Hostname: page-component-cd9895bd7-gvvz8 Total loading time: 0 Render date: 2024-12-22T15:36:31.817Z Has data issue: false hasContentIssue false
  • English
  • Français

Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ

Published online by Cambridge University Press:  05 March 2007

Paul Trayhurn  and
John H. Beattie
Paul Trayhurn*
Affiliation:
Institute for Nutrition Research, University of Oslo, PO Box 1046 Blindern, N-0316 Oslo, Norway
John H. Beattie
Affiliation:
Rowett Research Institute, Bucksburn, Aberdeen AB21 9SB, UK
*
*Corresponding Author: Professor Paul Trayhurn, present address Department of Medicine, University of Liverpool, University Clinical Departments, Liverpool L69 3GA, UK, fax +44 151 706 5802, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

The traditional role attributed to white adipose tissue is energy storage, fatty acids being released when fuel is required. The metabolic role of white fat is, however, complex. For example, the tissue is needed for normal glucose homeostasis and a role in inflammatory processes has been proposed. A radical change in perspective followed the discovery of leptin; this critical hormone in energy balance is produced principally by white fat, giving the tissue an endocrine function. Leptin is one of a number of proteins secreted from white adipocytes, which include angiotensinogen, adipsin, acylation-stimulating protein, adiponectin, retinol-binding protein, tumour neorosis factor a, interleukin 6, plasminogen activator inhibitor-1 and tissue factor. Some of these proteins are inflammatory cytokines, some play a role in lipid metabolism, while others are involved in vascular haemostasis or the complement system. The effects of specific proteins may be autocrine or paracrine, or the site of action may be distant from adipose tissue. The most recently described adipocyte secretory proteins are fasting-induced adipose factor, a fibrinogen–angiopoietin-related protein, metallothionein and resistin. Resistin is an adipose tissue-specific factor which is reported to induce insulin resistance, linking diabetes to obesity. Metallothionein is a metal-binding and stress-response protein which may have an antioxidant role. The key challenges in establishing the secretory functions of white fat are to identify the complement of secreted proteins, to establish the role of each secreted protein, and to assess the pathophysiological consequences of changes in adipocyte protein production with alterations in adiposity (obesity, fasting, cachexia). There is already considerable evidence of links between increased production of some adipocyte factors and the metabolic and cardiovascular complications of obesity. In essence, white adipose tissue is a major secretory and endocrine organ involved in a range of functions beyond simple fat storage.

Keywords

CytokinesFasting-induced adipose factorLeptinMetallothioneinResistin
Type
Symposium on ‘New perspectives on adipose tissue function’
Information
Proceedings of the Nutrition Society , Volume 60 , Issue 3 , August 2001 , pp. 329 - 339
Copyright
Copyright © The Nutrition Society 2001

References

Ahima, RS & Flier, JS (2000) Adipose tissue as an endocrine organ. Trends in Endocrinology and Metabolism 11, 327–332.CrossRefGoogle ScholarPubMed
Ahima, RS, Prabakaran, D, Mantzoros, C, Qu, DQ, Lowell, B, Maratos-Flier, E & Flier, JS (1996) Role of leptin in the neuroendocrine response to fasting. Nature 382, 250–252.CrossRefGoogle ScholarPubMed
Ahima, RS, Saper, CB, Flier, JS & Elmquist, JK (2000) Leptin regulation of neuroendocrine systems. Frontiers in Neuroendocrinology 21, 263–307.CrossRefGoogle ScholarPubMed
