fax +49 8161 71 2097, email [email protected]
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Abstract

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Obesity is characterized by an expanded adipose tissue mass. Recent data suggest that adipose tissue is a multi-functional organ rather than simply a passive storage site for excess energy. It has been clearly demonstrated that human adipose tissue produces a variety of secretory factors that exert multiple effects at both the local and the systemic level. To date, >100 products, covering a broad range of protein families as well as many fatty acids and prostaglandins, have been reported to be secreted by adipose tissue. The source of these secreted factors is not only mature fat cells but also poorly-identified cells present in the stromal–vascular fraction including macrophages. Secreted factors of particular interest include many cytokines or chemokines, such as TNF-α, IL-6, IL-8, as well as plasminogen activator inhibitor-1, angiotensin-II, leptin, and adiponectin. In the obese state the expression and secretion of these factors is disturbed. With the exception of adiponectin, most circulating factors are elevated. From this perspective, obesity can be described as a pro-inflammatory condition. In addition, regional differences in adipose expression of many of these factors have been found. There is now growing evidence that many secretory factors play an important role in the pathophysiology of the metabolic and cardiovascular complications of obesity. The question arising from these observations is how the secretory pattern of adipose tissue can be modified by dietary and pharmacological measures to reduce the health risks of obesity.

Type
Symposium on ‘Biology of obesity’
Copyright
Copyright © The Nutrition Society 2005

References

Ailhaud, G & Hauner, H (2004) Development of white adipose tissue. In Handbook of Obesity. Etiology and Pathophysiology 2nd ed., pp. 481514 [ Bray, GA and Bouchard, C, editors ] New York: Marcel Dekker.Google Scholar
Alessi, MC, Pirelli, F, Morange, P, Henry, M, Nalbone, G & Juhan-Vague, I (1997) Production of plasminogen activator inhibitor-1 by adipose tissue: possible link between visceral fat accumulation and vascular disease. Diabetes 46, 860867.CrossRefGoogle ScholarPubMed
Berg, AH, Combs, TP & Scherer, PE (2002) ACRP30/adiponectin: an adipokine regulating glucose and lipid metabolism. Trends in Endocrinology and Metabolism 13, 8489.CrossRefGoogle ScholarPubMed
Berg, AH, Combs, TP, Du, X, Brownlee, M & Scherer, PE (2001) The adipocyte-secreted protein ACRP30 enhances hepatic insulin action. Nature Medicine 7, 947953.CrossRefGoogle ScholarPubMed
Birgel, M, Gottschling-Zeller, H, Röhrig, K & Hauner, H (2000) Role of cytokines in the regulation of plasminogen activator inhibitor-1 expression and secretion in newly differentiated subcutaneous human adipocytes. Arteriosclerosis, Thrombosis and Vascular Biology 20, 16821687.CrossRefGoogle ScholarPubMed
Boden, G (1997) Role of fatty acids in the pathogenesis of insulin resistance and NIDDM. Diabetes 46, 310.CrossRefGoogle ScholarPubMed
Bornstein, SR, Abu-Asab, M, Glasow, A, Päth, G, Hauner, H, Tsokos, M, Chrousos, GP & Scherbaum, WA (2000) Immunohistochemical and ultrastructural localization of leptin and leptin receptor in human white adipose tissue and differentiating human adipose cells in primary culture. Diabetes 49, 532538.CrossRefGoogle ScholarPubMed
