Adipokines, diabetes and atherosclerosis: An inflammatory association

Frontiers in Physiology

Volumn 6, Issue NOV, 2015, Pages

  Freitas Lima, Leandro C ^a   Braga, Valdir de Andrade ^b   do Socorro de França Silva, Maria ^b   Cruz, Josiane de Campos ^b   Sousa Santos, Sérgio H ^a,c   de Oliveira Monteiro, Matheus M ^b   Balarini, Camille de Moura ^b  

^a FEDERAL UNIVERSITY OF MINAS GERAIS   (Brazil)

^b FEDERAL UNIVERSITY OF PARAÍBA   (Brazil)

^c STATE UNIVERSITY OF MONTES CLAROS   (Brazil)

Author keywords

Adipokines; Adiponectin; Atherosclerosis; Diabetes; IL 6; Leptin; MCP 1; TNFa

Indexed keywords

ADIPOCYTOKINE; ADIPONECTIN RECEPTOR; GLUCOSE; INSULIN; INTERLEUKIN 6; LEPTIN; MONOCYTE CHEMOTACTIC PROTEIN 1; PROTEIN KINASE; TUMOR NECROSIS FACTOR;

ADIPOSE TISSUE; ANTIINFLAMMATORY ACTIVITY; ATHEROSCLEROSIS; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CAUSE OF DEATH; CHRONIC DISEASE; DIABETIC PATIENT; DISEASE ASSOCIATION; GLUCOSE TOLERANCE; HUMAN; INFLAMMATION; INSULIN DEPENDENT DIABETES MELLITUS; INSULIN RESISTANCE; INSULIN SENSITIVITY; METABOLIC SYNDROME X; NON INSULIN DEPENDENT DIABETES MELLITUS; PATHOGENESIS; PATHOPHYSIOLOGY; REVIEW;

EID: 84949563295     PISSN: None     EISSN: 1664042X     Source Type: Journal    
DOI: 10.3389/fphys.2015.00304     Document Type: Review

References (164)

1. Adya, R., Tan, B. K., and Randeva, H. S. (2015). Differential effects of leptin and adiponectin in endothelial angiogenesis. J. Diabetes Res. 2015, 1-12. doi: 10.1155/2015/648239.
2. Ahima, R. S., and Flier, J. S. (2000). Leptin. Annu. Rev. Physiol. 62, 413-437. doi: 10.1146/annurev.physiol.62.1.413.
3. American Diabetes Association (2014). Standards of medical care in diabetes-2014. Diab. Care. 37. doi: 10.2337/dc14-S014.
4. Amitani, M., Asakawa, A., Amitani, H., and Inui, A. (2013). The role of leptin in the control of insulin-glucose axis. Front. Neurosci. 7:51. doi: 10.3389/fnins.2013.00051.
5. Arita, Y., Kihara, S., Ouchi, N., Takahashi, M., Maeda, K., Miyagawa, J., et al. (1999). Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem. Biophys. Res. Commun. 257, 79-83. doi: 10.1006/bbrc.1999.0255.
6. Arkan, M. C., Hevener, A. L., Greten, F. R., Maeda, S., Li, Z. W., Long, J. M., et al. (2005). IKK-beta links inflammation to obesity-induced insulin resistance. Nat. Med. 11, 191-198. doi: 10.1038/nm1185.
7. Awazawa, M., Ueki, K., Inabe, K., Yamauchi, T., Kubota, N., Kaneko, K., et al. (2011). Adiponectin enhances insulin sensitivity by increasing hepatic IRS-2 expression via a macrophage-derived IL-6-dependent pathway. Cell Metab. 13, 401-412. doi: 10.1016/j.cmet.2011.02.010.
8. Bahceci, M., Gokalp, D., Bahceci, S., Tuzcu, A., Atmaca, S., and Arikan, S. (2007). The correlation between adiposity and adiponectin, tumor necrosis factor alpha, interleukin-6 and high sensitivity C-reactive protein levels. Is adipocyte size associated with inflammation in adults? J. Endocrinol. Invest. 30. doi: 10.1007/BF03347427.
9. Balarini, C. M., Leal, M. A., Gomes, I. B. S., Pereira, T. M. C., Gava, A. L., Meyrelles, S. S., et al. (2013). Sildenafil restores endothelial function in the apolipoprotein E knockout mouse. J. Transl. Med. 11:3. doi: 10.1186/1479-5876-11-3.
10. Bays, H. E. (2009). "Sick Fat," metabolic disease, and atherosclerosis. Am. J. Med. 122, S26-S37. doi: 10.1016/j.amjmed.2008.10.015.
11. Beltowski, J. (2006). Leptin and atherosclerosis. Atherosclerosis 189, 47-60. doi: 10.1016/j.atherosclerosis.2006.03.003.
12. Berg, A. H., Combs, T. P., Du, X., Brownlee, M., and Scherer, P. E. (2001). The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat. Med. 7, 947-953. doi: 10.1038/90992.
13. Blüher, M. (2009). Adipose tissue dysfunction in obesity. Exp. Clin. Endocrinol. Diabetes. 117, 241-250. doi: 10.1055/s-0029-1192044.
14. Blüher, M. (2014). Adipokines-removing road blocks to obesity and diabetes therapy. Mol Metab. 3, 230-240. doi: 10.1016/j.molmet.2014.01.005.
15. Braga, V. A., Medeiros, I. A., Ribeiro, T. P., França-Silva, M. S., Botelho-Ono, M. S., and Guimarães, D. D. (2011). Angiotensin-II-induced reactive oxygen species along the SFO-PVN-RVLM pathway: implications in neurogenic hypertension. Brazilian J. Med. Biol. Res. 44, 871-876. doi: 10.1590/S0100-879X2011007500088.
16. Brånén, L., Hovgaard, L., Nitulescu, M., Bengtsson, E., Nilsson, J., and Jovinge, S. (2004). Inhibition of tumor necrosis factor-alpha reduces atherosclerosis in apolipoprotein E knockout mice. Arterioscler. Thromb. Vasc. Biol. 24, 2137-2142. doi: 10.1161/01.ATV.0000143933.20616.1b.
