Inflammation, Adiposity, and Atherogenic Dyslipidemia in Rheumatoid Arthritis: Is There a Paradoxical Relationship?

Part of the following topical collections:
  1. Topical Collection on Autoimmunity


Dyslipidemia is highly prevalent in rheumatoid arthritis (RA) and appears to be present very early in the RA disease process, in some studies even before a diagnosis of clinical RA has been made. The association between lipid measures and the risk of cardiovascular disease (CVD) in RA appears to be paradoxical, whereby lower levels of total cholesterol (TC), low-density lipoprotein (LDL-C), and atherogenic ratios are associated with higher CVD risk. This may be due to the lipid-lowering effects of RA-related systemic inflammation. Therefore, standard CVD risk calculators have been shown to underperform in RA. Data also suggest that lipoprotein particle sizes and the apolipoprotein cargo of lipoproteins skew toward atherogenic dyslipidemia in RA and may contribute to the initiation and progression of atherosclerosis. Inflammatory burden in RA may also alter the anti-inflammatory and atheroprotective roles associated with high-density lipoprotein cholesterol (HDL-C). Adipose tissue is quantitatively increased in RA patients compared with matched non-RA controls and may be more inflamed and metabolically dysfunctional compared with an otherwise similar non-RA patient. In vitro, animal, and a handful of non-RA human, studies suggest that inflamed, metabolically dysfunctional adipose tissue contributes directly to lower HDL-C levels. In turn, lower HDL-C that has been altered functionally by inflammation may lead to expanded adipose mass and further adipose dysfunction and inflammation. In the last part of this review, we speculate how the RA disease state may recapitulate these processes.


Lipids Lipoproteins Pro-inflammatory HDL Adipose inflammation Cardiovascular Risk prediction Atherosclerosis 


Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Gabriel SE, Crowson CS, O’Fallon WM. The epidemiology of rheumatoid arthritis in Rochester, Minnesota, 1955–1985. Arthritis Rheum. 1999;42:415–20.PubMedCrossRefGoogle Scholar
  2. 2.
    Wolfe F. Comparative usefulness of c-reactive protein and erythrocyte sedimentation rate in patients with rheumatoid arthritis. J Rheumatol. 1997;24:1477–85.PubMedGoogle Scholar
  3. 3.
    Sokolove J, Bromberg R, Deane KD, Lahey LJ, Derber LA, Chandra PE, et al. Autoantibody epitope spreading in the pre-clinical phase predicts progression to rheumatoid arthritis. PLoS One. 2012;7:e35296.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Mutru O, Laakso M, Isomaki H, Koota K. Cardiovascular mortality in patients with rheumatoid-arthritis. Cardiology. 1989;76:71–7.PubMedCrossRefGoogle Scholar
  5. 5.
    Gabriel SE, Crowson CS, O’Fallon WM. Mortality in rheumatoid arthritis: have we made an impact in 4 decades? J Rheumatol. 1999;26:2529–33.PubMedGoogle Scholar
  6. 6.
    Avina-Zubieta JA, Choi HK, Sadatsafavi M, Etminan M, Esdaile JM, Lacaille D. Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum. 2008;59:1690–7.PubMedCrossRefGoogle Scholar
  7. 7.
    Wolfe F, Mitchell DM, Sibley JT, Fries JF, Bloch DA, Williams CA, et al. The mortality of rheumatoid arthritis. Arthritis Rheum. 1994;37:481–94.PubMedCrossRefGoogle Scholar
  8. 8.
    Gonzalez A, Maradit Kremers H, Crowson CS, Nicola PJ, Davis 3rd JM, Therneau TM, et al. The widening mortality gap between rheumatoid arthritis patients and the general population. Arthritis Rheum. 2007;56:3583–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Matheny M, McPheeters ML, Glasser A, Mercaldo N, Weaver RB, Jerome RN, Walden R, McKoy JN, Pritchett J, Tsai C. Systematic review of cardiovascular disease risk assessment tools. Rockville (MD); 2011.Google Scholar
  10. 10.
