Skip to main content
×
Home
    • Aa
    • Aa

Dietary factors and low-grade inflammation in relation to overweight and obesity

  • Philip C. Calder (a1), Namanjeet Ahluwalia (a2), Fred Brouns (a3) (a4), Timo Buetler (a5) (a6), Karine Clement (a7), Karen Cunningham (a8), Katherine Esposito (a9), Lena S. Jönsson (a10), Hubert Kolb (a11), Mirian Lansink (a12), Ascension Marcos (a13), Andrew Margioris (a14), Nathan Matusheski (a15), Herve Nordmann (a16), John O'Brien (a5), Giuseppe Pugliese (a17), Salwa Rizkalla (a7), Casper Schalkwijk (a18), Jaakko Tuomilehto (a19), Julia Wärnberg (a13) (a20), Bernhard Watzl (a21) and Brigitte M. Winklhofer-Roob (a22)...
Abstract

Low-grade inflammation is a characteristic of the obese state, and adipose tissue releases many inflammatory mediators. The source of these mediators within adipose tissue is not clear, but infiltrating macrophages seem to be especially important, although adipocytes themselves play a role. Obese people have higher circulating concentrations of many inflammatory markers than lean people do, and these are believed to play a role in causing insulin resistance and other metabolic disturbances. Blood concentrations of inflammatory markers are lowered following weight loss. In the hours following the consumption of a meal, there is an elevation in the concentrations of inflammatory mediators in the bloodstream, which is exaggerated in obese subjects and in type 2 diabetics. Both high-glucose and high-fat meals may induce postprandial inflammation, and this is exaggerated by a high meal content of advanced glycation end products (AGE) and partly ablated by inclusion of certain antioxidants or antioxidant-containing foods within the meal. Healthy eating patterns are associated with lower circulating concentrations of inflammatory markers. Among the components of a healthy diet, whole grains, vegetables and fruits, and fish are all associated with lower inflammation. AGE are associated with enhanced oxidative stress and inflammation. SFA and trans-MUFA are pro-inflammatory, while PUFA, especially long-chain n-3 PUFA, are anti-inflammatory. Hyperglycaemia induces both postprandial and chronic low-grade inflammation. Vitamin C, vitamin E and carotenoids decrease the circulating concentrations of inflammatory markers. Potential mechanisms are described and research gaps, which limit our understanding of the interaction between diet and postprandial and chronic low-grade inflammation, are identified.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Dietary factors and low-grade inflammation in relation to overweight and obesity
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about sending content to Dropbox.

      Dietary factors and low-grade inflammation in relation to overweight and obesity
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about sending content to Google Drive.

      Dietary factors and low-grade inflammation in relation to overweight and obesity
      Available formats
      ×
Copyright
Corresponding author
Correspondence: ILSI Europe a.i.s.b.l., Avenue E. Mounier 83, Box 6 – 1200 Brussels, Belgium, fax +32 2 762 00 44, email publications@ilsieurope.be
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

1PC Calder , R Albers , JM Antoine , (2009) Inflammatory disease processes and interactions with nutrition. Br J Nutr 101, Suppl. 1, S145.

2H Kolb & T Mandrup-Poulsen (2010) The global diabetes epidemic as a consequence of lifestyle-induced low-grade inflammation. Diabetologia 53, 1020.

3JM Fernandez-Real & JC Pickup (2008) Innate immunity, insulin resistance and type 2 diabetes. Trends Endocrinol Metab 19, 1016.

4C Herder , M Peltonen , W Koenig , (2006) Systemic immune mediators and lifestyle changes in the prevention of type 2 diabetes: results from the Finnish Diabetes Prevention Study. Diabetes 55, 23402346.

5C Herder , T Illig , W Rathmann , (2005) Inflammation and type 2 diabetes: results from KORA Augsburg. Gesundheitswesen 67, Suppl. 1, S115S121.

6S Muller , S Martin , W Koenig , (2002) Impaired glucose tolerance is associated with increased serum concentrations of interleukin 6 and co-regulated acute-phase proteins but not TNF-alpha or its receptors. Diabetologia 45, 805812.