17. Cardellini, M., Menghini, R., Luzi, A., Davato, F., Cardolini, I., D'Alfonso, R., et al. (2011). Decreased IRS2 and TIMP3 expression in monocytes from offspring of type 2 diabetic patients is correlated with insulin resistance and increased intima-media thickness. Diabetes. 60, 3265-3270. doi: 10.2337/db11-0162.
18. Cardellini, M., Menghini, R., Martelli, E., Casagrande, V., Marino, A., Rizza, S., et al. (2009). TIMP3 is reduced in atherosclerotic plaques from subjects with type 2 diabetes and increased by SirT1. Diabetes. 58, 2396-2401. doi: 10.2337/db09-0280.
19. Caselli, C., D'Amico, A., Cabiati, M., Prescimone, T., Del Ry, S., and Gianness, D. (2014). Back to the heart: the protective role of adiponectin. Pharmacol. Res. 82, 9-20. doi: 10.1016/j.phrs.2014.03.003.
20. Cassis, L. A., English, V. L., Bharadwaj, K., and Boustany, C. M. (2004). Differential effects of local versus systemic angiotensin II in the regulation of leptin release from adipocytes. Endocrinology 145, 169-174. doi: 10.1210/en.2003-0767.
21. Cesari, M., Penninx, B. W., Newman, A. B., Kritchevsky, S. B., Nicklas, B. J., Sutton-Tyrrell, K., et al. (2003). Inflammatory markers and onset of cardiovascular events: results from the Health ABC study. Circulation 108, 2317-2322. doi: 10.1161/01.CIR.0000097109.90783.FC.
22. Chaldakov, G. N., Fiore, M., Ghenev, P. I., Beltowski, J., Rancic, G., Tunçel, N., et al. (2014). Triactome: neuro-immune-adipose interactions. Implication in vascular biology. Front Immunol. 5:130. doi: 10.3389/fimmu.2014.00130.
23. Charo, I. F., and Taubman, M. B. (2004). Chemokines in the pathogenesis of vascular disease. Circ. Res. 95, 858-866. doi: 10.1161/01.RES.0000146672.10582.17.
24. Chavey, C., Mari, B., Monthouel, M. N., Bonnafous, S., Anglard, P., Van Obberghen, E., et al. (2003). Matrix metalloproteinases are differentially expressed in adipose tissue during obesity and modulate adipocyte differentiation. J. Biol. Chem. 278, 11888-11896. doi: 10.1074/jbc. M209196200.
25. Chen, M. B., McAinch, A. J., Macaulay, S. L., Castelli, L. A., O'brien, P. E, Dixon, J. B., et al. (2005). Impaired activation of AMP-kinase and fatty acid oxidation by globular adiponectin in cultured human skeletal muscle of obese type 2 diabetics. J. Clin. Endocrinol. Metab. 90. doi: 10.1210/jc.2004-1980.
26. Chen, Q., Fisher, D. T., Clancy, K. A., Gauguet, J.-M. M., Wang, W.-C., Unger, E., et al. (2006). Fever-range thermal stress promotes lymphocyte trafficking across high endothelial venules via an interleukin 6 trans-signaling mechanism. Nat. Immunol. 7, 1299-1308. doi: 10.1038/ni1406.
27. Chomarat, P., Banchereau, J., Davoust, J., and Palucka, A. K. (2000). IL-6 switches the differentiation of monocytes from dendritic cells to macrophages. Nat. Immunol. 1, 510-514. doi: 10.1038/82763.
28. Cildir, G., Akincilar, S. C., and Tergaonkar, V. (2013). Chronic adipose tissue inflammation: all immune cells on the stage. Trends Mol. Med. 19, 487-500. doi: 10.1016/j.molmed.2013.05.001.
29. Cushing, S. D., Berlinert, J. A., Valentet, A. J., Territo, M. C., Navab, M., Parhamit, F., et al. (1990). Minimally modified low density lipoprotein induces monocyte chemotactic protein 1 in human endothelial cells and smooth muscle cells. Proc. Natl. Acad. Sci. U.S.A. 87, 5134-5138. doi: 10.1073/pnas.87.13.5134.
30. Dong, F., Zhang, X., and Ren, J. (2006). Leptin regulates cardiomyocyte contractile function through endothelin-1 receptor-NADPH oxidase pathway. Hypertension 47, 222-229. doi: 10.1161/01.HYP.0000198555.51645.f1.
31. Du, G., Song, Y., Zhang, T., Ma, L., Bian, N., Chen, X., et al. (2014). Simvastatin attenuates TNFa-induced apoptosis in endothelial progenitor cells via the upregulation of SIRT1. Int. J. Mol. Med. 34, 177-182. doi: 10.3892/ijmm.2014.1740.
32. Dussault, S., Maingrette, F., Ménard, C., Michaud, S.-E., Haddad, P., Groleau, J., et al. (2009). Sildenafil increases endothelial progenitor cell function and improves ischemia-induced neovascularization in hypercholesterolemic apolipoprotein E-deficient mice. Hypertension 54, 1043-1049. doi: 10.1161/HYPERTENSIONAHA.109.139451.
33. Ekstrand, M., Gustafsson Trajkovska, M., Perman-Sundelin, J., Fogelstrand, P., Adiels, M., Johansson, M., et al. (2015). Imaging of intracellular and extracellular ROS levels in atherosclerotic mouse aortas ex vivo: effects of lipid lowering by diet or atorvastatin. PLoS ONE 10:e0130898. doi: 10.1371/journal.pone.0130898.
34. Elmquist, J. K., Elias, C. F., and Saper, C. B. (1999). From lesions to leptin: hypothalamic control of food intake and body weight. Neuron 22, 221-232. doi: 10.1016/S0896-6273(00)81084-3.
35. Esposito, K., Pontillo, A., Di Palo, C., Giugliano, G., Masella, M., Marfella, R., et al. (2003). Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA 289, 1799-1804. doi: 10.1001/jama.289.14.1799.
