Obesity-related glomerulopathy and podocyte injury: A mini review

Frontiers in Bioscience - Elite

Volumn 4 E, Issue 3, 2012, Pages 1058-1070

  Camici, Marcello ^a   Galetta, Fabio ^a   Abraham, Nader ^b   Carpi, Angelo ^a  

^a UNIVERSITY OF PISA   (Italy)

^b MEDICAL COLLEGE OF OHIO   (United States)

Author keywords

Obesity related glomerulopathy; Podocyte injury; Proteinuria podocytes; Review

Indexed keywords

ADIPONECTIN; ALDOSTERONE; ANGIOTENSIN 2 RECEPTOR ANTAGONIST; ANGIOTENSIN II; ANTIINFLAMMATORY AGENT; ANTIOXIDANT; CYTOKINE; ENZYME INHIBITOR; FARNESOID X RECEPTOR; HEME OXYGENASE; PLASMINOGEN ACTIVATOR INHIBITOR 1; TUMOR NECROSIS FACTOR INHIBITOR;

ARTICLE; FOCAL GLOMERULOSCLEROSIS; GLOMERULOPATHY; HUMAN; HYPERLIPIDEMIA; INFLAMMATION; LIPID METABOLISM; MACROPHAGE; NONHUMAN; OBESITY; OBESITY RELATED GLOMERULOPATHY; OXIDATIVE STRESS; PATHOGENESIS; PODOCYTE; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; GLOMERULUS; PATHOLOGY; PATHOPHYSIOLOGY; REVIEW;

HUMANS; KIDNEY GLOMERULUS; OBESITY; PODOCYTES;

EID: 84860849413     PISSN: 19450494     EISSN: 19450508     Source Type: Journal    
DOI: None     Document Type: Article

References (144)