7CS Kim , HS Park , T Kawada , (2006) Circulating levels of MCP-1 and IL-8 are elevated in human obese subjects and associated with obesity-related parameters. Int J Obes (Lond) 30, 13471355.

8GS Hotamisligil , NS Shargill & BM Spiegelman (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259, 8791.

9P Trayhurn & IS Wood (2004) Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br J Nutr 92, 347355.

10H Tilg & AR Moschen (2006) Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 6, 772783.

11KE Wellen & GS Hotamisligil (2003) Obesity-induced inflammatory changes in adipose tissue. J Clin Invest 112, 17851788.

12A Koerner , J Kratzsch & W Kiess (2005) Adipocytokines: leptin–the classical, resistin–the controversical, adiponectin–the promising, and more to come. Best Pract Res Clin Endocrinol Metab 19, 525546.

13ME Trujillo & PE Scherer (2006) Adipose tissue-derived factors: impact on health and disease. Endocr Rev 27, 762778.

15M Gil-Campos , RR Canete & A Gil (2004) Adiponectin, the missing link in insulin resistance and obesity. Clin Nutr 23, 963974.

16A Fukuhara , M Matsuda , M Nishizawa , (2005) Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science 307, 426430.

17PG McTernan , CM Kusminski & S Kumar (2006) Resistin. Curr Opin Lipidol 17, 170175.

18RZ Yang , MJ Lee , H Hu , (2006) Identification of omentin as a novel depot-specific adipokine in human adipose tissue: possible role in modulating insulin action. Am J Physiol Endocrinol Metab 290, E1253E1261.

19RZ Yang , MJ Lee , H Hu , (2006) Acute-phase serum amyloid A: an inflammatory adipokine and potential link between obesity and its metabolic complications. PLoS Med 3, e287.

20JK Sethi & A Vidal-Puig (2005) Visfatin: the missing link between intra-abdominal obesity and diabetes? Trends Mol Med 11, 344347.

21JM Stephens & AJ Vidal-Puig (2006) An update on visfatin/pre-B cell colony-enhancing factor, an ubiquitously expressed, illusive cytokine that is regulated in obesity. Curr Opin Lipidol 17, 128131.

22I Juhan-Vague , MC Alessi , A Mavri , (2003) Plasminogen activator inhibitor-1, inflammation, obesity, insulin resistance and vascular risk. J Thromb Haemost 1, 15751579.

23C Poitou , N Viguerie , R Cancello , (2005) Serum amyloid A: production by human white adipocyte and regulation by obesity and nutrition. Diabetologia 48, 519528.

24E Somm , P Cettour-Rose , C Asensio , (2006) Interleukin-1 receptor antagonist is upregulated during diet-induced obesity and regulates insulin sensitivity in rodents. Diabetologia 49, 387393.

25E Somm , E Henrichot , A Pernin , (2005) Decreased fat mass in interleukin-1 receptor antagonist-deficient mice: impact on adipogenesis, food intake, and energy expenditure. Diabetes 54, 35033509.

26CA Meier , E Bobbioni , C Gabay , (2002) IL-1 receptor antagonist serum levels are increased in human obesity: a possible link to the resistance to leptin? J Clin Endocrinol Metab 87, 11841188.

27MG Netea , LA Joosten , E Lewis , (2006) Deficiency of interleukin-18 in mice leads to hyperphagia, obesity and insulin resistance. Nat Med 12, 650656.

28T Skurk , H Kolb , S Muller-Scholze , (2005) The proatherogenic cytokine interleukin-18 is secreted by human adipocytes. Eur J Endocrinol 152, 863868.

29T Skurk , C berti-Huber , C Herder , (2007) Relationship between adipocyte size and adipokine expression and secretion. J Clin Endocrinol Metab 92, 10231033.

30M Straczkowski , I Kowalska , A Nikolajuk , (2007) Increased serum interleukin-18 concentration is associated with hypoadiponectinemia in obesity, independently of insulin resistance. Int J Obes (Lond) 31, 221225.

31R Cancello , C Henegar , N Viguerie , (2005) Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. Diabetes 54, 22772286.