36. Ferreira-Hermosillo, A., Molina-Ayala, M., Ramírez-Rentería, C., Vargas, G., Gonzalez, B., Isibasi, A., et al. (2015). Inflammatory cytokine profile associated with metabolic syndrome in adult patients with type 1 diabetes. J. Diabetes Res. 2015:972073. doi: 10.1155/2015/972073.
37. Fisman, E. Z., and Tenenbaum, A. (2014). Adiponectin: a manifold therapeutic target for metabolic syndrome, diabetes, and coronary disease? Cardiovasc. Diabetol. 13:103. doi: 10.1186/1475-2840-13-103.
38. Franckhauser, S., Elias, I., Rotter Sopasakis, V., Ferré, T., Nagaev, I., Andersson, C. X., et al. (2008). Overexpression of Il6 leads to hyperinsulinaemia, liver inflammation and reduced body weight in mice. Diabetologia 51, 1306-1316. doi: 10.1007/s00125-008-0998-8.
39. Fruebis, J., Tsao, T. S., Javorschi, S., Ebbets-Reed, D., Erickson, M. R., Yen, F. T., et al. (2001). Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc. Natl. Acad. Sci. U.S.A. 98, 2005-2010. doi: 10.1073/pnas.98.4.2005.
40. Galic, S., Oakhill, J. S., and Steinberg, G. R. (2010). Adipose tissue as an endocrine organ. Mol. Cell. Endocrinol. 316, 129-139. doi: 10.1016/j.mce.2009.08.018.
41. Gonzalez-Quesada, C., and Frangogiannis, N. G. (2009). Monocyte chemoattractant protein-1/CCL2 as a biomarker in acute coronary syndromes. Curr. Atheroscler. Rep. 11, 131-138. doi: 10.1007/s11883-009-0021-y.
42. Hahn, B. H., Grossman, J., Chen, W., and McMahon, M. (2007). The pathogenesis of atherosclerosis in autoimmune rheumatic diseases: roles of inflammation and dyslipidemia. J. Autoimmun 28, 2-3. doi: 10.1016/j.jaut.2007.02.004.
43. Hansson, G. K., Libby, P., Schönbeck, U., and Yan, Z.-Q. (2002). Innate and adaptive immunity in the pathogenesis of atherosclerosis. Circ. Res. 91, 281-291. doi: 10.1161/01.RES.0000029784.15893.10.
44. Hao, G., Li, W., Guo, R., Yang, J.-G., Wang, Y., Tian, Y., et al. (2013). Serum total adiponectin level and the risk of cardiovascular disease in general population: a meta-analysis of 17 prospective studies. Atherosclerosis 228, 29-35. doi: 10.1016/j.atherosclerosis.2013.02.018.
45. Hashizume, M., and Mihara, M. (2012). Blockade of IL-6 and TNF-a inhibited oxLDL-induced production of MCP-1 via scavenger receptor induction. Eur. J. Pharmacol. 689, 249-254. doi: 10.1016/j.ejphar.2012.05.035.
46. Hassan, W., Ding, L., Gao, R. Y., Liu, J., and Shang, J. (2014). Interleukin-6 signal transduction and its role in hepatic lipid metabolic disorders. Cytokine 66, 133-142. doi: 10.1016/j.cyto.2013.12.017.
47. Havel, P. J. (2002). Control of energy homeostasis and insulin action by adipocyte hormones: leptin, acylation stimulating protein, and adiponectin. Curr. Opin. Lipidol. 13, 51-59. doi: 10.1097/00041433-200202000-00008.
48. Herbrig, K., Haensel, S., Oelschlaegel, U., Pistrosch, F., Foerster, S., and Passauer, J. (2006). Endothelial dysfunction in patients with rheumatoid arthritis is associated with a reduced number and impaired function of endothelial progenitor cells. Ann. Rheum. Dis. 65, 157-163. doi: 10.1136/ard.2005.035378.
49. Hirosumi, J., Tuncman, G., Chang, L., Görgün, C. Z., Uysal, K. T., Maeda, K., et al. (2002). A central role for JNK in obesity and insulin resistance. Nature 420, 333-336. doi: 10.1038/nature01137.
50. Holmes, R. M., Yi, Z., De Filippis, E., Berria, R., Shahani, S., Sathyanarayana, P., et al. (2011). Increased abundance of the adaptor protein containing pleckstrin homology domain, phosphotyrosine binding domain and leucine zipper motif (APPL1) in patients with obesity and type 2 diabetes: evidence for altered adiponectin signalling. Diabetologia. 54, 2122-2131. doi: 10.1007/s00125-011-2173-x.
51. Hotamisligil, G. S., Shargill, N. S., and Spiegelman, B. M. (1993). Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259, 87-91. doi: 10.1126/science.7678183.
52. Huang, D., Yang, C., Wang, Y., Liao, Y., and Huang, K. (2009). PARP-1 suppresses adiponectin expression through poly[ADP-ribosyl]ation of PPAR gamma in cardiac fibroblasts. Cardiovasc. Res. 81, 98-107. doi: 10.1093/cvr/cvn264.
53. Huang, P. H., Chen, J. S., Tsai, H. Y., Chen, Y. H., Lin, F. Y., Leu, H. B., et al. (2011). Globular adiponectin improves high glucose-suppressed endothelial progenitor cell function through endothelial nitric oxide synthase dependent mechanisms. J. Mol. Cell. Cardiol. 51, 109-119. doi: 10.1016/j.yjmcc.2011.03.008.
54. Husain, K. (2015). Inflammation, oxidative stress and renin angiotensin system in atherosclerosis. World J. Biol. Chem. 6:209. doi: 10.4331/wjbc.v6.i3.209.
55. International Diabetes Federation (2013). IDF Diabetes Atlas. 6th Edn. Brussels: International Diabetes Federation.
56. Issan, Y., Hochhauser, E., Kornowski, R., Leshem-Lev, D., Lev, E., Sharoni, R., et al. (2012). Endothelial progenitor cell function inversely correlates with long-term glucose control in diabetic patients: association with the attenuation of the heme oxygenase-adiponectin axis. Can. J. Cardiol. 28, 728-736. doi: 10.1016/j.cjca.2012.01.013.