Cousin, B, Munoz, O, Andre, M, Fontanilles, AM, Dani, C, Cousin, JL, Laharrague, P, Casteilla, L & Penicaud, L (1999) A role for preadipocytes as macrophage-like cells. FASEB Journal 13, 305312.CrossRefGoogle ScholarPubMed
Darimont, C, Vassaux, G, Ailhaud, G & Negrel, R (1994) Differentiation of preadipose cells: paracrine role of prostacyclin upon stimulation of adipose cells by angiotensin II. Endocrinology 135, 20302035.CrossRefGoogle ScholarPubMed
Dietze, D, Koenen, M, Röhrig, K, Horikoshi, H, Hauner, H & Eckel, J (2002) Impairment of insulin signalling in human skeletal muscle by co-culture with human adipocytes. Diabetes 51, 23692376.CrossRefGoogle ScholarPubMed
Ehrhart-Bornstein, M, Lamounier-Zepter, V, Schraven, A, Langenbach, J, Willenberg, HS, Barthel, A, Hauner, H, McCann, SM, Scherbaum, WA & Bornstein, SR (2003) Human adipocytes secrete mineralocorticoid-releasing factors. Proceedings of the National Academy of Sciences USA 100, 1421114216.CrossRefGoogle ScholarPubMed
Eriksson, P, Reynisdottir, S, Lönnqvist, F, Stemme, V, Hamsten, A & Arner, P (1998) Adipose secretion of plasminogen activator inhibitor-1 in non-obese and obese individuals. Diabetologia 41, 6571.CrossRefGoogle ScholarPubMed
Fain, JN, Madan, AK, Hiler, ML, Cheema, P & Bahouth, SW (2004) Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissue of obese humans. Endocrinology 145, 22732282.CrossRefGoogle ScholarPubMed
Fried, SK, Bunkin, DA & Greenberg, AS (1998) Omental and subcutaneous adipose tissue of obese subjects release interleukin-6: depot differences and regulation by glucocorticoids. Journal of Clinical Endocrinology and Metabolism 83, 847850.Google Scholar
Friedman, JM & Halass, JL (1998) Leptin and the regulation of body weight in mammals. Nature 395, 763770.CrossRefGoogle ScholarPubMed
Gottschling-Zeller, H, Birgel, M, Röhrig, K & Hauner, H (2000) Effect of tumor necrosis factor alpha and transforming growth factor beta 1 on plasminogen activator inhibitor-1 secretion from subcutaneous and omental human fat cells in suspension culture. Metabolism 49, 666671.CrossRefGoogle ScholarPubMed
Hauner, H (2002) Insulin resistance and the metabolic syndrome – a challenge of the new millenium. European Journal of Clinical Nutrition 56 Suppl. 1, S25S29.CrossRefGoogle Scholar
Hotamisligil, GS, Arner, P, Caro, JF, Atkinson, RL & Spiegelman, BM (1995) Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. Journal of Clinical Investigation 95, 24092415.CrossRefGoogle ScholarPubMed
Hotamisligil, GS, Shargill, NS & Spiegelman, BM (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 257, 8791.CrossRefGoogle Scholar
Hube, F, Birgel, N, Lee, Y-M & Hauner, H (1999) Expression pattern of tumour necrosis factor receptors in subcutaneous and omental human adipose tissue: role of obesity and non-insulin-dependent diabetes mellitus. European Journal of Clinical Investigation 29, 672678.CrossRefGoogle ScholarPubMed
Hube, F & Hauner, H (1999) The role of TNF-α in human adipose tissue: prevention of weight gain at the expense of insulin resistance. Hormone and Metabolic Research 31, 626631.CrossRefGoogle ScholarPubMed
Janke, J, Engeli, S, Gorzelniak, K, Luft, FC & Sharma, AM (2002) Mature adipocytes inhibit in vitro differentiation of human preadipocytes via angiotensin type 1 receptors. Diabetes 51, 16991707.CrossRefGoogle ScholarPubMed