Ailhaud, G (2000) Adipose tissue as an endocrine organ. International Journal of Obesity 24, Suppl. 2, S1–S3.CrossRefGoogle ScholarPubMed
Ailhaud, G, Fukamizu, A, Massiera, F, Négrel, R, Saint-Marc, P & Teboul, M (2000) Angiotensinogen, angiotensin II and adipose tissue development. International Journal of Obesity 24, Suppl. 4, S33–S35.CrossRefGoogle ScholarPubMed
Alessi, MC, Bastelica, D, Morange, P, Berthet, B, Leduc, I, Verdier, M, Geel, O & Juhan-Vague, I (2000) Plasminogen activator inhibitor 1, transforming growth factor-beta(1), and BMI are closely associated in human adipose tissue during morbid obesity. Diabetes 49, 1374–1380.CrossRefGoogle ScholarPubMed
Alessi, MC, Peiretti, F, Morange, P, Henry, M, Nalbone, G & Juhan-Vague, I (1997) Production of plasminogen activator inhibitor-1 by human adipose tissue – Possible link between visceral fat accumulation and vascular disease. Diabetes 46, 860–867.CrossRefGoogle ScholarPubMed
Arita, Y, Kihara, S, Ouchi, N, Takahashi, M, Maeda, K, Miyagawa, J, Hotta, K, Shimomura, I, Nakamura, T, Miyaoka, K, Kuriyama, H, Nishida, M, Yamashita, S, Okubo, K, Matsubara, K, Muraguchi, M, Ohmoto, Y, Funahashi, T & Matsuzawa, Y (1999) Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochemical and Biophysical Research Communications 257, 79–83.CrossRefGoogle ScholarPubMed
Bartness, TJ & Bamshad, M (1998) Innervation of mammalian white adipose tissue: implications for the regulation of total body fat. American Journal of Physiology 275, R1399–R1411.Google ScholarPubMed
Bastard, JP, Jardel, C, Bruckert, E, Blondy, P, Capeau, J, Laville, M, Vidal, H & Hainque, B (2000) Elevated levels of interleukin 6 are reduced in serum and subcutaneous adipose tissue of obese women after weight loss. Journal of Clinical Endocrinology and Metabolism 85, 3338–3342.Google ScholarPubMed
Beattie, JH, Black, DJ, Wood, AM & Trayhurn, P (1996) Cold-induced expression of the metallothionein-1 gene in brown adipose-tissue of rats. American Journal of Physiology 270, R971–R977.Google ScholarPubMed
Beattie, JH, Wood, AM, Trayhurn, P, Jasani, J, Vincent, A, McCormack, G & West, AK (2000) Metallothionein is expressed in adipocytes of brown fat and is induced by catecholamines and zinc. American Journal of Physiology 278, R1082–R1089.Google ScholarPubMed
Becker, DJ, Ongemba, LN, Brichard, V, Henquin, JC & Brichard, SM (1995) Diet-induced and diabetes-induced changes of ob gene-expression in rat adipose-tissue. FEBS Letters 371, 324–328.Google Scholar
Bing, C, Frankish, HM, Pickavance, L, Wang, Q, Hopkins, DFC, Stock, MJ & Williams, G (1998) Hyperphagia cold-exposed rats is accompanied by decreased plasma leptin but unchanged hypothalamic NPY. American Journal of Physiology 274, R62–R68.Google ScholarPubMed
Birgel, M, Gottschling-Zeller, H, Rohrig, 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, 1682–1687.CrossRefGoogle ScholarPubMed
Blomhoff, R, Green, MH, Berg, T & Norum, KR (1990) Transport and storage of vitamin A. Science 250, 399–404.CrossRefGoogle ScholarPubMed
Bouloumie, A, Drexler, HCA, Lafontan, M & Busse, R (1998) Leptin, the product of Ob gene, promotes angiogenesis. Circulation Research 83, 1059–1066.CrossRefGoogle Scholar
Bremner, I & Beattie, JH (1990) Metallothionein and the trace minerals. Annual Review of Nutrition 10, 63–83.CrossRefGoogle ScholarPubMed
Campfield, LA, Smith, FJ, Guisez, Y, De Vos, R & Burn, P (1995) Recombinant mouse Ob protein – evidence for a peripheral signal linking adiposity and central neural networks. Science 269, 546–549.CrossRefGoogle ScholarPubMed