57. Jäger, S., Handschin, C., St-Pierre, J., and Spiegelman, B. M. (2007). AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha. Proc. Natl. Acad. Sci. U.S.A. 104, 12017-12022. doi: 10.1073/pnas.0705070104.
58. Jang, C., Inder, W. J., Obeyesekere, V. R., and Alford, F. P. (2008). Adiponectin, skeletal muscle adiponectin receptor expression and insulin resistance following dexamethasone. Clin. Endocrinol. (Oxf). 69, 745-750. doi: 10.1111/j.1365-2265.2008.03242.x.
59. Jung, U. J., and Choi, M. S. (2014). Obesity and its metabolic complications: the role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int. J. Mol. Sci. 15, 6184-6223. doi: 10.3390/ijms15046184.
60. Kadowaki, T., Yamauchi, T., Kubota, N., Hara, K., Ueki, K., and Tobe, K. (2006). Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J. Clin. Invest. 116, 1784-1792. doi: 10.1172/JCI29126.
61. Kanda, H., Tateya, S., Tamori, Y., Kotani, K., Hiasa, K., Kitazawa, R., et al. (2006). MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J. Clin. Invest. 116, 1494-1505. doi: 10.1172/JCI26498.
62. Kim, J. A., Nuñez, M., Briggs, D. B., Laskowski, B. L., Chhun, J. J., Eleid, J. K., et al. (2012). Extracellular conversion of adiponectin hexamers into trimers. Biosci. Rep. 32, 641-652. doi: 10.1042/BSR20120067.
63. Kishida, K., Funahashi, T., and Shimomura, I. (2014). Adiponectin as a routine clinical biomarker. Best Pract. Res. Clin. Endocrinol. Metab. 28, 119-130. doi: 10.1016/j.beem.2013.08.006.
64. Kobayasi, R., Akamine, E. H., Davel, A. P., Rodrigues, M. A. M., Carvalho, C. R. O., and Rossoni, L. V. (2010). Oxidative stress and inflammatory mediators contribute to endothelial dysfunction in high-fat diet-induced obesity in mice. J. Hypertens 28, 2111-2119. doi: 10.1097/HJH.0b013e32833ca68c.
65. Koh, K. K., Park, S. M., and Quon, M. J. (2008). Leptin and cardiovascular disease: response to therapeutic interventions. Circulation 117, 3238-3249. doi: 10.1161/CIRCULATIONAHA.107.741645.
66. Koh, K. K., Park, S. M., and Quon, M. J. (2012). Leptin and cardiovascular diseases: response to therapeutic interventions. Circulation 117, 3238-3249. doi: 10.1161/CIRCULATIONAHA.107.741645.
67. Krysiak, R., Z˙muda, W., and Okopień, B. (2014). The effect of short-term simvastatin treatment on plasma adipokine levels in patients with isolated hypercholesterolemia: a preliminary report. Pharmacol. Rep. 66, 880-884. doi: 10.1016/j.pharep.2014.05.012.
68. Kumada, M., Kihara, S., Ouchi, N., Kobayashi, H., Okamoto, Y., Ohashi, K., et al. (2004). Adiponectin specifically increased tissue inhibitor of metalloproteinase-1 through interleukin-10 expression in human macrophages. Circulation 109, 2046-2049. doi: 10.1161/01.CIR.0000127953.98131.ED.
69. Lee, B. C., and Lee, J. (2014). Cellular and molecular players in adipose tissue inflammation in the development of obesity-induced insulin resistance. Biochim. Biophys. Acta. 1842, 446-462. doi: 10.1016/j.bbadis.2013.05.017.
70. Lehr, S., Hartwig, S., and Sell, H. (2012). Adipokines: a treasure trove for the discovery of biomarkers for metabolic disorders. Proteomics Clin. Appl. 6, 1-2. doi: 10.1002/prca.201100052.
71. Li, L., Mamputu, J.-C., Wiernsperger, N., and Renier, G. (2005). Signaling pathways involved in human vascular smooth muscle cell proliferation and matrix metalloproteinase-2 expression induced by leptin: inhibitory effect of metformin. Diabetes. 54, 2227-2234. doi: 10.2337/diabetes.54.7.2227.
72. Li, Z., Yang, S., Lin, H., Huang, J., Watkins, P. A., Moser, A. B., et al. (2003). Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease. Hepatology 37, 343-350. doi: 10.1053/jhep.2003.50048.
73. Liang, H., Yin, B., Zhang, H., Zhang, S., Zeng, Q., Wang, J., et al. (2008). Blockade of tumor necrosis factor (TNF) receptor type 1-mediated TNF-alpha signaling protected Wistar rats from diet-induced obesity and insulin resistance. Endocrinology 149, 2943-2951. doi: 10.1210/en.2007-0978.
74. Libby, P. (2002). Inflammation in atherosclerosis. Nature 420, 868-874. doi: 10.1038/nature01323.
75. Libby, P., Okamoto, Y., Rocha, V. Z., and Folco, E. (2010). Inflammation in atherosclerosis: transition from theory to practice. Circ. J. 74, 213-220. doi: 10.1253/circj.cj-09-0706.
76. Lim, S., Quon, M. J., and Koh, K. K. (2014). Modulation of adiponectin as a potential therapeutic strategy. Atherosclerosis. 233, 721-728. doi: 10.1016/j.atherosclerosis.2014.01.051.
77. Lin, J., Kakkar, V., and Lu, X. (2014). Impact of MCP-1 in Atherosclerosis. Curr. Pharm. Des. 20, 4580-4588. doi: 10.2174/1381612820666140522115801.
78. Lindgren, A., Levin, M., Blomqvist, R. S., Wikström, J., Ahnmark, A., Mogensen, C., et al. (2013). Adiponectin receptor 2 deficiency results in reduced atherosclerosis in the brachiocephalic artery in apolipoprotein e deficient mice. PLoS ONE 8:11. doi: 10.1371/journal.pone.0080330.