    Cook NR, Paynter NP, Eaton CB, Manson JE, Martin LW, Robinson JG, et al. Comparison of the Framingham and Reynolds Risk Scores for global cardiovascular risk prediction in the multiethnic women’s health initiative. Circulation. 2012;125:1748–56. S1741–1711.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Crowson CS, Matteson EL, Roger VL, Therneau TM, Gabriel SE. Usefulness of risk scores to estimate the risk of cardiovascular disease in patients with rheumatoid arthritis. Am J Cardiol. 2012;110:420–4.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Arts EE, Popa C, Den Broeder AA, Semb AG, Toms T, Kitas GD, van Riel PL, Fransen J. Performance of four current risk algorithms in predicting cardiovascular events in patients with early rheumatoid arthritis. Ann Rheum Dis. 2014.Google Scholar
  13. 13.
    Ohta H, Wada H, Niwa T, Kirii H, Iwamoto N, Fujii H, et al. Disruption of tumor necrosis factor-alpha gene diminishes the development of atherosclerosis in ApoE-deficient mice. Atherosclerosis. 2005;180:11–7.PubMedCrossRefGoogle Scholar
  14. 14.
    Isomaa B, Almgren P, Tuomi T, Forsen B, Lahti K, Nissen M, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care. 2001;24:683–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Mooradian AD, Haas MJ, Wehmeier KR, Wong NC. Obesity-related changes in high-density lipoprotein metabolism. Obesity. 2008;16:1152–60.PubMedCrossRefGoogle Scholar
  16. 16.
    McGillicuddy FC, Reilly MP, Rader DJ. Adipose modulation of high-density lipoprotein cholesterol: implications for obesity, high-density lipoprotein metabolism, and cardiovascular disease. Circulation. 2011;124:1602–5.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Giles JT, Ling SM, Ferrucci L, Bartlett SJ, Andersen RE, Towns M, et al. Abnormal body composition phenotypes in older rheumatoid arthritis patients: association with disease characteristics and pharmacotherapies. Arthritis Rheum. 2008;59:807–15.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.•
    Giles JT, Allison M, Blumenthal RS, Post W, Gelber AC, Petri M, et al. Abdominal adiposity in rheumatoid arthritis: association with cardiometabolic risk factors and disease characteristics. Arthritis Rheum. 2010;62:3173–82. The researchers show that elevated visceral fat was associated with a significantly higher adjusted probability of having an elevated fasting glucose, hypertension, or the composite definition of the metabolic syndrome for the RA group compared with controls.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Kramer HR, Fontaine KR, Bathon JM, Giles JT. Muscle density in rheumatoid arthritis: associations with disease features and functional outcomes. Arthritis Rheum. 2012;64:2438–50.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    de Haan W, Bhattacharjee A, Ruddle P, Kang MH, Hayden MR. ABCA1 in adipocytes regulates adipose tissue lipid content, glucose tolerance, and insulin sensitivity. J Lipid Res. 2014;55:516–23.PubMedCrossRefGoogle Scholar
  21. 21.
    Wei H, Averill MM, McMillen TS, Dastvan F, Mitra P, Subramanian S, et al. Modulation of adipose tissue lipolysis and body weight by high-density lipoproteins in mice. Nutr Diabetes. 2014;4:e108.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Umemoto T, Han CY, Mitra P, Averill MM, Tang C, Goodspeed L, et al. Apolipoprotein AI and high-density lipoprotein have anti-inflammatory effects on adipocytes via cholesterol transporters: ATP-binding cassette A-1, ATP-binding cassette G-1, and scavenger receptor B-1. Circ Res. 2013;112:1345–54.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Arsenault BJ, Boekholdt SM, Kastelein JJ. Lipid parameters for measuring risk of cardiovascular disease. Nat Rev Cardiol. 2011;8:197–206.PubMedCrossRefGoogle Scholar
  24. 24.
    Batsis JA, Lopez-Jimenez F. Cardiovascular risk assessment—from individual risk prediction to estimation of global risk and change in risk in the population. BMC Med. 2010;8:29.PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Nikolic D, Katsiki N, Montalto G, Isenovic ER, Mikhailidis DP, Rizzo M. Lipoprotein subfractions in metabolic syndrome and obesity: clinical significance and therapeutic approaches. Nutrients. 2013;5:928–48.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Yang CY, Raya JL, Chen HH, Chen CH, Abe Y, Pownall HJ, et al. Isolation, characterization, and functional assessment of oxidatively modified subfractions of circulating low-density lipoproteins. Arterioscler Thromb Vasc Biol. 2003;23:1083–90.PubMedCrossRefGoogle Scholar
  27. 27.