Cianflone, K, Maslowska, M & Sniderman, AD (1999) Acylation stimulating protein (ASP), an adipocyte autocrine: new directions. Seminars in Cell and Developmental Biology 10, 31–41.CrossRefGoogle ScholarPubMed
Cigolini, M, Tonoli, M, Borgato, L, Frigotto, L, Manzato, F, Zeminian, S, Cardinale, C, Camin, M, Chiaramonte, E, DeSandre, G & Lunardi, C (1999) Expression of plasminogen activator inhibitor-1 in human adipose tissue: a role for TNF-α? Atherosclerosis 143, 81–90.CrossRefGoogle ScholarPubMed
Considine, RV, Sinha, MK, Heiman, ML, Kriauciunas, A, Stephens, TW, Nyce, MR, Ohannesian, JP, Marco, CC, McKee, LJ, Bauer, TL & Caro, JF (1996) Serum immunoreactive leptin concentrations in normal-weight and obese humans. New England Journal of Medicine 334, 292–295.CrossRefGoogle ScholarPubMed
Cook, KS, Groves, DL, Min, HY & Spiegelman, BM (1985) A developmentally regulated mRNA from 3T3 adipocytes encodes a novel serine protease homologue. Proceedings of the National Academy of Sciences USA 82, 6480–6484.CrossRefGoogle ScholarPubMed
Cook, KS, Min, HY, Johnson, D, Chaplinsky, RJ, Flier, JS, Hunt, CR & Spiegelman, BM (1987) Adipsin: a circulating serine protease homolog secreted by adipose tissue and sciatic nerve. Science 237, 402–405.CrossRefGoogle ScholarPubMed
Coppack, SW (2001) Pro-inflammatory cytokines and adipose tissue. Proceedings of the Nutrition Society 60, 349–356.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, 305–312.CrossRefGoogle ScholarPubMed
El Refaey, H, Ebadi, M, Kuszynski, CA, Sweeney, J, Hamada, FM & Hamed, A (1997) Identification of metallothionein receptors in human astrocytes. Neuroscience Letters 231, 131–134.CrossRefGoogle ScholarPubMed
Emilsson, V, Liu, YL, Cawthorne, MA, Morton, NM & Davenport, M (1997) Expression of the functional leptin receptor mRNA in pancreatic islets and direct inhibitory action of leptin on insulin secretion. Diabetes 46, 313–316.CrossRefGoogle ScholarPubMed
Enerback, S & Gimble, JM (1993) Lipoprotein lipase gene expression – physiological regulators at the transcriptional and post-transcriptional level. Biochimica et Biophysica Acta 1169, 107–125.CrossRefGoogle ScholarPubMed
Engeli, S, Gorzelniak, K, Kreutz, R, Runkel, N, Distler, A & Sharma, AM (1999) Co-expression of renin-angiotensin system genes in human adipose tissue. Journal of Hypertension 17, 555–560.CrossRefGoogle ScholarPubMed
Engeli, S, Negrel, R & Sharma, AM (2000) Physiology and pathophysiology of the adipose tissue renin-angiotensin system. Hypertension 35, 1270–1277.CrossRefGoogle ScholarPubMed
Eriksson, P, Reynisdottir, S, Lonnqvist, F, Stemme, V, Hamsten, A & Arner, P (1998) Adipose tissue secretion of plasminogen activator inhibitor-1 in non-obese and obese individuals. Diabetologia 41, 65–71.CrossRefGoogle ScholarPubMed
Evans, BA, Agar, L & Summers, RJ (1999) The role of the sympathetic nervous system in the regulation of leptin synthesis in C57BL/6 mice. FEBS Letters 444, 149–154.CrossRefGoogle ScholarPubMed
Flier, JS, Cook, KS, Usher, P & Spiegelman, BM (1987) Severely impaired adipsin expression in genetic and acquired obesity. Science 237, 405–408.CrossRefGoogle ScholarPubMed
Frayn, KN (1999) Macronutrient metabolism of adipose tissue at rest and during exercise: a methodological viewpoint. Proceedings of the Nutrition Society 58, 877–885.CrossRefGoogle ScholarPubMed
Friedman, JM & Halaas, JL (1998) Leptin and the regulation of body weight in mammals. Nature 395, 763–770.CrossRefGoogle ScholarPubMed
Garofalo, MAR, Kettelhut, IC, Roselino, JES & Migliorini, RH (1996) Effect of acute cold exposure on norepinephrine turnover rates in rat white adipose tissue. Journal of the Autonomic Nervous System 60, 206–208.CrossRefGoogle ScholarPubMed