33T Skurk , C Herder , I Kraft , (2005) Production and release of macrophage migration inhibitory factor from human adipocytes. Endocrinology 146, 10061011.

34M Straczkowski , S Dzienis-Straczkowska , A Stepien , (2002) Plasma interleukin-8 concentrations are increased in obese subjects and related to fat mass and tumor necrosis factor-alpha system. J Clin Endocrinol Metab 87, 46024606.

35M Straczkowski , I Kowalska , A Nikolajuk , (2003) Plasma interleukin 8 concentrations in obese subjects with impaired glucose tolerance. Cardiovasc Diabetol 2, 5.

36CA Curat , V Wegner , C Sengenes , (2006) Macrophages in human visceral adipose tissue: increased accumulation in obesity and a source of resistin and visfatin. Diabetologia 49, 744747.

37C Herder , H Hauner , K Kempf , (2007) Constitutive and regulated expression and secretion of interferon-gamma-inducible protein 10 (IP-10/CXCL10) in human adipocytes. Int J Obes (Lond) 31, 403410.

38JN Fain , DS Tichansky & AK Madan (2005) Transforming growth factor beta1 release by human adipose tissue is enhanced in obesity. Metabolism 54, 15461551.

39BG Gabrielsson , JM Johansson , M Lonn , (2003) High expression of complement components in omental adipose tissue in obese men. Obes Res 11, 699708.

40M Guerre-Millo (2006) Adipose tissue secretory function: implication in metabolic and cardiovascular complications of obesity. J Soc Biol 200, 3743.

41TE Graham , Q Yang , M Bluher , (2006) Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects. N Engl J Med 354, 25522563.

42Q Yang , TE Graham , N Mody , (2005) Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature 436, 356362.

43J Janke , S Engeli , M Boschmann , (2006) Retinol-binding protein 4 in human obesity. Diabetes 55, 28052810.

44VJ Carey , EE Walters , GA Colditz , (1997) Body fat distribution and risk of non-insulin-dependent diabetes mellitus in women. The Nurses’ Health Study. Am J Epidemiol 145, 614619.

45AH Kissebah , N Vydelingum , R Murray , (1982) Relation of body fat distribution to metabolic complications of obesity. J Clin Endocrinol Metab 54, 254260.

46M Visser , LM Bouter , GM McQuillan , (1999) Elevated C-reactive protein levels in overweight and obese adults. JAMA 282, 21312135.

47DG Cook , MA Mendall , PH Whincup , (2000) C-reactive protein concentration in children: relationship to adiposity and other cardiovascular risk factors. Atherosclerosis 149, 139150.

48JS Yudkin (2003) Adipose tissue, insulin action and vascular disease: inflammatory signals. Int J Obes Relat Metab Disord 27, Suppl. 3, S25S28.

49KE Wellen & GS Hotamisligil (2005) Inflammation, stress, and diabetes. J Clin Invest 115, 11111119.

50JP Despres & I Lemieux (2006) Abdominal obesity and metabolic syndrome. Nature 444, 881887.

51M Lafontan & J Girard (2008) Impact of visceral adipose tissue on liver metabolism. Part I: heterogeneity of adipose tissue and functional properties of visceral adipose tissue. Diabetes Metab 34, 317327.

52V van Harmelen , A Dicker , M Ryden , (2002) Increased lipolysis and decreased leptin production by human omental as compared with subcutaneous preadipocytes. Diabetes 51, 20292036.

53MC Alessi , D Bastelica , P Morange , (2000) Plasminogen activator inhibitor 1, transforming growth factor-beta1, and BMI are closely associated in human adipose tissue during morbid obesity. Diabetes 49, 13741380.

54JM Bruun , AS Lihn , AK Madan , (2004) Higher production of IL-8 in visceral vs. subcutaneous adipose tissue. Implication of nonadipose cells in adipose tissue. Am J Physiol Endocrinol Metab 286, E8E13.