79. López-Soriano, J., López-Soriano, F. J., Bagby, G. J., Williamson, D. H., and Argilés, J. M. (1997). Anti-TNF treatment does not reverse the abnormalities in lipid metabolism of the obese Zucker rat. Am. J. Physiol. 272, E656-E660.
80. Lumeng, C. N., and Saltiel, A. R. (2011). Inflammatory links between obesity and metabolic disease. J. Clin. Invest. 121, 2111-2117. doi: 10.1172/JCI57132.
81. Lusis, A. J. (2000). Atherosclerosis. Nature. 407, 233-241. doi: 10.1038/35025203.
82. Marcos-Ramiro, B., García-Weber, D., and Millán, J. (2014). TNF-induced endothelial barrier disruption: beyond actin and Rho. Thromb. Haemost. 112, 1088-1102. doi: 10.1160/TH14-04-0299.
83. Mark, A. L., Correia, M. L. G., Rahmouni, K., and Haynes, W. G. (2002). Selective leptin resistance: a new concept in leptin physiology with cardiovascular implications. J. Hypertens. 20, 1245-1250. doi: 10.1097/00004872-200207000-00001.
84. Marroquí, L., Gonzalez, A., Ñeco, P., Caballero-Garrido, E., Vieira, E., Ripoll, C., et al. (2012). Role of leptin in the pancreatic ß-cell: effects and signaling pathways. J. Mol. Endocrinol. 49, R9-R17. doi: 10.1530/JME-12-0025.
85. Matthews, V., Schuster, B., Schütze, S., Bussmeyer, I., Ludwig, A., Hundhausen, C., et al. (2003). Cellular cholesterol depletion triggers shedding of the human interleukin-6 receptor by ADAM10 and ADAM17 (TACE). J. Biol. Chem. 278, 38829-38839. doi: 10.1074/jbc. M210584200.
86. Mattu, H. S., and Randeva, H. S. (2013). Role of adipokines in cardiovascular disease. J. Endocrinol. 216, T17-T36. doi: 10.1530/JOE-12-0232.
87. Mazurek, T., Zhang, L., Zalewski, A., Mannion, J. D., Diehl, J. T., Arafat, H., et al. (2003). Human epicardial adipose tissue is a source of inflammatory mediators. Circulation 108, 2460-2466. doi: 10.1161/01.CIR.0000099542.57313.C5.
88. Menghini, R., Fiorentino, L., Casagrande, V., Lauro, R., and Federici, M. (2013). The role of ADAM-17 in metabolic inflammation. Atherosclerosis 228, 12-17. doi: 10.1016/j.atherosclerosis.2013.01.024.
89. Nakamura, K., Fuster, J. J., and Walsh, K. (2014). Adipokines: a link between obesity and cardiovascular disease. J. Cardiol. 63, 250-259. doi: 10.1016/j.jjcc.2013.11.006.
90. Namiki, M., Kawashima, S., Yamashita, T., Ozaki, M., Hirase, T., Ishida, T., et al. (2002). Local overexpression of monocyte chemoattractant protein-1 at vessel wall induces infiltration of macrophages and formation of atherosclerotic lesion: synergism with hypercholesterolemia. Arterioscler. Thromb. Vasc. Biol. 22, 115-120. doi: 10.1161/hq0102.102278.
91. Nishimoto, N., Kanakura, Y., Aozasa, K., Johkoh, T., Nakamura, M., Nakano, S., et al. (2005). Humanized anti-interleukin-6 receptor antibody treatment of multicentric Castleman disease. Blood 106, 2627-2632. doi: 10.1182/blood-2004-12-4602.
92. Ntaios, G., Gatselis, N. K., Makaritsis, K., and Dalekos, G. N. (2013). Adipokines as mediators of endothelial function and atherosclerosis. Atherosclerosis 227, 216-221. doi: 10.1016/j.atherosclerosis.2012.12.029.
93. Ohman, M. K., Shen, Y., Obimba, C. I., Wright, A. P., Warnock, M., Lawrence, D. A., et al. (2008). Visceral adipose tissue inflammation accelerates atherosclerosis in apolipoprotein E-deficient mice. Circulation 117, 798-805. doi: 10.1161/CIRCULATIONAHA.107.717595.
94. Ohta, H., Wada, H., Niwa, T., Kirii, H., Iwamoto, N., Fujii, H., et al. (2005). Disruption of tumor necrosis factor-alpha gene diminishes the development of atherosclerosis in ApoE-deficient mice. Atherosclerosis 180, 11-17. doi: 10.1016/j.atherosclerosis.2004.11.016.
95. Okada-Iwabu, M., Yamauchi, T., Iwabu, M., Honma, T., Hamagami, K., Matsuda, K., et al. (2013). A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity. Nature 503, 493-499. doi: 10.1038/nature12656.
96. Ouchi, N., Kihara, S., Arita, Y., Maeda, K., Kuriyama, H., Okamoto, Y., et al. (1999). Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation 100, 2473-2476. doi: 10.1161/01.CIR.100.25.2473.
97. Ouchi, N., Kihara, S., Arita, Y., Nishida, M., Matsuyama, A., Okamoto, Y., et al. (2001). Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation 103, 1057-1063. doi: 10.1161/01.CIR.103.8.1057.
98. Ouchi, N., Kihara, S., Arita, Y., Okamoto, Y., Maeda, K., Kuriyama, H., et al. (2000). Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway. Circulation 102, 1296-1301. doi: 10.1161/01.CIR.102.11.1296.
99. Palomer, X., Salvadó, L., Barroso, E., and Vázquez-Carrera, M. (2013). An overview of the crosstalk between inflammatory processes and metabolic dysregulation during diabetic cardiomyopathy. Int. J. Cardiol. 168, 3160-3172. doi: 10.1016/j.ijcard.2013.07.150.
100. Panee, J. (2012). Monocyte Chemoattractant Protein 1 (MCP-1) in Obesity and Diabetes. Cytokine 60, 1-12. doi: 10.1016/j.cyto.2012.06.018.