Gettys, TW, Harkness, PJ & Watson, PM (1996) The b(3)-adrenergic receptor inhibits insulin-stimulated leptin secretion from isolated rat adipocytes. Endocrinology 137, 4054–4057.CrossRefGoogle Scholar
Giacobino, JP (1996) Role of the b(3)-adrenoceptor in the control of leptin expression. Hormone and Metabolic Research 28, 633–637.CrossRefGoogle Scholar
Guan, XM, Hess, JF, Yu, H, Hey, PJ & van der Ploeg, LHT (1997) Differential expression of mRNA for leptin receptor isoforms in the rat brain. Molecular and Cellular Endocrinology 133, 1–7.CrossRefGoogle ScholarPubMed
Håkansson, ML, Brown, H, Ghilardi, N, Skoda, RC & Meister, B (1998) Leptin receptor immunoreactivity in chemically defined target neurons of the hypothalamus. Journal of Neuroscience 18, 559–572.CrossRefGoogle ScholarPubMed
Halaas, JL, Gajiwala, KS, Maffei, M, Cohen, SL, Chait, BT, Rabinowitz, D, Lallone, RL, Burley, SK & Friedman, JM (1995) Weight-reducing effects of the plasma-protein encoded by the obese gene. Science 269, 543–546.CrossRefGoogle ScholarPubMed
Hales, CN, Luzio, JP & Siddle, K (1978) Hormonal control of adipose tissue lipolysis. Biochemical Society Transactions 43, 97–135.Google Scholar
Hardie, LJ, Rayner, DV, Holmes, S & Trayhurn, P (1996) Circulating leptin levels are modulated by fasting, cold exposure and insulin administration in lean but not Zucker (fa/fa) rats as measured by ELISA. Biochemical and Biophysical Research Communications 223, 660–665.CrossRefGoogle Scholar
Harp, JB & DiGirolamo, M (1995) Components of the renin-angiotensin system in adipose-tissue – changes with maturation and adipose mass enlargement. Journals of Gerontology 50, B270–B276.Google ScholarPubMed
Harris, RB (2000) Leptin – much more than a satiety signal. Annual Review of Nutrition 20, 45–75.CrossRefGoogle ScholarPubMed
Hausman, GJ (1985) The comparative anatomy of adipose tissue. In New Perspectives in Adipose Tissue: Structure, Function and Development, pp. 1–21 [Cryer, A and Van, RL, editors]. London: Butterworths.Google Scholar
Haynes, WG, Morgan, DA, Walsh, SA, Mark, AL & Sivitz, WI (1997) Receptor-mediated regional sympathetic nerve activation by leptin. Journal of Clinical Investigation 100, 270–278.CrossRefGoogle ScholarPubMed
Hoggard, N, Mercer, JG, Rayner, DV, Moar, K, Trayhurn, P & Williams, LM (1997) Localization of leptin receptor mRNA splice variants in murine peripheral tissues by RT-PCR and in situ hybridization. Biochemical and Biophysical Research Communications 232, 383–387.CrossRefGoogle ScholarPubMed
Holcomb, IN, Kabakoff, RC, Chan, B, Baker, TW, Gurney, A, Henzel, W, Nelson, C, Lowman, HB, Wright, BD, Skelton, NJ, Frantz, GD, Tumas, DB, Peale, F, Shelton, DL & Hebert, CC (2000) FIZZ1, a novel cysteine-rich secreted protein associated with pulmonary inflammation, defines a new gene family. EMBO Journal 19, 4046–4055.CrossRefGoogle ScholarPubMed
Hotamisligil, GS (2000) Molecular mechanisms of insulin resistance and the role of the adipocyte. International Journal of Obesity 24, S23–S27.CrossRefGoogle ScholarPubMed
Hotamisligil, GS, Shargill, NS & Spiegelman, BM (1993) Adipose expression of tumor necrosis factor-a – direct role in obesity-linked insulin resistance. Science 259, 87–91.CrossRefGoogle Scholar
Hotta, K, Funahashi, T, Arita, Y, Takahashi, M, Matsuda, M, Okamoto, Y, Iwahashi, H, Kuriyama, H, Ouchi, N, Maeda, K, Nishida, M, Kihara, S, Sakai, N, Nakajima, T, Hasegawa, K, Muraguchi, M, Ohmoto, Y, Nakamura, T, Yamashita, S, Hanafusa, T & Matsuzawa, Y (2000) Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arteriosclerosis Thrombosis and Vascular Biology 20, 1595–1599.CrossRefGoogle ScholarPubMed