1. T.S.L.Visscher, J.C. Seidell: The public health impact of obesity. Ann Rev Public Health 22, 355-375 (2001). (Pubitemid 32452512)
2. M.P. O'Donnell , B.L. Kasiske, M.P. Cleary, W.F. Keane: Effects of genetic obesity on renal structure and function in the Zucker rat.II. Micropuncture studies. J Lab Clin Med 106,605-610 (1985)
3. B.L Kasiske, J. Napler: Glomerular sclerosis in patients with massive obesity. Am J Nephrol 5,45-50 (1985) (Pubitemid 15195137)
4. J.R. Nyengaard, T.F. Bendtsen: Glomerular number and size in relation to age,kidney weight and body surface in normal man. Anat Rev 232,194-201 (1992)
5. D.E. Wessen, N.A. Kurtzman, J. Pedro Frommer: Massive obesity and nephrotic proteinuria with a normal biopsy. 40,235-237 (1985)
6. J.C. Jennette, L. Charles, W. Grubb: Glomerulomegaly and focal segmental glomerulosclerosis associated with obesity and sleep apnea syndrome. Am J Kid Dis 10,470-472 (1987) (Pubitemid 18007347)
7. N. Kambham, G.S. Markowitz, A.M. Valeri, J. Lin, V.D. D'Agati: Obesity-related glomerulopathy:an emerging epidemi. Kid Int 59,1498-1509 (2001)
8. A. Chagnac, T. Weinstein, A. Korzets: Glomerular hemodynamics in severe obesity. Am J Physiol renal Physiol 278, F817-F822 (2000) (Pubitemid 30351084)
9. M. Praga, E. Hernandez, E. Morales: Clinical features and long-term outcome of obesity-associated focal segmental glomerulosclerosis. Nephrol Dial Trannspl 16, 1790-1798 (2001) (Pubitemid 32821410)
10. M. Praga, E. Hernandez, A. Andres: Effects of body weight loss and captopril treatment on proteinuria associated with obesity. Nephron 70, 35-41 (1995)
11. R.D. Adelman: Obesity and renal disease. Curr Opin Nephrol Hypert 11, 331-335 (2002) (Pubitemid 34496782)
12. J. Wang, X. Chen, Y. Song, B. Caballero, L.J. Cheskin:Association between obesity and kidney disease: a systematic review and meta analysi. Kid Int 73,19-33 (2008) (Pubitemid 350273639)
13. E. Ritz, N. Kolegonova: Obesity and chronic kidney disease. Semin Nephrol 29, 504-511 (2010)
14. B.L. Kasiske, A.J. Umen: The influence of age,sex,race and body habitus on kidney weight in humans. Arch Pathol Lab Med 110,55-60 (1986) (Pubitemid 16011812)
15. B.L. Kasiske, M.P. O'Donnell, W.F. Keane: The Zucker rat model of obesity,insulin resistance,hyperlipidemia and renal injury. Hypertension Supp I,I110-I115 (1992)
16. A.D. Dobrian, M.J. Davies, R.L. Prewitt, T.J. Lanterio: Development of hypertension in a rat model of diet-induced obesity. Hypertension 35,1009-1015 (2000) (Pubitemid 30303966)
17. T. Jiang, Z. Wang, G. Proctor, S. Morkowitz: Dietinduced obesity in C57BL/6J mice causes increased renal lipid accumulation and glomerulosclerosis via a sterol regulatory element-binding protein-1c-dependent pathway. J Biol Chem 280, 32317-32325 (2005) (Pubitemid 41361841)
18. A.H. Cohen: Massive obesity and the kidney. Am J Pathol 81,117-130 (1975)
19. E. Morales, M.A. Valero, M. Leon, E. Hernandez, M. Praga:Beneficial effects of weight loss on overweight patients with chronic proteinuric nephropathies. Am J Kid Dis 41,319-327 (2003) (Pubitemid 36152449)
20. C.Y. Hsu, C.E. McCulloch; C. Iribarren: Body mass index and risk for end-stage renal disease. Ann Int Med 144,21-28 (2006) (Pubitemid 46780716)
21. P.S. Thorner, M. Ho, V. Eremina, Y. Sado, S. Quaggin: Podocytes contribute to the formation of glomerular crescents. J Am Soc Nephrol19,495-502 (2008) (Pubitemid 351355393)
22. J. Bariety, P. Bruneval, A. Meyrier, C. Mandet, C. Jacquot: Podocyte involvement in human immune crescentic glomerulonephritis. Kid Int 68,1109-1119 (2005) (Pubitemid 43246427)
23. H.M. Chen, Z.H.Liu, C.I. Zeng, S.H. LI, Q.W. Wang, S.H.Li: Podocyte lesions in patients with obesity-related glomerulopathy. Am J Kid Dis 48, 772-779 (2006)
24. U. Schorr, K. Blaschke, S. Turan: Relationship between angiotensinogen,leptin and blood pressure levels in young normotensive men. J Hypert16,1475-1480 (1998) (Pubitemid 28470495)