    Lamarche B, Tchernof A, Moorjani S, Cantin B, Dagenais GR, Lupien PJ, et al. Small, dense low-density lipoprotein particles as a predictor of the risk of ischemic heart disease in men. Prospective results from the Quebec cardiovascular study. Circulation. 1997;95:69–75.PubMedCrossRefGoogle Scholar
  28. 28.•
    Mineo C, Shaul PW. Novel biological functions of high-density lipoprotein cholesterol. Circ Res. 2012;111:1079–90. This review article summarizes how in addition to size, the protein cargo of the HDL particle plays a role in cholesterol efflux capacity, anti-inflammatory function, and anti-oxidant capabilities.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Bansal S, Buring JE, Rifai N, Mora S, Sacks FM, Ridker PM. Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. JAMA. 2007;298:309–16.PubMedCrossRefGoogle Scholar
  30. 30.
    Sattar N, Packard CJ, Petrie JR. The end of triglycerides in cardiovascular risk assessment? Rumours of death are greatly exaggerated. Bmj. 1998;317:553–4.PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Contois JH, McConnell JP, Sethi AA, Csako G, Devaraj S, Hoefner DM, et al. Apolipoprotein B and cardiovascular disease risk: position statement from the AACC Lipoproteins and Vascular Diseases Division Working Group on Best Practices. Clin Chem. 2009;55:407–19.PubMedCrossRefGoogle Scholar
  32. 32.
    Lipoproteins A, Vascular Diseases Division Working Group on Best P, Cole TG, Contois JH, Csako G, McConnell JP, et al. Association of apolipoprotein B and nuclear magnetic resonance spectroscopy-derived LDL particle number with outcomes in 25 clinical studies: assessment by the AACC Lipoprotein and Vascular Diseases Division Working Group on Best Practices. Clin Chem. 2013;59:752–70.CrossRefGoogle Scholar
  33. 33.
    Alaupovic P. The concept of apolipoprotein-defined lipoprotein families and its clinical significance. Curr Atheroscler Rep. 2003;5:459–67.PubMedCrossRefGoogle Scholar
  34. 34.
    Wang CS, McConathy WJ, Kloer HU, Alaupovic P. Modulation of lipoprotein lipase activity by apolipoproteins. Effect of apolipoprotein C-III. J Clin Invest. 1985;75:384–90.PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Clavey V, Lestavel-Delattre S, Copin C, Bard JM, Fruchart JC. Modulation of lipoprotein B binding to the LDL receptor by exogenous lipids and apolipoproteins CI, CII, CIII, and E. Arterioscler Thromb Vasc Biol. 1995;15:963–71.PubMedCrossRefGoogle Scholar
  36. 36.
    Florez H, Mendez A, Casanova-Romero P, Larreal-Urdaneta C, Castillo-Florez S, Lee D, et al. Increased apolipoprotein C-III levels associated with insulin resistance contribute to dyslipidemia in normoglycemic and diabetic subjects from a triethnic population. Atherosclerosis. 2006;188:134–41.PubMedCrossRefGoogle Scholar
  37. 37.
    Knowlton N, Wages JA, Centola MB, Giles J, Bathon J, Quiroga C, et al. Apolipoprotein B-containing lipoprotein subclasses as risk factors for cardiovascular disease in patients with rheumatoid arthritis. Arthritis Care Res (Hoboken). 2012;64:993–1000.CrossRefGoogle Scholar
  38. 38.
    Lee SJ, Campos H, Moye LA, Sacks FM. LDL containing apolipoprotein CIII is an independent risk factor for coronary events in diabetic patients. Arterioscler Thromb Vasc Biol. 2003;23:853–8.PubMedCrossRefGoogle Scholar
  39. 39.
    Dessein PH, Joffe BI, Veller MG, Stevens BA, Tobias M, Reddi K, et al. Traditional and nontraditional cardiovascular risk factors are associated with atherosclerosis in rheumatoid arthritis. J Rheumatol. 2005;32:435–42.PubMedGoogle Scholar
  40. 40.