Hube, F, Lietz, U, Igel, M, Jensen, PB, Tornqvist, H, Joost, HG & Hauner, H (1996) Difference in leptin mRNA levels between omental and subcutaneous abdominal adipose tissue from obese humans. Hormone and Metabolic Research 28, 690–693.CrossRefGoogle ScholarPubMed
Juhan-Vague, I & Alessi, MC (1997) PAI-1, obesity, insulin resistance and risk of cardiovascular events. Thrombosis and Haemostasis 78, 656–660.Google ScholarPubMed
Karlsson, C, Lindell, K, Ottosson, M, Sjostrom, L, Carlsson, B & Carlsson, LMS (1998) Human adipose tissue expresses angiotensinogen and enzymes required for its conversion to angiotensin II. Journal of Clinical Endocrinology and Metabolism 83, 3925–3929.Google ScholarPubMed
Kersten, S, Mandard, S, Tan, NS, Escher, P, Metzger, D, Chambon, P, Gonzalez, FJ, Desvergne, B & Wahli, W (2000) Characterization of the fasting-induced adipose factor FIAF, a novel peroxisome proliferator-activated receptor target gene. Journal of Biological Chemistry 275, 28488–28493.CrossRefGoogle ScholarPubMed
Landsberg, L & Young, JB (1984) The role of the sympathoadrenal system in modulating energy expenditure. Clinics in Endocrinology and Metabolism 13, 475–499.CrossRefGoogle ScholarPubMed
Lee, GH, Proenca, R, Montez, JM, Carroll, KM, Darvishzadeh, JG, Lee, JI & Friedman, JM (1996) Abnormal splicing of the leptin receptor in diabetic mice. Nature 379, 632–635.CrossRefGoogle ScholarPubMed
Lord, GM, Matarese, G, Howard, LK, Baker, RJ, Bloom, SR & Lechler, RI (1998) Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature 394, 897–901.CrossRefGoogle ScholarPubMed
Lostao, MP, Urdaneta, E, Martinez-Anso, E, Barber, A & Martinez, JA (1998) Presence of leptin receptors in rat small intestine and leptin effect on sugar absorption. FEBS Letters 423, 302–306.CrossRefGoogle ScholarPubMed
Lundgren, CH, Brown, SL, Nordt, TK, Sobel, BE & Fujii, S (1996) Elaboration of type-1 plasminogen activator inhibitor from adipocytes – A potential pathogenetic link between obesity and cardiovascular disease. Circulation 93, 106–110.CrossRefGoogle ScholarPubMed
Maeda, K, Okubo, K, Shimomura, I, Mizuno, K, Matsuzawa, Y & Matsubara, K (1997) Analysis of an expression profile of genes in the human adipose tissue. Gene 190, 227–235.CrossRefGoogle ScholarPubMed
Makover, A, Soprano, DR, Wyatt, ML & Goodman, DS (1989) Localization of retinol-binding protein mRNA in the rat kidney and in perinephric fat tissue. Journal of Lipid Research 30, 171–180.CrossRefGoogle ScholarPubMed
Mantzoros, CS, Qu, DQ, Frederich, RC, Susulic, VS, Lowell, BB, Maratos-Flier, E & Flier, JS (1996) Activation of β3 adrenergic receptors suppresses leptin expression and mediates a leptin-independent inhibition of food intake in mice. Diabetes 45, 909–914.CrossRefGoogle ScholarPubMed
Mercer, JG, Hoggard, N, Williams, LM, Lawrence, CB, Hannah, LT & Trayhurn, P (1996) Localization of leptin receptor mRNA and the long form splice variant (Ob-Rb) in mouse hypothalamus and adjacent brain regions by in situ hybridization. FEBS Letters 387, 113–116.CrossRefGoogle Scholar
Migliorini, RH, Garofalo, MAR & Kettelhut, IC (1997) Increased sympathetic activity in rat white adipose tissue during prolonged fasting. American Journal of Physiology 272, R656–R661.Google ScholarPubMed
Miles, AT, Hawksworth, GM, Beattie, JH & Rodilla, V (2000) Induction, regulation, degradation and biological significance of mammalian metallothioneins. Critical Reviews in Biochemistry and Molecular Biology 35, 35–70.CrossRefGoogle ScholarPubMed
Mohamed-Ali, V, Goodrick, S, Bulmer, K, Holly, JMP, Yudkin, JS & Coppack, SW (1999) Production of soluble tumor necrosis factor receptors by human subcutaneous adipose tissue in vivo. American Journal of Physiology 277, E971–E975.Google ScholarPubMed