55D Bastelica , P Morange , B Berthet , (2002) Stromal cells are the main plasminogen activator inhibitor-1-producing cells in human fat: evidence of differences between visceral and subcutaneous deposits. Arterioscler Thromb Vasc Biol 22, 173178.

56JN Fain , AK Madan , ML Hiler , (2004) Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans. Endocrinology 145, 22732282.

57H Hauner (2005) Secretory factors from human adipose tissue and their functional role. Proc Nutr Soc 64, 163169.

58CM de Souza Batista , RZ Yang , MJ Lee , (2007) Omentin plasma levels and gene expression are decreased in obesity. Diabetes 56, 16551661.

59P Arner (2006) Visfatin–a true or false trail to type 2 diabetes mellitus. J Clin Endocrinol Metab 91, 2830.

60SW Rabkin (2007) Epicardial fat: properties, function and relationship to obesity. Obes Rev 8, 253261.

61A Silaghi , MD Piercecchi-Marti , M Grino , (2008) Epicardial adipose tissue extent: relationship with age, body fat distribution, and coronaropathy. Obesity (Silver Spring) 16, 24242430.

62M Jernas , J Palming , K Sjoholm , (2006) Separation of human adipocytes by size: hypertrophic fat cells display distinct gene expression. FASEB J 20, 15401542.

63C Weyer , JE Foley , C Bogardus , (2000) Enlarged subcutaneous abdominal adipocyte size, but not obesity itself, predicts type II diabetes independent of insulin resistance. Diabetologia 43, 14981506.

64JN Fain (2006) Release of interleukins and other inflammatory cytokines by human adipose tissue is enhanced in obesity and primarily due to the nonfat cells. Vitam Horm 74, 443477.

65R Cancello , J Tordjman , C Poitou , (2006) Increased infiltration of macrophages in omental adipose tissue is associated with marked hepatic lesions in morbid human obesity. Diabetes 55, 15541561.

66SP Weisberg , D McCann , M Desai , (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112, 17961808.

67H Xu , GT Barnes , Q Yang , (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112, 18211830.

68C Henegar , J Tordjman , V Achard , (2008) Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity. Genome Biol 9, R14.

69U Kintscher , M Hartge , K Hess , (2008) T-lymphocyte infiltration in visceral adipose tissue: a primary event in adipose tissue inflammation and the development of obesity-mediated insulin resistance. Arterioscler Thromb Vasc Biol 28, 13041310.

70ME Rausch , S Weisberg , P Vardhana , (2008) Obesity in C57BL/6J mice is characterized by adipose tissue hypoxia and cytotoxic T-cell infiltration. Int J Obes (Lond) 32, 451463.

71H Wu , S Ghosh , XD Perrard , (2007) T-cell accumulation and regulated on activation, normal T cell expressed and secreted upregulation in adipose tissue in obesity. Circulation 115, 10291038.

72SR Bornstein , M Abu-Asab , A Glasow , (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.

74B Cousin , M Andre , L Casteilla , (2001) Altered macrophage-like functions of preadipocytes in inflammation and genetic obesity. J Cell Physiol 186, 380386.

75CN Lumeng , JL Bodzin & AR Saltiel (2007) Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 117, 175184.

76JM Olefsky & CK Glass (2010) Macrophages, inflammation, and insulin resistance. Annu Rev Physiol 72, 219246.

77K Karastergiou & V Mohamed-Ali (2010) The autocrine and paracrine roles of adipokines. Mol Cell Endocrinol 318, 6978.

78CA Curat , A Miranville , C Sengenes , (2004) From blood monocytes to adipose tissue-resident macrophages: induction of diapedesis by human mature adipocytes. Diabetes 53, 12851292.

80SP Weisberg , D Hunter , R Huber , (2006) CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J Clin Invest 116, 115124.

81KE Inouye , H Shi , JK Howard , (2007) Absence of CC chemokine ligand 2 does not limit obesity-associated infiltration of macrophages into adipose tissue. Diabetes 56, 22422250.

82P Trayhurn , B Wang & IS Wood (2008) Hypoxia in adipose tissue: a basis for the dysregulation of tissue function in obesity? Br J Nutr 100, 227235.