Karlsson, C, Lindell, K, Ottosson, M, Sjöström, L, Carlsson, B & Carlsson, LM (1998) Human adipose tissue expresses angiotensinogen and the enzymes required for its conversion to angiotensin II. Journal of Clinical Endocrinology and Metabolism 83, 39253929.Google Scholar
Kern, PA, Saghizadeh, M, Ong, JM, Bosch, RJ, Deem, R & Simsolo, RB (1995) The expression of tumor necrosis factor in human adipose tissue. Journal of Clinical Investigation 95, 21112119.CrossRefGoogle ScholarPubMed
Lakka, HM, Laaksonen, DE, Lakka, TA, Niskanen, LK, Kumpusalo, E, Tuomilehto, J & Salonen, JT (2002) The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. Journal of the American Medical Association 288, 27092716.CrossRefGoogle ScholarPubMed
Ma, L-J, Mao, S-L, Taylor, KL, Kanjanabuch, T, Guan, YF & Zhang, YH et al. . (2004) Prevention of obesity and insulin resistance in mice lacking plasminogen activator inhibitor-1. Diabetes 53, 336346.CrossRefGoogle ScholarPubMed
Massiera, F, Bloch-Faure, M, Ceiler, D, Murakami, K, Fukamizu, A & Gask, JM et al. . (2001) Adipose angiotensinogen is involved in adipose tissue growth and blood pressure regulation. FASEB Journal 15, 27272729.CrossRefGoogle ScholarPubMed
Mohamed-Ali, V, Goodbrick, S, Rawesh, A, Katz, DR, Miles, JM, Yudkin, JS, Klein, S & Coppack, SW (1997) Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-α in vivo. Journal of Clinical Endocrinology and Metabolism 82, 41964200.Google Scholar
Päth, G, Bornstein, SR, Gurniak, M, Chrousos, GP, Scherbaum, WA & Hauner, H (2001) Human breast adipocytes express interleukin-6 (IL-6) and its receptor system: increased IL-6 production by β-adrenergic activation and effects of IL-6 on adipocyte function. Journal of Clinical Endocrinology and Metabolism 86, 22812288.Google ScholarPubMed
Ridker, PM, Rifai, N, Stampfer, MJ & Hennekens, CH (2000) Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation 101, 17671772.CrossRefGoogle ScholarPubMed
Sattar, N, Gaw, A, Scherbakowa, O, Ford, I, O'Reilly, DS, Haffner, SM, Isles, C, MacFarlane, PW, Packard, CJ, Cobbe, SM & Shepherd, J (2003) Metabolic syndrome with and without C-reactive protein as a predictor of coronary heart disease and diabetes in the West of Scotland Coronary Prevention Study. Circulation 108, 414419.CrossRefGoogle ScholarPubMed
Sawdey, MS & Loskutoff, DJ (1991) Regulation of murine type 1 plasminogen activator inhibitor gene expression in vivo: tissue specificity and induction by lipopolysaccharide, tumor necrosis factor-alpha, and transforming growth factor-beta. Journal of Clinical Investigation 88, 13461353.CrossRefGoogle ScholarPubMed
Skurk, T & Hauner, H (2004) Obesity and impaired fibrinolysis: role of adipose production of plasminogen activator inhibitor-1. International Journal of Obesity and Related Metabolic Disorders 28, 13571364.CrossRefGoogle ScholarPubMed
Skurk, T, Herder, C, Kraft, I, Muller-Scholze, S, Hauner, H & & Kolb, H (2005) Production and release of macrophage migration inhibitory factor from human adipocytes. Endocrinology 146, 10061011; Epublication 2 December 2004.Google Scholar
Skurk, T, Lee, Y-M & Hauner, H (2001) Angiotensin II and its metabolites stimulate PAI-1 protein release from human adipocytes in primary culture. Hypertension 37, 13361340.CrossRefGoogle ScholarPubMed