Mohamed-Ali, V, Pinkney, JH & Coppack, SW (1998) Adipose tissue as an endocrine and paracrine organ. International Journal of Obesity 22, 1145–1158.CrossRefGoogle ScholarPubMed
Moitra, J, Mason, MM, Olive, M, Krylov, D, Gavrilova, O, Marcus-Samuels, B, Feigenbaum, L, Lee, E, Aoyama, T, Eckhaus, M, Reitman, ML & Vinson, C (1998) Life without white fat: a transgenic mouse. Genes and Development 12, 3168–3181.CrossRefGoogle ScholarPubMed
Montague, CT, Prins, JB, Sanders, L, Digby, JE & O'Rahilly, S (1997) Depot- and sex-specific differences in human leptin mRNA expression: Implications for the control of regional fat distribution. Diabetes 46, 342–347.CrossRefGoogle ScholarPubMed
Montague, CT, Prins, JB, Sanders, L, Zhang, JL, Sewter, CP, Digby, J, Byrne, CD & O'Rahilly, S (1998) Depot-related gene expression in human subcutaneous and omental adipocytes. Diabetes 47, 1384–1391.CrossRefGoogle ScholarPubMed
Murray, I, Sniderman, AD & Cianflone, K (1999a) Mice lacking acylation stimulating protein (ASP) have delayed postprandial triglyceride clearance. Journal of Lipid Research 40, 1671–1676.CrossRefGoogle ScholarPubMed
Murray, I, Sniderman, AD, Havel, PJ & Cianflone, K (1999b) Acylation stimulating protein (ASP) deficiency alters postprandial and adipose tissue metabolism in male mice. Journal of Biological Chemistry 274, 36219–36225.CrossRefGoogle ScholarPubMed
Mutch, NJ, Wilson, HM, Booth, NA (2001) Plasminogen activator inhibitor-1 and haemostasis in obesity. Proceedings of the Nutrition Society 60, 341–341.CrossRefGoogle ScholarPubMed
Nakata, M, Yada, T, Soejima, N & Maruyama, I (1999) Leptin promotes aggregation of human platelets via the long form of its receptor. Diabetes 48, 426–429.CrossRefGoogle Scholar
Niijima, A (1998) Afferent signals from leptin sensors in the white adipose tissue of the epididymis, and their reflex effect in the rat. Journal of the Autonomic Nervous System 73, 19–25.CrossRefGoogle ScholarPubMed
Ostlund, RE, Yang, JW, Klein, S & Gingerich, R (1996) Relation between plasma leptin concentration and body fat, gender, diet, age, and metabolic covariates. Journal of Clinical Endocrinology and Metabolism 81, 3903–3913.Google ScholarPubMed
Ouchi, N, Kihara, S, Arita, Y, Maeda, K, Kuriyama, H, Okamoto, Y, Hotta, K, Nishida, M, Takahashi, M, Nakamura, T, Yamashita, S, Funahashi, T & Matsuzawa, Y (1999) Novel modulator for endothelial adhesion molecules – Adipocyte-derived plasma protein adiponectin. Circulation 100, 2473–2476.CrossRefGoogle ScholarPubMed
Pelleymounter, MA, Cullen, MJ, Baker, MB, Hecht, R, Winters, D, Boone, T & Collins, F (1995) Effects of the obese gene-product on body-weight regulation in ob/ob mice. Science 269, 540–543.CrossRefGoogle ScholarPubMed
Radeau, T, Robb, M, Lau, P, Borthwick, J & McPherson, R (1998a) Relationship of adipose tissue cholesteryl ester transfer protein (CETP) mRNA to plasma concentrations of CETP in man. Atherosclerosis 139, 369–376.CrossRefGoogle ScholarPubMed
Radeau, T, Robb, M, McDonnell, M & McPherson, R (1998b) Preferential expression of cholesteryl ester transfer protein mRNA by stromal-vascular cells of human adipose tissue. Biochimica et Biophysica Acta 1392, 245–253.CrossRefGoogle ScholarPubMed
Rayner, DV, Dalgliesh, GD, Duncan, JS, Hardie, LJ, Hoggard, N & Trayhurn, P (1997) Postnatal development of the ob gene system: Elevated leptin levels in suckling fa/fa rats. American Journal of Physiology 273, R446–R450.Google ScholarPubMed
Rayner, DV, Simon, E, Duncan, JS & Trayhurn, P (1998) Hyperleptinaemia in mice induced by administration of the tyrosine hydroxylase inhibitor a-methyl-p-tyrosine. FEBS Letters 429, 395–398.CrossRefGoogle Scholar