    Kavanaugh A. Dyslipoproteinaemia in a subset of patients with rheumatoid arthritis. Ann Rheum Dis. 1994;53:551–2.PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    van Halm VP, Nielen MM, Nurmohamed MT, van Schaardenburg D, Reesink HW, Voskuyl AE, et al. Lipids and inflammation: serial measurements of the lipid profile of blood donors who later developed rheumatoid arthritis. Ann Rheum Dis. 2007;66:184–8.PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.•
    Myasoedova E, Crowson CS, Kremers HM, Fitz-Gibbon PD, Therneau TM, Gabriel SE. Total cholesterol and LDL levels decrease before rheumatoid arthritis. Ann Rheum Dis. 2010;69:1310–4. In this population-based RA incidence cohort, it has been shown that in RA patients, CVD risk in relation to total cholesterol and LDL levels could potentially be represented by a U-shaped curve. This pattern reflects the ‘lipid paradox’ in RA, with increased CVD risk in patients with active disease despite reduced serum cholesterol levels compared with the general population.PubMedCentralPubMedCrossRefGoogle Scholar
  43. 43.
    Toms TE, Panoulas VF, Douglas KM, Nightingale P, Smith JP, Griffiths H, et al. Are lipid ratios less susceptible to change with systemic inflammation than individual lipid components in patients with rheumatoid arthritis? Angiology. 2011;62:167–75.PubMedCrossRefGoogle Scholar
  44. 44.
    Liao KP, Cai T, Gainer VS, Cagan A, Murphy SN, Liu C, et al. Lipid and lipoprotein levels and trend in rheumatoid arthritis compared to the general population. Arthritis Care Res (Hoboken). 2013;65:2046–50.CrossRefGoogle Scholar
  45. 45.
    Choi HK, Seeger JD. Lipid profiles among US elderly with untreated rheumatoid arthritis—the Third National Health and Nutrition Examination Survey. J Rheumatol. 2005;32:2311–6.PubMedGoogle Scholar
  46. 46.
    Wallberg-Jonsson S, Ohman M, Rantapaa-Dahlqvist S. Which factors are related to the presence of atherosclerosis in rheumatoid arthritis? Scand J Rheumatol. 2004;33:373–9.PubMedCrossRefGoogle Scholar
  47. 47.
    Semb AG, Kvien TK, Aastveit AH, Jungner I, Pedersen TR, Walldius G, et al. Lipids, myocardial infarction and ischaemic stroke in patients with rheumatoid arthritis in the Apolipoprotein-related MOrtality RISk (AMORIS) Study. Ann Rheum Dis. 2010;69:1996–2001.PubMedCrossRefGoogle Scholar
  48. 48.
    Gonzalez A, Maradit Kremers H, Crowson CS, Ballman KV, Roger VL, Jacobsen SJ, et al. Do cardiovascular risk factors confer the same risk for cardiovascular outcomes in rheumatoid arthritis patients as in non-rheumatoid arthritis patients? Ann Rheum Dis. 2008;67:64–9.PubMedCrossRefGoogle Scholar
  49. 49.•
    Zhang J, Chen L, Delzell E, Muntner P, Hillegass WB, Safford MM, et al. The association between inflammatory markers, serum lipids and the risk of cardiovascular events in patients with rheumatoid arthritis. Ann Rheum Dis. 2014;73:1301–8. This large, retrospective cohort study provides evidence supporting the hypothesis that RA-related systemic inflammation plays a role in cardiovascular risk and also in the intricate relationship between LDL and cardiovascular risk in RA patients.PubMedCrossRefGoogle Scholar
  50. 50.
    Myasoedova E, Crowson CS, Kremers HM, Roger VL, Fitz-Gibbon PD, Therneau TM, et al. Lipid paradox in rheumatoid arthritis: the impact of serum lipid measures and systemic inflammation on the risk of cardiovascular disease. Ann Rheum Dis. 2011;70:482–7.PubMedCentralPubMedCrossRefGoogle Scholar
  51. 51.
    Rauchhaus M, Clark AL, Doehner W, Davos C, Bolger A, Sharma R, et al. The relationship between cholesterol and survival in patients with chronic heart failure. J Am Coll Cardiol. 2003;42:1933–40.PubMedCrossRefGoogle Scholar
  52. 52.
    Carmena R, Duriez P, Fruchart JC. Atherogenic lipoprotein particles in atherosclerosis. Circulation. 2004;109:III2–7.PubMedCrossRefGoogle Scholar
  53. 53.