101. Peschon, J. J., Slack, J. L., Reddy, P., Stocking, K. L., Sunnarborg, S. W., Lee, D. C., et al. (1998). An essential role for ectodomain shedding in mammalian development. Science 282, 1281-1284. doi: 10.1126/science.282.5392.1281.
102. Piya, M. K., McTernan, P. G., and Kumar, S. (2013). Adipokine inflammation and insulin resistance: the role of glucose, lipids and endotoxin. J. Endocrinol. 216, T1-T15. doi: 10.1530/JOE-12-0498.
103. Protogerou, A. D., Zampeli, E., Fragiadaki, K., Stamatelopoulos, K., Papamichael, C., and Sfikakis, P. P. (2011). A pilot study of endothelial dysfunction and aortic stiffness after interleukin-6 receptor inhibition in rheumatoid arthritis. Atherosclerosis 219, 734-736. doi: 10.1016/j.atherosclerosis.2011.09.015.
104. Rezaie-Majd, A., Maca, T., Bucek, R. A., Valent, P., Müller, M. R., Husslein, P., et al. (2002). Simvastatin reduces expression of cytokines interleukin-6, interleukin-8, and monocyte chemoattractant protein-1 in circulating monocytes from hypercholesterolemic patients. Arterioscler. Thromb. Vasc. Biol. 22, 1194-1199. doi: 10.1161/01.ATV.0000022694.16328.CC.
105. Ridker, P. M., and Lüscher, T. F. (2014). Anti-inflammatory therapies for cardiovascular disease. Eur. Heart J. 35, 1782-1791. doi: 10.1093/eurheartj/ehu203.
106. Rodriguez, A. L., Wojcik, B. M., Wrobleski, S. K., Myers, D. D. Jr. Wakefield, T. W., and Diaz, J. A. (2012). Statins, inflammation and deep vein thrombosis: a systematic review. J. Thromb. Thrombolysis 33, 371-382. doi: 10.1007/s11239-012-0687-9.
107. Ronti, T., Lupattelli, G., and Mannarino, E. (2006). The endocrine function of adipose tissue: an update. Clin. Endocrinol. (Oxf). 64, 355-365. doi: 10.1111/j.1365-2265.2006.02474.x.
108. Rose-John, S., Scheller, J., and Schaper, F. (2015). "Family reunion"-a structured view on the composition of the receptor complexes of interleukin-6-type and interleukin-12-type cytokines. Cytokine Growth Factor Rev. 26, 471-474. doi: 10.1016/j.cytogfr.2015.07.011.
109. Rosenfeld, M. E. (2013). Inflammation and atherosclerosis: direct versus indirect mechanisms. Curr. Opin. Pharmacol. 13, 154-160. doi: 10.1016/j.coph.2013.01.003.
110. Ross, R. (1999). Atherosclerosis-an inflammatory disease. N. Engl. J. Med. 340, 115-126. doi: 10.1016/s0002-8703(99)70266-8.
111. Rubanyi, G. M. (1993). The role of endothelium in cardiovascular homeostasis and diseases. J. Cardiovasc. Pharmacol. 22(Suppl. 4), S1-S14. doi: 10.1097/00005344-199322004-00002.
112. Sabio, G., and Davis, R. J. (2010). cJun NH2-terminal kinase 1 (JNK1): roles in metabolic regulation of insulin resistance. Trends Biochem. Sci. 35, 490-496. doi: 10.1016/j.tibs.2010.04.004.
113. Scheid, M. P., and Sweeney, G. (2014). The role of adiponectin signaling in metabolic syndrome and cancer. Rev. Endocr. Metab. Disord. 15, 157-167. doi: 10.1007/s11154-013-9265-5.
114. Scheller, J., Chalaris, A., Schmidt-Arras, D., and Rose-John, S. (2011). The pro-and anti-inflammatory properties of the cytokine interleukin-6. Biochim. Biophys. Acta Mol. Cell Res. 1813, 878-888. doi: 10.1016/j.bbamcr.2011.01.034.
115. Schroeter, M. R., Stein, S., Heida, N. M., Leifheit-Nestler, M., Cheng, I. F., Gogiraju, R., et al. (2012). Leptin promotes the mobilization of vascular progenitor cells and neovascularization by NOX2-mediated activation of MMP9. Cardiovasc. Res. 93, 170-180. doi: 10.1093/cvr/cvr275.
116. Schuett, H., Luchtefeld, M., Grothusen, C., Grote, K., and Schieffer, B. (2009). How much is too much? Interleukin-6 and its signalling in atherosclerosis. Thromb. Haemost. 102, 215-222. doi: 10.1160/th09-05-0297.
117. Scotece, M., Conde, J., Gómez, R., López, V., Pino, J., González, A., et al. (2012). Role of adipokines in atherosclerosis: interferences with cardiovascular complications in rheumatic diseases. Mediators Inflamm. 2012:125458. doi: 10.1155/2012/125458.
118. Segal, K. R., Landt, M., and Klein, S. (1996). Relationship between insulin sensitivity and plasma leptin concentration in lean and obese men. Diabetes 45, 988-991. doi: 10.2337/diab.45.7.988.
119. Seufert, J. (2004). Leptin effects on pancreatic beta-cell gene expression and function. Diabetes 53, S152-S158. doi: 10.2337/diabetes.53.2007.S152.
120. Sindhu, S., Thomas, R., Shihab, P., Sriraman, D., Behbehani, K., and Ahmad, R. (2015). Obesity is a positive modulator of IL-6R and IL-6 expression in the subcutaneous adipose tissue: significance for metabolic inflammation. PLoS ONE 10:e0133494. doi: 10.1371/journal.pone.0133494.
121. Singh, P., Peterson, T. E., Barber, K. R., Kuniyoshi, F. S., Jensen, A., Hoffmann, M., et al. (2010). Leptin upregulates the expression of plasminogen activator inhibitor-1 in human vascular endothelial cells. Biochem. Biophys. Res. Commun. 392, 47-52. doi: 10.1016/j.bbrc.2009.12.158.