Skurk, T, van Harmelen, V & Hauner, H (2004) Angiotensin II stimulates the release of interleukin-6 and interleukin-8 from cultured human adipocytes by activation of NF-kappaB. Arteriosclerosis, Thrombosis and Vascular Biology 24, 11991203.CrossRefGoogle ScholarPubMed
Spranger, J, Kroke, A, Möhlig, M, Bergmann, MM, Ristow, M, Boeing, H & Pfeiffer, AF (2003a) Adiponectin and protection against type 2 diabetes. Lancet 361, 226228.CrossRefGoogle ScholarPubMed
Spranger, J, Kroke, A, Möhlig, M, Hoffmann, K, Bergmann, MM, Ristow, M, Boeing, H & Pfeiffer, AF (2003b) Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Diabetes 52, 812817.CrossRefGoogle ScholarPubMed
Umemura, S, Nyui, N, Tamura, K, Hibi, K, Yamaguchi, S, Nakamaru, M, Ishigami, T, Yabana, M, Kihara, M, Inoue, S & Ishii, M (1997) Plasma angiotensinogen concentrations in obesity. American Journal of Hypertension 10, 629633.CrossRefGoogle Scholar
van Harmelen, V, Ariapart, P, Hoffstedt, J, Lundkvist, I, Bringman, S & Arner, P (2000b) Increased adipose angiotensinogen gene expression in human adipose tissue. Obesity Research 8, 337341.CrossRefGoogle Scholar
van Harmelen, V, Elizalde, M, Ariapart, P, Bergstedt-Lindqvist, S, Reynisdottir, S, Hoffstedt, J, Lundqvist, I, Bringman, S & Arner, P (2000b) The association of human adipose tissue angiotensinogen gene expression with abdominal fat distribution in obesity. International Journal of Obesity and Related Metabolic Disorders 24, 673678.CrossRefGoogle ScholarPubMed
van Harmelen, V, Skurk, T, Röhrig, K & Hauner, H (2003) HMG-CoA reductase inhibitor cerivastatin inhibits interleukin-6 expression and secretion in human adipocytes. Hormone and Metabolic Research 35, 466470.Google ScholarPubMed
Weisberg, SP, McCann, D, Desai, M, Rosenbaum, M, Leibel, RL & Ferrante, AW (2003) Obesity is associated with macrophage accumulation in adipose tissue. Journal of Clinical Investigation 112, 17961808.CrossRefGoogle ScholarPubMed
Wellen, KE & Hotamisligil, GS (2003) Obesity-induced inflammatory changes in adipose tissue. Journal of Clinical Investigation 112, 17851788.CrossRefGoogle ScholarPubMed
Weyer, C, Funahashi, T, Tanaka, S, Hotta, K, Matsuzawa, Y, Pratley, RE & Tataranni, PA (2001) Hypoadiponectinemia in obesity and type 2 diabetes: association with insulin resistance and hyperinsulinemia. Journal of Clinical Endocrinology and Metabolism 86, 19301935.CrossRefGoogle ScholarPubMed
Woods, A, Brull, DJ, Humphries, SE & Montgomery, HE (2000) Genetics of inflammation and risk of coronary artery disease: the central role of interleukin-6. European Heart Journal 21, 15741583.CrossRefGoogle Scholar
World Health OrganizationWorld Health Organization (2000) Obesity: Preventing and Managing the Global Epidemic. Report on a WHO consultation. WHO Technical Report Series no. 894. Geneva: WHO.Google Scholar
Xu, H, Barnes, GT, Yang, O, Tan, G, Yang, D, Chou, CJ, Sole, J, Nichols, A, Ross, JS, Tartaglia, LA & Chen, H (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. Journal of Clinical Investigation 112, 18211830.CrossRefGoogle Scholar
Yang, WS, Lee, WJ, Funahashi, T, Tanaka, S, Matsuzawa, Y, Chao, CL, Chen, CL, Tai, TY & Chuang, LM (2001) Weight reduction increases plasma levels of an adipose tissue-derived anti-inflammatory protein, adiponectin. Journal of Clinical Endocrinology and Metabolism 86, 38153819.CrossRefGoogle Scholar
Zhang, Y, Proenca, R, Maffei, M, Barone, M, Leopold, L & Friedman, JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425432.CrossRefGoogle ScholarPubMed