    Chung CP, Oeser A, Raggi P, Sokka T, Pincus T, Solus JF, et al. Lipoprotein subclasses determined by nuclear magnetic resonance spectroscopy and coronary atherosclerosis in patients with rheumatoid arthritis. J Rheumatol. 2010;37:1633–8.PubMedCentralPubMedCrossRefGoogle Scholar
  54. 54.
    Arts E, Fransen J, Lemmers H, Stalenhoef A, Joosten L, van Riel P, et al. High-density lipoprotein cholesterol subfractions HDL2 and HDL3 are reduced in women with rheumatoid arthritis and may augment the cardiovascular risk of women with ra: a cross-sectional study. Arthritis Res Ther. 2012;14:R116.PubMedCentralPubMedCrossRefGoogle Scholar
  55. 55.
    Hurt-Camejo E, Paredes S, Masana L, Camejo G, Sartipy P, Rosengren B, et al. Elevated levels of small, low-density lipoprotein with high affinity for arterial matrix components in patients with rheumatoid arthritis: possible contribution of phospholipase A2 to this atherogenic profile. Arthritis Rheum. 2001;44:2761–7.PubMedCrossRefGoogle Scholar
  56. 56.
    Park YB, Lee SK, Lee WK, Suh CH, Lee CW, Lee CH, et al. Lipid profiles in untreated patients with rheumatoid arthritis. J Rheumatol. 1999;26:1701–4.PubMedGoogle Scholar
  57. 57.
    Ajeganova S, Ehrnfelt C, Alizadeh R, Rohani M, Jogestrand T, Hafstrom I, et al. Longitudinal levels of apolipoproteins and antibodies against phosphorylcholine are independently associated with carotid artery atherosclerosis 5 years after rheumatoid arthritis onset—a prospective cohort study. Rheumatology (Oxford). 2011;50:1785–93.CrossRefGoogle Scholar
  58. 58.
    Ohman M, Ohman ML, Wallberg-Jonsson S. The ApoB/ApoA1 ratio predicts future cardiovascular events in patients with rheumatoid arthritis. Scand J Rheumatol. 2014;43:259–64.PubMedCrossRefGoogle Scholar
  59. 59.•
    Robertson J, Peters MJ, McInnes IB, Sattar N. Changes in lipid levels with inflammation and therapy in ra: a maturing paradigm. Nature Rev Rheumatol. 2013;9:513–23. This article provides an up-to-date review of the literature on the effects of anti-inflammatory therapies on lipid levels in RA patients.CrossRefGoogle Scholar
  60. 60.
    Steiner G, Urowitz MB. Lipid profiles in patients with rheumatoid arthritis: mechanisms and the impact of treatment. Semin Arthritis Rheum. 2009;38:372–81.PubMedCrossRefGoogle Scholar
  61. 61.
    Kerekes G, Soltesz P, Der H, Veres K, Szabo Z, Vegvari A, et al. Effects of rituximab treatment on endothelial dysfunction, carotid atherosclerosis, and lipid profile in rheumatoid arthritis. Clin Rheumatol. 2009;28:705–10.PubMedCrossRefGoogle Scholar
  62. 62.
    Company B-MS. Briefing document for abatacept (bms-188667). 2005:FDA BIOLOGICAL LICENSE APPLICATION 125118.Google Scholar
  63. 63.
    McInnes IB, Thompson L, Giles JT, Bathon JM, Salmon JE, Beaulieu AD, Codding CE, Carlson TH, Delles C, Lee JS, Sattar N. Effect of interleukin-6 receptor blockade on surrogates of vascular risk in rheumatoid arthritis: Measure, a randomised, placebo-controlled study. Ann Rheum Dis. 2013Google Scholar
  64. 64.
    Rao VU, Pavlov A, Klearman M, Musselman D, Giles JT, Bathon JM, Sattar N, Lee JS. An evaluation of risk factors for major adverse cardiovascular events during tocilizumab therapy. Arthritis Rheum. 2014. doi:10.1002/art.38920.
  65. 65.
    Alvarez C, Ramos A. Lipids, lipoproteins, and apoproteins in serum during infection. Clin Chem. 1986;32:142–5.PubMedGoogle Scholar
  66. 66.