83M Guerre-Millo , A Grosfeld & T Issad (2002) Leptin is a hypoxia-inducible gene. Obes Res 10, 856858.

84S Cinti , G Mitchell , G Barbatelli , (2005) Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 46, 23472355.

85A Bouloumie , L Casteilla & M Lafontan (2008) Adipose tissue lymphocytes and macrophages in obesity and insulin resistance: makers or markers, and which comes first? Arterioscler Thromb Vasc Biol 28, 12111213.

86C Lagathu , JP Bastard , M Auclair , (2003) Chronic interleukin-6 (IL-6) treatment increased IL-6 secretion and induced insulin resistance in adipocyte: prevention by rosiglitazone. Biochem Biophys Res Commun 311, 372379.

87D Lacasa , S Taleb , M Keophiphath , (2007) Macrophage-secreted factors impair human adipogenesis: involvement of proinflammatory state in preadipocytes. Endocrinology 148, 868877.

88VA Constant , A Gagnon , A Landry , (2006) Macrophage-conditioned medium inhibits the differentiation of 3T3-L1 and human abdominal preadipocytes. Diabetologia 49, 14021411.

89PA Permana , C Menge & PD Reaven (2006) Macrophage-secreted factors induce adipocyte inflammation and insulin resistance. Biochem Biophys Res Commun 341, 507514.

90T Suganami , J Nishida & Y Ogawa (2005) A paracrine loop between adipocytes and macrophages aggravates inflammatory changes: role of free fatty acids and tumor necrosis factor alpha. Arterioscler Thromb Vasc Biol 25, 20622068.

91A Kumar , Y Takada , AM Boriek , (2004) Nuclear factor-kappaB: its role in health and disease. J Mol Med 82, 434448.

92ND Perkins (2007) Integrating cell-signalling pathways with NF-kappaB and IKK function. Nat Rev Mol Cell Biol 8, 4962.

93LH Sigal (2006) Basic science for the clinician 39: NF-kappaB-function, activation, control, and consequences. J Clin Rheumatol 12, 207211.

94E Maury & SM Brichard (2010) Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome. Mol Cell Endocrinol 314, 116.

95T Suganami , K Tanimoto-Koyama , J Nishida , (2007) Role of the Toll-like receptor 4/NF-kappaB pathway in saturated fatty acid-induced inflammatory changes in the interaction between adipocytes and macrophages. Arterioscler Thromb Vasc Biol 27, 8491.

96Y Lin , H Lee , AH Berg , (2000) The lipopolysaccharide-activated toll-like receptor (TLR)-4 induces synthesis of the closely related receptor TLR-2 in adipocytes. J Biol Chem 275, 2425524263.

97H Shi , MV Kokoeva , K Inouye , (2006) TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest 116, 30153025.

98Y Matsuzawa (2006) The metabolic syndrome and adipocytokines. FEBS Lett 580, 29172921.

99Y Matsuzawa (2006) Therapy insight: adipocytokines in metabolic syndrome and related cardiovascular disease. Nat Clin Pract Cardiovasc Med 3, 3542.

100H Chen (2006) Cellular inflammatory responses: novel insights for obesity and insulin resistance. Pharmacol Res 53, 469477.

101AE Malavazos , E Cereda , L Morricone , (2005) Monocyte chemoattractant protein 1: a possible link between visceral adipose tissue-associated inflammation and subclinical echocardiographic abnormalities in uncomplicated obesity. Eur J Endocrinol 153, 871877.

102AE Malavazos , MM Corsi , F Ermetici , (2007) Proinflammatory cytokines and cardiac abnormalities in uncomplicated obesity: relationship with abdominal fat deposition. Nutr Metab Cardiovasc Dis 17, 294302.

103N Ouchi , S Kihara , T Funahashi , (2003) Obesity, adiponectin and vascular inflammatory disease. Curr Opin Lipidol 14, 561566.

104C Herder , B Haastert , S Muller-Scholze , (2005) Association of systemic chemokine concentrations with impaired glucose tolerance and type 2 diabetes: results from the Cooperative Health Research in the Region of Augsburg Survey S4 (KORA S4). Diabetes 54, Suppl. 2, S11S17.

