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Adipokines: inflammation and the pleiotropic role of white adipose tissue

  • Paul Trayhurn (a1) and I. Stuart Wood (a1)

White adipose tissue is now recognised to be a multifunctional organ; in addition to the central role of lipid storage, it has a major endocrine function secreting several hormones, notably leptin and adiponectin, and a diverse range of other protein factors. These various protein signals have been given the collective name ‘adipocytokines’ or ‘adipokines’. However, since most are neither ‘cytokines’ nor ‘cytokine-like’, it is recommended that the term ‘adipokine’ be universally adopted to describe a protein that is secreted from (and synthesised by) adipocytes. It is suggested that the term is restricted to proteins secreted from adipocytes, excluding signals released only by the other cell types (such as macrophages) in adipose tissue. The adipokinome (which together with lipid moieties released, such as fatty acids and prostaglandins, constitute the secretome of fat cells) includes proteins involved in lipid metabolism, insulin sensitivity, the alternative complement system, vascular haemostasis, blood pressure regulation and angiogenesis, as well as the regulation of energy balance. In addition, there is a growing list of adipokines involved in inflammation (TNFα, IL-1β, IL-6, IL-8, IL-10, transforming growth factor-β, nerve growth factor) and the acute-phase response (plasminogen activator inhibitor-1, haptoglobin, serum amyloid A). Production of these proteins by adipose tissue is increased in obesity, and raised circulating levels of several acute-phase proteins and inflammatory cytokines has led to the view that the obese are characterised by a state of chronic low-grade inflammation, and that this links causally to insulin resistance and the metabolic syndrome. It is, however, unclear as to the extent to which adipose tissue contributes quantitatively to the elevated circulating levels of these factors in obesity and whether there is a generalised or local state of inflammation. The parsimonious view is that the increased production of inflammatory cytokines and acute-phase proteins by adipose tissue in obesity relates primarily to localised events within the expanding fat depots. It is suggested that these events reflect hypoxia in parts of the growing adipose tissue mass in advance of angiogenesis, and involve the key controller of the cellular response to hypoxia, the transcription factor hypoxia inducible factor-1.

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G Ambrosini , AK Nath , MR Sierra-Honigmann & J Flores-Riveros Transcriptional activation of the human leptin gene in response to hypoxia. Involvement of hypoxia-inducible factor 1. J Biol Chem (2002) 277, 3460134609.

Y Arita , S Kihara & N Ouchi Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun (1999) 257, 7983.

JM Bruun , SB Pedersen & B Richelsen Interleukin-8 production in human adipose tissue. Inhibitory effects of anti-diabetic compounds, the thiazolidinedione ciglitazone and the biguanide metformin. Horm Metab Res (2000) 32, 537541.

M Bulló , P Garcia-Lorda , I Megias & J Salas-Salvado Systemic inflammation, adipose tissue tumor necrosis factor, and leptin expression. Obesity Res (2003) 11, 525531.

GN Chaldakov , IS Stankulov , M Fiore , PI Ghenev & L Aloe Nerve growth factor levels and mast cell distribution in human coronary atherosclerosis. Atherosclerosis (2001) 159, 5766.

M Cigolini , M Tonoli & L Borgato Expression of plasminogen activator inhibitor-1 in human adipose tissue: a role for TNF-α?. Atherosclerosis (1999) 143, 8190.

KS Cook , DL Groves , HY Min & BM Spiegelman A developmentally regulated mRNA from 3T3 adipocytes encodes a novel serine protease homologue. Proc Natl Acad Sci USA (1985) 82, 64806484.

KS Cook , HY Min , D Johnson , RJ Chaplinsky , JS Flier , CR Hunt & BM Spiegelman Adipsin: a circulating serine protease homolog secreted by adipose tissue and sciatic nerve. Science (1987) 237, 402405.

UN Das Is obesity an inflammatory condition?. Nutrition (2001) 17, 953966.

D Dietze , M Koenen , K Rohrig , H Horikoshi , H Hauner & J Eckel Impairment of insulin signaling in human skeletal muscle cells by co-culture with human adipocytes. Diabetes (2002) 51, 23692376.

G Engström , B Hedblad , L Stavenow , P Lind , L Janzon & F Lindgärde Inflammation-sensitive plasma proteins are associated with future weight gain. Diabetes (2003) 52, 20972101.

K Esposito , A Pontillo , M Ciotola , C Di Palo , E Grella , G Nicoletti & D Giugliano Weight loss reduces interleukin-18 levels in obese women. J Clin Endocrinol Metab (2002) 87, 38643866.

JN Fain , SW Bahouth & AK Madan Haptoglobin release by human adipose tissue in primary culture. J Lipid Res (2004 a) 45, 536542.

T Funahashi , T Nakamura , I Shimomura , K Maeda , H Kuriyama , M Takahashi , Y Arita , S Kihara & Y Matsuzawa Role of adipocytokines on the pathogenesis of atherosclerosis in visceral obesity. Intern Med (1999) 38, 202206.

W Hasan , R Zhang , M Liu , JD Warn & PG Smith Coordinate expression of NGF and alpha-smooth muscle actin mRNA and protein in cutaneous wound tissue of developing and adult rats. Cell Tissue Res (2000) 300, 97109.

GS Hotamisligil Inflammatory pathways and insulin action. Int J Obesity, (2003) 27, Suppl. 3. S53S55.

K Hotta , T Funahashi & Y Arita Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscl Thromb Vasc Biol (2000) 20, 15951599.