    Karabina SA, Brocheriou I, Le Naour G, Agrapart M, Durand H, Gelb M, et al. Atherogenic properties of LDL particles modified by human group X secreted phospholipase A2 on human endothelial cell function. FASEB J: Off Publ Fed Am Soc Exp Biol. 2006;20:2547–9.CrossRefGoogle Scholar
  67. 67.
    Hurt-Camejo E, Camejo G, Sartipy P. Phospholipase A2 and small, dense low-density lipoprotein. Curr Opin Lipidol. 2000;11:465–71.PubMedCrossRefGoogle Scholar
  68. 68.
    Van Lenten BJ, Reddy ST, Navab M, Fogelman AM. Understanding changes in high density lipoproteins during the acute phase response. Arterioscler Thromb Vasc Biol. 2006;26:1687–8.PubMedCrossRefGoogle Scholar
  69. 69.
    Navab M, Anantharamaiah GM, Reddy ST, Van Lenten BJ, Ansell BJ, Fogelman AM. Mechanisms of disease: proatherogenic HDL—an evolving field. Nature Clin Pract Endocrinol Metab. 2006;2:504–11.CrossRefGoogle Scholar
  70. 70.
    Navab M, Berliner JA, Subbanagounder G, Hama S, Lusis AJ, Castellani LW, et al. HDL and the inflammatory response induced by LDL-derived oxidized phospholipids. Arterioscler Thromb Vasc Biol. 2001;21:481–8.PubMedCrossRefGoogle Scholar
  71. 71.
    Hima Bindu G, Rao VS, Kakkar VV. Friend turns foe: transformation of anti-inflammatory HDL to proinflammatory HDL during acute-phase response. Cholesterol. 2011;2011:274629.Google Scholar
  72. 72.
    McMahon M, Grossman J, FitzGerald J, Dahlin-Lee E, Wallace DJ, Thong BY, et al. Proinflammatory high-density lipoprotein as a biomarker for atherosclerosis in patients with systemic lupus erythematosus and rheumatoid arthritis. Arthritis Rheum. 2006;54:2541–9.PubMedCrossRefGoogle Scholar
  73. 73.
    Sammalkorpi K, Valtonen V, Kerttula Y, Nikkila E, Taskinen MR. Changes in serum lipoprotein pattern induced by acute infections. Metabolism. 1988;37:859–65.PubMedCrossRefGoogle Scholar
  74. 74.
    Akgun S, Ertel NH, Mosenthal A, Oser W. Postsurgical reduction of serum lipoproteins: interleukin-6 and the acute-phase response. J Lab Clin Med. 1998;131:103–8.PubMedCrossRefGoogle Scholar
  75. 75.
    Phillips GB, Jing T, Heymsfield SB. Relationships in men of sex hormones, insulin, adiposity, and risk factors for myocardial infarction. Metab Clin Exp. 2003;52:784–90.PubMedCrossRefGoogle Scholar
  76. 76.
    Lakka HM, Lakka TA, Tuomilehto J, Salonen JT. Abdominal obesity is associated with increased risk of acute coronary events in men. Eur Heart J. 2002;23:706–13.PubMedCrossRefGoogle Scholar
  77. 77.
    Shuman WP, Morris LL, Leonetti DL, Wahl PW, Moceri VM, Moss AA, et al. Abnormal body fat distribution detected by computed tomography in diabetic men. Investig Radiol. 1986;21:483–7.CrossRefGoogle Scholar
  78. 78.
    Ortega Martinez de Victoria E, Xu X, Koska J, Francisco AM, Scalise M, Ferrante Jr AW, et al. Macrophage content in subcutaneous adipose tissue: associations with adiposity, age, inflammatory markers, and whole-body insulin action in healthy Pima Indians. Diabetes. 2009;58:385–93.PubMedCentralPubMedCrossRefGoogle Scholar
  79. 79.
    Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante Jr AW. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Investig. 2003;112:1796–808.PubMedCentralPubMedCrossRefGoogle Scholar
  80. 80.
    Baeten D, Boots AM, Steenbakkers PG, Elewaut D, Bos E, Verheijden GF, et al. Human cartilage gp-39+, CD16+ monocytes in peripheral blood and synovium: correlation with joint destruction in rheumatoid arthritis. Arthritis Rheum. 2000;43:1233–43.PubMedCrossRefGoogle Scholar
  81. 81.