Safonova, I, Aubert, J, Négrel, R & Ailhaud, G (1997) Regulation by fatty acids of angiotensinogen gene expression in preadipose cells. Biochemical Journal 322, 235–239.CrossRefGoogle ScholarPubMed
Sakamoto, T, Woodcock-Mitchell, J, Marutsuka, K, Mitchell, JJ, Sobel, BE & Fujii, S (1999) TNF-α and insulin, alone and synergistically, induce plasminogen activator inhibitor-1 expression in adipocytes. American Journal of Physiology 276, C1391–C1397.CrossRefGoogle ScholarPubMed
Samad, F & Loskutoff, DJ (1997) The fat mouse: A powerful genetic model to study elevated plasminogen activator inhibitor 1 in Obesity/NIDDM. Thrombosis and Haemostasis 78, 652–655.Google Scholar
Samad, F, Pandey, M & Loskutoff, DJ (1998) Tissue factor gene expression in the adipose tissues of obese mice. Proceedings of the National Academy of Sciences USA 95, 7591–7596.CrossRefGoogle ScholarPubMed
Samad, F, Uysal, KT, Wiesbrock, SM, Pandey, M, Hotamisligil, GS & Loskutoff, DJ (1999) Tumor necrosis factor a is a key component in the obesity-linked elevation of plasminogen activator inhibitor 1. Proceedings of the National Academy of Sciences USA 96, 6902–6907.CrossRefGoogle ScholarPubMed
Samad, F, Yamamoto, K & Loskutoff, DJ (1996) Distribution and regulation of plasminogen activator inhibitor-1 in murine adipose tissue in vivo – Induction by tumor necrosis factor-a and lipopolysaccharide. Journal of Clinical Investigation 97, 37–46.CrossRefGoogle Scholar
Samad, F, Yamamoto, K, Pandey, M & Loskutoff, DJ (1997) Elevated expression of transforming growth factor-b in adipose tissue from obese mice. Molecular Medicine 3, 37–48.CrossRefGoogle Scholar
Sethi, JK & Hotamisligil, GS (1999) The role of TNFa in adipocyte metabolism. Seminars in Cell and Developmental Biology 10, 19–29.CrossRefGoogle ScholarPubMed
Shimomura, I, Hammer, RE, Richardson, JA, Ikemoto, S, Bashmakov, Y, Goldstein, JL & Brown, MS (1998) Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue: model for congenital generalized lipodystrophy. Genes and Development 12, 3182–3194.CrossRefGoogle ScholarPubMed
Sierra-Honigmann, MR, Nath, AK, Murakami, C, Garcia-Cardena, G, Papapetropoulos, A, Sessa, WC, Madge, LA, Schechner, JS, Schwabb, MB, Polverini, PJ & Flores-Riveros, JR (1998) Biological action of leptin as an angiogenic factor. Science 281, 1683–1686.CrossRefGoogle ScholarPubMed
Sivitz, WI, Fink, BD, Morgan, DA, Fox, JM, Donohoue, PA & Haynes, WG (1999) Sympathetic inhibition, leptin, and uncoupling protein subtype expression in normal fasting rats. American Journal of Physiology 277, E668–E677.Google ScholarPubMed
Stehling, O, Döring, H, Nusslein-Hildesheim, B, Olbort, M & Schmidt, I (1997) Leptin does not reduce body fat content but augments cold defense abilities in thermoneutrally reared rat pups. Pfl¨gers Archiv – European Journal of Physiology 434, 694–697.CrossRefGoogle Scholar
Stephens, TW, Basinski, M, Bristow, PK, Buevalleskey, JM, Burgett, SG, Craft, L, Hale, J, Hoffmann, J, Hsiung, HM, Kriauciunas, A, Mackellar, W, Rosteck, PR, Schoner, B, Smith, D, Tinsley, FC, Zhang, XY & Heiman, M (1995) The role of neuropeptide-Y in the antiobesity action of the obese gene-product. Nature 377, 530–532.CrossRefGoogle ScholarPubMed
Steppan, CM, Bailey, ST, Bhat, S, Brown, EJ, Banerjee, RR, Wright, CM, Patel, HR, Ahima, RS & Lazar, MA (2001a) The hormone resistin links obesity to diabetes. Nature 409, 307–312.CrossRefGoogle ScholarPubMed
Steppan, CM, Brown, EJ, Wright, CM, Bhat, S, Banerjee, RR, Dai, CY, Enders, GH, Silberg, DG, Wen, X, Wu, GD & Lazar, MA (2001b) A family of tissue-specific resistin-like molecules. Proceedings of the National Academy of Sciences USA 98, 502–506.CrossRefGoogle ScholarPubMed