122. Skurk, T., Alberti-Hube, C., Herder, C., and Hauner, H. (2007). Relationship between Adipocyte Size and Adipokine Expression and Secretion. J. Clin. Endocrinol. Metab. 92, 1023-1033. doi: 10.1210/jc.2006-1055.
123. Skyler, J. S., Bergenstal, R., Bonow, R. O., Buse, J., Deedwania, P., Gale, E. A. M., et al. (2009). Intensive glycemic control and the prevention of cardiovascular events: implications of the ACCORD, ADVANCE, and VA diabetes trials. a position statement of the american diabetes association and a scientific statement of the american college of cardiology foundation and the american heart association. Diabetes Care 32, 187-192. doi: 10.1016/j.jacc.2008.10.008.
124. Solinas, G., Vilcu, C., Neels, J. G., Bandyopadhyay, G. K., Luo, J. L., Naugler, W., et al. (2007). JNK1 in hematopoietically derived cells contributes to diet-induced inflammation and insulin resistance without affecting obesity. Cell Metab. 6, 386-397. doi: 10.1016/j.cmet.2007.09.011.
125. Speck, N., Brandsch, C., Schmidt, N., Yazdekhasti, N., Hirche, F., Lucius, R., et al. (2015). The Antiatherogenic Effect of Fish Oil in Male Mice Is Associated with a Diminished Release of Endothelial ADAM17 and ADAM10 Substrates. J. Nutr. 145, 1218-1226. doi: 10.3945/jn.115.211375.
126. Stephen, S. L., Freestone, K., Dunn, S., Twigg, M. W., Homer-Vanniasinkam, S., Walker, J. H., et al. (2010). scavenger receptors and their potential as therapeutic targets in the treatment of cardiovascular disease. Int. J. Hypertens. 2010:646929. doi: 10.4061/2010/646929.
127. Steyers, C. M., and Miller, F. J. (2014). Endothelial dysfunction in chronic inflammatory diseases. Int. J. Mol. Sci. 15, 11324-11349. doi: 10.3390/ijms150711324.
128. Swarbrick, M. M., and Havel, P. J. (2008). Physiological, pharmacological, and nutritional regulation of circulating adiponectin concentrations in humans. Metab. Syndr. Relat. Disord. 6, 87-102. doi: 10.1089/met.2007.0029.
129. Tabas, I., Williams, K. J., and Borén, J. (2007). Subendothelial lipoprotein retention as the initiating process in atherosclerosis: update and therapeutic implications. Circulation 116, 1832-1844. doi: 10.1161/CIRCULATIONAHA.106.676890.
130. Tabata, T., Mine, S., Kawahara, C., Okada, Y., and Tanaka, Y. (2003). Monocyte chemoattractant protein-1 induces scavenger receptor expression and monocyte differentiation into foam cells. Biochem. Biophys. Res. Commun. 305, 380-385. doi: 10.1016/S0006-291X(03)00771-X.
131. Tarantino, G., and Caputi, A. (2011). JNKs, insulin resistance and inflammation: a possible link between NAFLD and coronary artery disease. World J. Gastroenterol. 17, 3785-3794. doi: 10.3748/wjg.v17.i33.3785.
132. Tavora, F., Kutys, R., Li, L., Ripple, M., Fowler, D., and Burke, A. (2010). Adventitial lymphocytic inflammation in human coronary arteries with intimal atherosclerosis. Cardiovasc. Pathol. 19, e61-e68. doi: 10.1016/j.carpath.2009.02.001.
133. Thorp, A. A., and Schlaich, M. P. (2015). Relevance of sympathetic nervous system activation in obesity and metabolic syndrome. J. Diabetes Res. 2015:341583. doi: 10.1155/2015/341583.
134. Tikellis, C., Pickering, R. J., Tsorotes, D., Huet, O., Chin-Dusting, J., Cooper, M. E., et al. (2012). Activation of the renin-angiotensin system mediates the effects of dietary salt intake on atherogenesis in the apolipoprotein E knockout mouse. Hypertension 60, 98-105. doi: 10.1161/HYPERTENSIONAHA.112.191767.
135. Timar, R., Timar, B., Degeratu, D., Serafinceanu, C., and Oancea, C. (2014). Metabolic syndrome, adiponectin and proinflammatory status in patients with type 1 diabetes mellitus. J. Int. Med. Res. 42, 1131-1138. doi: 10.1177/0300060514541829.
136. Tsubakio-Yamamoto, K., Matsuura, F., Koseki, M., Oku, H., Sandoval, J. C., Inagaki, M., et al. (2008). Adiponectin prevents atherosclerosis by increasing cholesterol efflux from macrophages. Biochem. Biophys. Res. Commun. 375, 390-394. doi: 10.1016/j.bbrc.2008.08.009.
137. Uchida, Y., Takeshita, K., Yamamoto, K., Kikuchi, R., Nakayama, T., Nomura, M., et al. (2012). Stress augments insulin resistance and prothrombotic state: role of visceral adipose-derived monocyte chemoattractant protein-1. Diabetes 61, 1552-1561. doi: 10.2337/db11-0828.
138. Umeda, M., Kanda, T., and Murakami, M. (2003). Effects of angiotensin II receptor antagonists on insulin resistance syndrome and leptin in sucrose-fed spontaneously hypertensive rats. Hypertens. Res. 26, 485-492. doi: 10.1291/hypres.26.485.
139. Van de Voorde, J., Pauwels, B., Boydens, C., and Decaluwé, K. (2013). Adipocytokines in relation to cardiovascular disease. Metab. Clin. Exp. 62, 1513-1521. doi: 10.1016/j.metabol.2013.06.004.
140. Virchow, R. (1858). Cellular Pathology as Based Upon Physiological and Pathological Histology. Birmingham, AL: Classics of Medicine Library. 361.
141. Virchow, R. (1989). Cellular pathology. As based upon physiological and pathological histology. Lecture XVI-Atheromatous affection of arteries. 1858. Nutr Rev. 47, 23-25. doi: 10.1111/j.1753-4887.1989.tb02747.x.