105FB Stentz , GE Umpierrez , R Cuervo , (2004) Proinflammatory cytokines, markers of cardiovascular risks, oxidative stress, and lipid peroxidation in patients with hyperglycemic crises. Diabetes 53, 20792086.

106C de Luca & JM Olefsky (2006) Stressed out about obesity and insulin resistance. Nat Med 12, 4142.

107I Harman-Boehm , M Bluher , H Redel , (2007) Macrophage infiltration into omental versus subcutaneous fat across different populations: effect of regional adiposity and the comorbidities of obesity. J Clin Endocrinol Metab 92, 22402247.

108AH Berg & PE Scherer (2005) Adipose tissue, inflammation, and cardiovascular disease. Circ Res 96, 939949.

109P Kopelman (2007) Health risks associated with overweight and obesity. Obes Rev 8, Suppl. 1, 1317.

110P Ziccardi , F Nappo , G Giugliano , (2002) Reduction of inflammatory cytokine concentrations and improvement of endothelial functions in obese women after weight loss over one year. Circulation 105, 804809.

111K Esposito , A Pontillo , C Di Palo , (2003) Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA 289, 17991804.

112LK Heilbronn & PM Clifton (2002) C-reactive protein and coronary artery disease: influence of obesity, caloric restriction and weight loss. J Nutr Biochem 13, 316321.

113JP Bastard , C Jardel , E Bruckert , (2000) Elevated levels of interleukin 6 are reduced in serum and subcutaneous adipose tissue of obese women after weight loss. J Clin Endocrinol Metab 85, 33383342.

114K Esposito , A Pontillo , M Ciotola , (2002) Weight loss reduces interleukin-18 levels in obese women. J Clin Endocrinol Metab 87, 38643866.

115JP Bastard , H Vidal , C Jardel , (2000) Subcutaneous adipose tissue expression of plasminogen activator inhibitor-1 gene during very low calorie diet in obese subjects. Int J Obes Relat Metab Disord 24, 7074.

116J Gomez-Ambrosi , J Salvador , F Rotellar , (2006) Increased serum amyloid A concentrations in morbid obesity decrease after gastric bypass. Obes Surg 16, 262269.

117S Taleb , R Cancello , C Poitou , (2006) Weight loss reduces adipose tissue cathepsin S and its circulating levels in morbidly obese women. J Clin Endocrinol Metab 91, 10421047.

119CW Kopp , HP Kopp , S Steiner , (2003) Weight loss reduces tissue factor in morbidly obese patients. Obes Res 11, 950956.

120TS Church , MS Willis , EL Priest , (2005) Obesity, macrophage migration inhibitory factor, and weight loss. Int J Obes (Lond) 29, 675681.

121T Christiansen , B Richelsen & JM Bruun (2005) Monocyte chemoattractant protein-1 is produced in isolated adipocytes, associated with adiposity and reduced after weight loss in morbid obese subjects. Int J Obes (Lond) 29, 146150.

122AR Vasudevan , H Wu , AM Xydakis , (2006) Eotaxin and obesity. J Clin Endocrinol Metab 91, 256261.

123K Krzyzanowska , F Mittermayer , W Krugluger , (2006) Increase in visfatin after weight loss induced by gastroplastic surgery. Obesity (Silver Spring) 14, 18861889.

124JP Bastard , B Hainque , E Dusserre , (1999) Peroxisome proliferator activated receptor-gamma, leptin and tumor necrosis factor-alpha mRNA expression during very low calorie diet in subcutaneous adipose tissue in obese women. Diabetes Metab Res Rev 15, 9298.

125HP Kopp , CW Kopp , A Festa , (2003) Impact of weight loss on inflammatory proteins and their association with the insulin resistance syndrome in morbidly obese patients. Arterioscler Thromb Vasc Biol 23, 10421047.

126C Poitou , C Coussieu , C Rouault , (2006) Serum amyloid A: a marker of adiposity-induced low-grade inflammation but not of metabolic status. Obesity (Silver Spring) 14, 309318.