    Valledor AF, Comalada M, Santamaria-Babi LF, Lloberas J, Celada A. Macrophage proinflammatory activation and deactivation: a question of balance. Adv Immunol. 2010;108:1–20.PubMedCrossRefGoogle Scholar
  82. 82.
    Duff GW. Cytokines and acute phase proteins in rheumatoid arthritis. Scand J Rheumatol Suppl. 1994;100:9–19.PubMedCrossRefGoogle Scholar
  83. 83.
    Maruotti N, Grano M, Colucci S, d’Onofrio F, Cantatore FP. Osteoclastogenesis and arthritis. Clin Exp Med. 2011;11:137–45.PubMedCrossRefGoogle Scholar
  84. 84.
    Yu R, Kim CS, Kwon BS, Kawada T. Mesenteric adipose tissue-derived monocyte chemoattractant protein-1 plays a crucial role in adipose tissue macrophage migration and activation in obese mice. Obesity. 2006;14:1353–62.PubMedCrossRefGoogle Scholar
  85. 85.
    Dusserre E, Moulin P, Vidal H. Differences in mRNA expression of the proteins secreted by the adipocytes in human subcutaneous and visceral adipose tissues. Biochim Biophys Acta. 2000;1500:88–96.PubMedCrossRefGoogle Scholar
  86. 86.
    Fontana L, Eagon JC, Trujillo ME, Scherer PE, Klein S. Visceral fat adipokine secretion is associated with systemic inflammation in obese humans. Diabetes. 2007;56:1010–3.PubMedCrossRefGoogle Scholar
  87. 87.
    Martinez-Santibanez G, Lumeng CN. Macrophages and the regulation of adipose tissue remodeling. Annu Rev Nutr. 2014;34:57–76.PubMedCrossRefGoogle Scholar
  88. 88.
    Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993;259:87–91.PubMedCrossRefGoogle Scholar
  89. 89.
    Kontny E, Prochorec-Sobieszek M. Articular adipose tissue resident macrophages in rheumatoid arthritis patients: potential contribution to local abnormalities. Rheumatology (Oxford). 2013;52:2158–67.CrossRefGoogle Scholar
  90. 90.
    Brooks-Wilson A, Marcil M, Clee SM, Zhang LH, Roomp K, van Dam M, et al. Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency. Nat Genet. 1999;22:336–45.PubMedCrossRefGoogle Scholar
  91. 91.
    McNeish J, Aiello RJ, Guyot D, Turi T, Gabel C, Aldinger C, et al. High density lipoprotein deficiency and foam cell accumulation in mice with targeted disruption of ATP-binding cassette transporter-1. Proc Natl Acad Sci U S A. 2000;97:4245–50.PubMedCentralPubMedCrossRefGoogle Scholar
  92. 92.
    Chung S, Sawyer JK, Gebre AK, Maeda N, Parks JS. Adipose tissue ATP binding cassette transporter A1 contributes to high-density lipoprotein biogenesis in vivo. Circulation. 2011;124:1663–72.PubMedCentralPubMedCrossRefGoogle Scholar
  93. 93.
    Lu B, Moser AH, Shigenaga JK, Feingold KR, Grunfeld C. Type II nuclear hormone receptors, coactivator, and target gene repression in adipose tissue in the acute-phase response. J Lipid Res. 2006;47:2179–90.PubMedCrossRefGoogle Scholar
  94. 94.
    Peterson SJ, Drummond G, Kim DH, Li M, Kruger AL, Ikehara S, et al. L-4F treatment reduces adiposity, increases adiponectin levels, and improves insulin sensitivity in obese mice. J Lipid Res. 2008;49:1658–69.PubMedCentralPubMedCrossRefGoogle Scholar
  95. 95.
    Keene D, Price C, Shun-Shin MJ, Francis DP. Effect on cardiovascular risk of high density lipoprotein targeted drug treatments niacin, fibrates, and CETP inhibitors: meta-analysis of randomised controlled trials including 117,411 patients. BMJ. 2014;349:g4379.PubMedCentralPubMedCrossRefGoogle Scholar

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© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Division of Rheumatology, College of Physicians and SurgeonsColumbia UniversityNew YorkUSA

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