S Kersten , S Mandard , NS Tan , P Escher , D Metzger , P Chambon , FJ Gonzalez , B Desvergne & W Wahli Characterization of the fasting-induced adipose factor FIAF, a novel peroxisome proliferator-activated receptor target gene. J Biol Chem (2000) 275, 2848828493.

I Kratchmarova , DE Kalume & B Blagoev A proteomic approach for identification of secreted proteins during the differentiation of 3T3-L1 preadipocytes to adipocytes. Mol Cell Proteomics (2002) 1, 213222.

R Levi-Montalcini , SD Skaper , R Dal Toso , L Petrelli & A Leon Nerve growth factor: from neurotrophin to neurokine. Trends Neurosci (1996) 19, 514520.

Y Lin , MW Rajala , JP Berger , DE Moller , N Barzilai & PE Scherer Hyperglycemia-induced production of acute phase reactants in adipose tissue. J Biol Chem (2001) 276, 4207742083.

K Lolmede , de Durand , V Saint Front , J Galitzky , M Lafontan & A Bouloumie Effects of hypoxia on the expression of proangiogenic factors in differentiated 3T3-F442A adipocytes. Int J Obesity (2003) 27, 11871195.

CH Lundgren , SL Brown , TK Nordt , BE Sobel & S Fujii Elaboration of type-1 plasminogen activator inhibitor from adipocytes - a potential pathogenetic link between obesity and cardiovascular disease. Circulation (1996) 93, 106110.

V Mohamed-Ali , S Goodrick , A Rawesh , DR Katz , JM Miles , JS Yudkin , S Klein & SW Coppack Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo. J Clin Endocrinol Metab (1997) 82, 41964200.

V Mohamed-Ali , JH Pinkney & SW Coppack Adipose tissue as an endocrine and paracrine organ. Int J Obesity (1998) 22, 11451158.

do Oller , C Nascimento , L Hunter & P Trayhurn Regulation of haptoglobin gene expression in 3T3-L1 adipocytes by cytokines, catecholamines, and PPARγ. Biochem Biophys Res Commun (2004) 313, 702708.

N Pannacciulli , FP Cantatore , A Minenna , M Bellacicco , R Giorgino & G De Pergola C-reactive protein is independently associated with total body fat, central fat, and insulin resistance in adult women. Int J Obesity (2001) 25, 14161420.

DV Rayner & P Trayhurn Regulation of leptin production: sympathetic nervous system interactions. J Mol Med (2001) 79, 820.

MA Rupnick , D Panigrahy , C-Y Zhang , SM Dallabrida , BB Lowell , R Langer & MJ Folkman Adipose tissue mass can be regulated through the vasculature. Proc Natl Acad Sci USA (2002) 99, 1073010735.

T Starnes , HE Broxmeyer , MJ Robertson & R Hromas Cutting edge: IL-17D, a novel member of the IL-17 family, stimulates cytokine production and inhibits hemopoiesis. J Immunol (2002) 169, 642646.

A Tchernof , A Nolan , CK Sites , PA Ades & ET Poehlman Weight loss reduces C-reactive protein levels in obese postmenopausal women. Circulation (2002) 105, 564569.

CM Uhlar & AS Whitehead Serum amyloid A, the major vertebrate acute-phase reactant. Eur J Biochem (1999) 265, 501523.

JE Volanakis Human C-reactive protein: expression, structure, and function. Mol Immunol (2001) 38, 189197.

B Vozarova , C Weyer , K Hanson , PA Tataranni , C Bogardus & RE Pratley Circulating interleukin-6 in relation to adiposity, insulin action, and insulin secretion. Obesity Res (2001) 9, 414417.

K Wallenius , V Wallenius , D Sunter , SL Dickson & JO Jansson Intracerebroventricular interleukin-6 treatment decreases body fat in rats. Biochem Biophys Res Commun (2002) 293, 560565.

SP Weisberg , D McCann , M Desai , M Rosenbaum , RL Leibel & AW Ferrante Jr Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest (2003) 112, 17961808.

RH Wenger Cellular adaptation to hypoxia: O 2 -sensing protein hydroxylases, hypoxia-inducible transcription factors, and O 2 -regulated gene expression. FASEB J (2002) 16, 11511162.

G Wiesner , BA Morash , E Ur & M Wilkinson Food restriction regulates adipose-specific cytokines in pituitary gland but not in hypothalamus. J Endocrinol (2004) 180, R1R6.

YS Yang , HD Song , RY Li , LB Zhou , ZD Zhu , RM Hu , ZG Han & JL Chen The gene expression profiling of human visceral adipose tissue and its secretory functions. Biochem Biophys Res Commun (2003) 300, 839846.

JC Yoon , TW Chickering , ED Rosen , B Dussault , Y Qin , A Soukas , JM Friedman , WE Holmes & BM Spiegelman Peroxisome proliferator-activated receptor gamma target gene encoding a novel angiopoietin-related protein associated with adipose differentiation. Mol Cell Biol (2000) 20, 53435349.

JS Yudkin , M Kumari , SE Humphries & V Mohamed-Ali Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link?. Atherosclerosis (2000) 148, 209214.

JS Yudkin , CD Stehouwer , JJ Emeis & SW Coppack C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue?. Arterioscler Thromb Vasc Biol (1999) 19, 972978.

YY Zhang , R Proenca , M Maffei , M Barone , L Leopold & JM Friedman Positional cloning of the mouse obese gene and its human homolog. Nature (1994) 372, 425432.

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British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
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