127K Clement , N Viguerie , C Poitou , (2004) Weight loss regulates inflammation-related genes in white adipose tissue of obese subjects. FASEB J 18, 16571669.

128C de Luca & JM Olefsky (2008) Inflammation and insulin resistance. FEBS Lett 582, 97105.

129L Li , M Naples , H Song , (2007) LCAT-null mice develop improved hepatic insulin sensitivity through altered regulation of transcription factors and suppressors of cytokine signaling. Am J Physiol Endocrinol Metab 293, E587E594.

130HL Rui , E Fan , HM Zhou , (2002) SUMO-1 modification of the C-terminal KVEKVD of Axin is required for JNK activation but has no effect on Wnt signaling. J Biol Chem 277, 4298142986.

131K Ueki , T Kondo & CR Kahn (2004) Suppressor of cytokine signaling 1 (SOCS-1) and SOCS-3 cause insulin resistance through inhibition of tyrosine phosphorylation of insulin receptor substrate proteins by discrete mechanisms. Mol Cell Biol 24, 54345446.

132JH Kim , JE Kim , HY Liu , (2008) Regulation of interleukin-6-induced hepatic insulin resistance by mammalian target of rapamycin through the STAT3-SOCS3 pathway. J Biol Chem 283, 708715.

133CH Lang , C Dobrescu & GJ Bagby (1992) Tumor necrosis factor impairs insulin action on peripheral glucose disposal and hepatic glucose output. Endocrinology 130, 4352.

134PD Miles , OM Romeo , K Higo , (1997) TNF-alpha-induced insulin resistance in vivo and its prevention by troglitazone. Diabetes 46, 16781683.

135T Atsumi , YR Cho , L Leng , (2007) The proinflammatory cytokine macrophage migration inhibitory factor regulates glucose metabolism during systemic inflammation. J Immunol 179, 53995406.

136N Houstis , ED Rosen & ES Lander (2006) Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature 440, 944948.

137T Nishikawa , D Kukidome , K Sonoda , (2007) Impact of mitochondrial ROS production in the pathogenesis of insulin resistance. Diabetes Res Clin Pract 77, Suppl. 1, S161S164.

138Y Li , C Jiang , G Xu , (2008) Homocysteine upregulates resistin production from adipocytes in vivo and in vitro. Diabetes 57, 817827.

139P Arner (2005) Insulin resistance in type 2 diabetes – role of the adipokines. Curr Mol Med 5, 333339.

140SF Yan , GR Barile , V D'Agati , (2007) The biology of RAGE and its ligands: uncovering mechanisms at the heart of diabetes and its complications. Curr Diab Rep 7, 146153.

141T Nomiyama , D Perez-Tilve , D Ogawa , (2007) Osteopontin mediates obesity-induced adipose tissue macrophage infiltration and insulin resistance in mice. J Clin Invest 117, 28772888.

142K Clement & D Langin (2007) Regulation of inflammation-related genes in human adipose tissue. J Intern Med 262, 422430.

143JK Kim , YJ Kim , JJ Fillmore , (2001) Prevention of fat-induced insulin resistance by salicylate. J Clin Invest 108, 437446.

145SE Shoelson , J Lee & M Yuan (2003) Inflammation and the IKK beta/I kappa B/NF-kappa B axis in obesity- and diet-induced insulin resistance. Int J Obes Relat Metab Disord 27, Suppl. 3, S49S52.

146A Fleischman , SE Shoelson , R Bernier , (2008) Salsalate improves glycemia and inflammatory parameters in obese young adults. Diabetes Care 31, 289294.

147MC Wasko , HB Hubert , VB Lingala , (2007) Hydroxychloroquine and risk of diabetes in patients with rheumatoid arthritis. JAMA 298, 187193.

148CM Larsen , M Faulenbach , A Vaag , (2007) Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med 356, 15171526.

149R Barbuio , M Milanski , MB Bertolo , (2007) Infliximab reverses steatosis and improves insulin signal transduction in liver of rats fed a high-fat diet. J Endocrinol 194, 539550.