Trayhurn, P, Duncan, JS, Hoggard, N & Rayner, DV (1998) Regulation of leptin production: a dominant role for the sympathetic nervous system? Proceedings of the Nutrition Society 57, 413–419.CrossRefGoogle ScholarPubMed
Trayhurn, P, Duncan, JS & Rayner, DV (1995a) Acute cold-induced suppression of ob (obese) gene-expression in white adipose-tissue of mice – mediation by the sympathetic system. Biochemical Journal 311, 729–733.CrossRefGoogle Scholar
Trayhurn, P, Duncan, JS, Rayner, DV & Hardie, LJ (1996) Rapid inhibition of ob gene expression and circulating leptin levels in lean mice by the β3-adrenoceptor agonists BRL 35135A and ZD2079. Biochemical and Biophysical Research Communications 228, 605–610.CrossRefGoogle Scholar
Trayhurn, P, Duncan, JS, Wood, AM & Beattie, JH (2000a) Metallothionein gene expression and secretion by white adipose tissue. American Journal of Physiology 279, R2329–R2335.Google ScholarPubMed
Trayhurn, P, Duncan, JS, Wood, AM & Beattie, JH (2000b) Regulation of metallothionein gene expression and secretion in rat adipocytes differentiated from preadipocytes in primary culture. Hormone and Metabolic Research 32, 542–547.CrossRefGoogle ScholarPubMed
Trayhurn, P, Hoggard, N, Mercer, JG & Rayner, DV (1999) Leptin: fundamental aspects. International Journal of Obesity 23, 22–28.CrossRefGoogle ScholarPubMed
Trayhurn, P, Hoggard, N & Rayner, DV (2001) White adipose tissue as a secretory and endocrine organ: Leptin and other secreted proteins. In Adipose Tissue [Klaus, S, editor]. Austin, TX: Landes Bioscience (In the Press).Google ScholarPubMed
Trayhurn, P, Thomas, MEA, Duncan, JS & Rayner, DV (1995b) Effects of fasting and refeeding on ob gene-expression in white adipose-tissue of lean and obese (ob/ob) mice. FEBS Letters 368, 488–490.Google Scholar
Tsutsumi, C, Okuno, M, Tannous, L, Piantedosi, R, Allan, M, Goodman, DS & Blaner, WS (1992) Retinoids and retinoid-binding protein expression in rat adipocytes. Journal of Biological Chemistry 267, 1805–1810.CrossRefGoogle ScholarPubMed
Unger, RH, Zhou, YT & Orci, L (1999) Regulation of fatty acid homeostasis in cells: Novel role of leptin. Proceedings of the National Academy of Sciences USA 96, 2327–2332.CrossRefGoogle ScholarPubMed
Yokota, T, Oritani, K, Takahashi, I, Ishikawa, J, Matsuyama, A, Ouchi, N, Kihara, S, Funahashi, T, Tenner, AJ, Tomiyama, Y & Matsuzawa, Y (2000) Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood 96, 1723–1732.CrossRefGoogle ScholarPubMed
Youngström, TG & Bartness, TJ (1998) White adipose tissue sympathetic nervous system denervation increases fat pad mass and fat cell number. American Journal of Physiology 275, R1488–R1493.Google ScholarPubMed
Zhang, HH, Kumar, S, Barnett, AH & Eggo, MC (2000) Ceiling culture of mature human adipocytes: use in studies of adipocyte functions. Journal of Endocrinology 164, 119–128.CrossRefGoogle ScholarPubMed
Zhang, YY, Proenca, R, Maffei, M, Barone, M, Leopold, L & Friedman, JM (1994) Positional cloning of the mouse obese gene and its human homolog. Nature 372, 425–432.CrossRefGoogle Scholar
Zorad, S, Fickova, M, Zelezna, B, Macho, L & Kral, JG (1995) The role of angiotensin II and its receptors in regulation of adipose tissue metabolism and cellularity. General Physiology and Biophysics 14, 383–391.Google ScholarPubMed
Zovich, DC, Orologa, A, Okuno, M, Kong, LW, Talmage, DA, Piantedosi, R, Goodman, DS & Blaner, WS (1992) Differentiation-dependent expression of retinoid-binding proteins in BFC-1 beta adipocytes. Journal of Biological Chemistry 267, 13884–138890.CrossRefGoogle ScholarPubMed