142. Waki, H., Yamauchi, T., Kamon, J., Kita, S., Ito, Y., Hada, Y., et al. (2005). Generation of globular fragment of adiponectin by leukocyte elastase secreted by monocytic cell line THP-1. Endocrinology 146, 790-796. doi: 10.1210/en.2004-1096.
143. Wang, P., Ba, Z. F., and Chaudry, I. H. (1994). Administration of tumor necrosis factor-alpha in vivo depresses endothelium-dependent relaxation. Am. J. Physiol. 266, 2535-2541.
144. Wascher, T. C., Lindeman, J. H. N., Sourij, H., Kooistra, T., Pacini, G., and Roden, M. (2011). Chronic TNFa neutralization does not improve insulin resistance or endothelial function in "healthy" men with metabolic syndrome. Mol. Med. Camb. Mass. 17, 3-4. doi: 10.2119/molmed.2010.00221.
145. Watanabe, N., and Ikeda, U. (2004). Matrix metalloproteinases and atherosclerosis. Curr. Atheroscler. Rep. 65, 112-120. doi: 10.1007/s11883-004-0099-1.
146. Weisberg, S. P., Hunter, D., Huber, R., Lemieux, J., Slaymaker, S., Vaddi, K., et al. (2006). CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J. Clin. Invest. 116, 115-124. doi: 10.1172/JCI24335.
147. Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L., and Ferrante, A. W. (2003). Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest. 112, 1796-1808. doi: 10.1172/JCI200319246.
148. Wellen, K. E., and Hotamisligil, G. S. (2005). Inflammation, stress, and diabetes. J. Clin. Invest. 115, 1111-1119. doi: 10.1172/JCI200525102.
149. Werle, M., Schmal, U., Hanna, K., and Kreuzer, J. (2002). MCP-1 induces activation of MAP-kinases ERK, JNK and p38 MAPK in human endothelial cells. Cardiovasc. Res. 56, 284-292. doi: 10.1016/S0008-6363(02)00600-4.
150. Weyer, C., Funahashi, T., Tanaka, S., Hotta, K., Matsuzawa, Y., Pratley, R. E., et al. (2001). Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J. Clin. Endocrinol. Metab. 86, 1930-1935. doi: 10.1210/jcem.86.5.7463.
151. Xia, H., Sriramula, S., Chhabra, K. H., and Lazartigues, E. (2013). Brain angiotensin-converting enzyme type 2 shedding contributes to the development of neurogenic hypertension. Circ. Res. 113, 1087-1096. doi: 10.1161/CIRCRESAHA.113.301811.
152. Xiao, N., Yin, M., Zhang, L., Qu, X., Du, H., Sun, X., et al. (2009). Tumor necrosis factor-alpha deficiency retards early fatty-streak lesion by influencing the expression of inflammatory factors in apoE-null mice. Mol. Genet. Metab. 96, 239-244. doi: 10.1016/j.ymgme.2008.11.166.
153. Xu, L., Kitade, H., Ni, Y., and Ota, T. (2015). Roles of chemokines and chemokine receptors in obesity-associated insulin resistance and nonalcoholic fatty liver disease. Biomolecules 5, 1563-1579. doi: 10.3390/biom5031563.
154. Yadav, A., Saini, V., and Arora, S. (2010). MCP-1: chemoattractant with a role beyond immunity: a review. Clin. Chim. Acta 411, 1570-1579. doi: 10.1016/j.cca.2010.07.006.
155. Yamagishi, S. I., Edelstein, D., Du, X. L., Kaneda, Y., Guzmán, M., and Brownlee, M. (2001). Leptin induces mitochondrial superoxide production and monocyte chemoattractant protein-1 expression in aortic endothelial cells by increasing fatty acid oxidation via protein kinase A. J. Biol. Chem. 276, 25096-25100. doi: 10.1074/jbc. M007383200.
156. Yamauchi, T., Kamon, J., Ito, Y., Tsuchida, A., Yokomizo, T., Kita, S., et al. (2003a). Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 423:6941. doi: 10.1038/nature01705.
157. Yamauchi, T., Kamon, J., Waki, H., Imai, Y., Shimozawa, N., Hioki, K., et al. (2003b). Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis. J. Biol. Chem. 278, 2461-2468. doi: 10.1074/jbc. M209033200.
158. Yamauchi, T., Kamon, J., Waki, H., Terauchi, Y., Kubota, N., Hara, K., et al. (2001). The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat. Med. 7, 941-946. doi: 10.1038/90984.
159. Yamauchi, T., Nio, Y., Maki, T., Kobayashi, M., Takazawa, T., Iwabu, M., et al. (2007). Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions. Nat. Med. 13, 332-339. doi: 10.1038/nm1557.
160. Yudkin, J. S., Eringa, E., and Stehouwer, C. D. (2005). "Vasocrine" signalling from perivascular fat: a mechanism linking insulin resistance to vascular disease. Lancet 365, 1817-1820. doi: 10.1016/S0140-6736(05)66585-3.
161. Zeidan, A., Purdham, D. M., Rajapurohitam, V., Javadov, S., Chakrabarti, S., and Karmazyn, M. (2005). Leptin induces vascular smooth muscle cell hypertrophy through angiotensin II-and endothelin-1-dependent mechanisms and mediates stretch-induced hypertrophy. J. Pharmacol. Exp. Ther. 315, 1075-1084. doi: 10.1124/jpet.105.091561.
162. Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., and Friedman, J. M. (1994). Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425-432. doi: 10.1038/372425a0.
163. Zhang, Y., Yang, X., Bian, F., Wu, P., Xing, S., Xu, G., et al. (2014). TNFa promotes early atherosclerosis by increasing transcytosis of LDL across endothelial cells: crosstalk between NF-γB and PPAR-γ. J. Mol. Cell. Cardiol. 72, 85-94. doi: 10.1016/j.yjmcc.2014.02.012.
164. Zhu, W., Cheng, K. K. Y., Vanhoutte, P. M., Lam, K. S. L., and Xu, A. (2008). Vascular effects of adiponectin: molecular mechanisms and potential therapeutic intervention. Clin. Sci. 114, 361-374. doi: 10.1042/CS20070347.