150H Dominguez , H Storgaard , C Rask-Madsen , (2005) Metabolic and vascular effects of tumor necrosis factor-alpha blockade with etanercept in obese patients with type 2 diabetes. J Vasc Res 42, 517525.

151LS Tam , B Tomlinson , TT Chu , (2007) Impact of TNF inhibition on insulin resistance and lipids levels in patients with rheumatoid arthritis. Clin Rheumatol 26, 14951498.

152P Di Rocco , M Manco , G Rosa , (2004) Lowered tumor necrosis factor receptors, but not increased insulin sensitivity, with infliximab. Obes Res 12, 734739.

153SE Borst , Y Lee , CF Conover , (2004) Neutralization of tumor necrosis factor-alpha reverses insulin resistance in skeletal muscle but not adipose tissue. Am J Physiol Endocrinol Metab 287, E934E938.

156DS Bell , JH O'Keefe & P Jellinger (2008) Postprandial dysmetabolism: the missing link between diabetes and cardiovascular events? Endocr Pract 14, 112124.

157JH O'Keefe , NM Gheewala & JO O'Keefe (2008) Dietary strategies for improving post-prandial glucose, lipids, inflammation, and cardiovascular health. J Am Coll Cardiol 51, 249255.

158M Napolitano & E Bravo (2005) Lipid metabolism and TNF-alpha secretion in response to dietary sterols in human monocyte derived macrophages. Eur J Clin Invest 35, 482490.

159AJ van Oostrom , TP Sijmonsma , C Verseyden , (2003) Postprandial recruitment of neutrophils may contribute to endothelial dysfunction. J Lipid Res 44, 576583.

161A Alipour , AJ van Oostrom , A Izraeljan , (2008) Leukocyte activation by triglyceride-rich lipoproteins. Arterioscler Thromb Vasc Biol 28, 792797.

162GC Burdge & PC Calder (2005) Plasma cytokine response during the postprandial period: a potential causal process in vascular disease? Br J Nutr 93, 39.

163PJ Manning , WH Sutherland , MM McGrath , (2008) Postprandial cytokine concentrations and meal composition in obese and lean women. Obesity (Silver Spring) 16, 20462052.

164A Jellema , J Plat & RP Mensink (2004) Weight reduction, but not a moderate intake of fish oil, lowers concentrations of inflammatory markers and PAI-1 antigen in obese men during the fasting and postprandial state. Eur J Clin Invest 34, 766773.

165K Esposito , M Ciotola , FC Sasso , (2007) Effect of a single high-fat meal on endothelial function in patients with the metabolic syndrome: role of tumor necrosis factor-alpha. Nutr Metab Cardiovasc Dis 17, 274279.

166F Nappo , K Esposito , M Cioffi , (2002) Postprandial endothelial activation in healthy subjects and in type 2 diabetic patients: role of fat and carbohydrate meals. J Am Coll Cardiol 39, 11451150.

167A Ceriello , R Assaloni , RR Da , (2005) Effect of atorvastatin and irbesartan, alone and in combination, on postprandial endothelial dysfunction, oxidative stress, and inflammation in type 2 diabetic patients. Circulation 111, 25182524.

169A Ceriello , N Bortolotti , E Motz , (1998) Meal-generated oxidative stress in type 2 diabetic patients. Diabetes Care 21, 15291533.

170KE Wellen , R Fucho , MF Gregor , (2007) Coordinated regulation of nutrient and inflammatory responses by STAMP2 is essential for metabolic homeostasis. Cell 129, 537548.

171A Abedini & SE Shoelson (2007) Inflammation and obesity: STAMPing out insulin resistance? Immunol Cell Biol 85, 399400.

172G Candore , G Colonna-Romano , CR Balistreri , (2006) Biology of longevity: role of the innate immune system. Rejuvenation Res 9, 143148.

173KS Krabbe , M Pedersen & H Bruunsgaard (2004) Inflammatory mediators in the elderly. Exp Gerontol 39, 687699.

174J Wei , H Xu , JL Davies , (1992) Increase of plasma IL-6 concentration with age in healthy subjects. Life Sci 51, 19531956.