25. R.C. Frederich, B.B. Kahn, M.J. Pesch, J.S.Flier: Tissue specific nutritional regulation of angiotensinogen in adipose tissue. Hypertension 19,339-344 (1992)
26. P. Sharma, R. Sharma, A.S. Greene, E.T. McCarthy, V.S.Savin:Documentation of angiotensinogen II receptors in glomerular epithelial cells. Am J Physiol Renal Physiol 274, F623-F627 (1998)
27. T.B. Huber, J. Gloy, A. Henger: Catecholamines modulate podocyte function. J Am Soc Nephrol 9, 335-345 (1998) (Pubitemid 28122858)
28. H. Pavenstadt, W. Kritz, M. Kretzler: Cell biology of the glomerular podocyte. Physiol Rev 83, 253-307 (2003) (Pubitemid 36459882)
29. A. Patel, R. Sharif-Naeini, J.R.H.Folgering, D. Bichet, F. Duprat, E. Honorè:Canonical TRP channels and mechanotransduction:from physiology to diseases states. Pfluf Arch Eur J Physiol 460,571-81 (2010)
30. J. Reiser, K.R. Polu, C.C. Moller: TRCP6 is a glomerular slit diaphragm-associated channel required for normal renal function. Nat Genet 37,739-744 (2005) (Pubitemid 41754891)
31. C.C. Moller, C. Wei, M.M. Altintas: Induction of TRCP6 channel in acquired forms of proteinuric kidney disease. J Am Soc Nephrol 18,29-36 (2007) (Pubitemid 46053419)
32. C. Faul, K. Asanuma,E. Yanagida-Asanuma, K. Kim, P. Mundel: Actin up: regulation of podocyte structure and function by components of the actin cytoskeleton. Trends in Cell Biology 17,428-437 (2007) (Pubitemid 47499042)
33. J. Gloy, A. Henger, G.K. Fischer:Angiotensin II depoolarizes podocytes in the intact glomerular of the rat. J Clin Invest 99,2772-2781 (1997) (Pubitemid 27259825)
34. A. Henger, T. Huber, K.G. Fischer:Angiotensin II increases the cytosolic calcium activity in rat podocytes in culture. Kid Int 52, 687-693 (1997) (Pubitemid 27402367)
35. M. Nagase, T. Fujita: Aldosterone and glomerular podocyte injury. Clin Exp Nephrol12,233-242 (2008)
36. R.B. De Paula, A.A. Da Silva, J.E.Hall: Aldosterone anatogonism attenuates obesity-induced hypertension and glomerular hyperfiltration. Hypertension 43,41-47 (2004) (Pubitemid 38031909)
37. A.S. Bomback, P.J. Klemmer: Renal injury in extreme obesity: the important role of aldosterone. Kid Int 74,1216-1217 (2008)
38. T.L. Goodfriend, D.L.Ball, B.M. Egan: Epoxy-kedto derivative of linoleic acid stimulates aldosterone secretion. Hypertension 43,358-363 (2004) (Pubitemid 38174139)
39. K.Y.Kim, J.H. Kim, C.H. Lee, D.H. Kim, S.H. Han, Y. Yang: Tumor necrosis factor-alpha and interleukin-1beta increases CTRP1 expression in adipose tissue. FEBS Lett.580,3953-3960 (2006) (Pubitemid 43946893)
40. J.H. Jeon,K.Y. Kim, J.H.Kim, A. Baek, H. Cho, J.W. Kim, S.H .Han, J.S. Lim, Y.Yang: A novel adipokine CTRP1 stimulates aldosterone production. FASEB J.22, 1502-1511 (2008) (Pubitemid 351656790)
41. S. Shibata, M. Nagase, S. Yoshida, I. Kawachi, T. Fujita: Podocyte as the target for aldosterone.Roles of oxidative stress and SgK1. Hypertension 49, 355-364 (2007) (Pubitemid 46143013)
42. I. Guney: Antifibrotic effects of aldosterone receptor blocker (spironolactone) in patients with chronic kidney disaease. Renal Failure 31, 779-784 (2009)
43. A. Whaley-Connell, J. Habibi, Y.Wei: Mineralcortocoid receptor antagonism attenuates glomerular filtration barrier remodeling in the transgenic Ren2 rat. Am J Physiol Renal Physiol 296, F1013-F1022 (2009)
44. R.B. de Paula, A. da Silva, J.E. Hall: Aldosterone antagonism attenuates obeisty-induced hypertension and glomerular hyperfiltration. Hypertension 43,41-47 (2004) (Pubitemid 38031909)
45. L.J. Ma, A.B. Fogo: PAI-1 and kidney fibrosis. Front Biosc 14,2028-2041 (2009)
46. D.J. Loskutoff, J.P. Quigley: PAI-1,fibrosis and the elusive provisional fibrin matrix. J Clin Invest 106,1441-1443 (2000) (Pubitemid 32038581)
47. L.J. Ma, S.L. Mao, K.L.Taylor: Prevention of obesity and insulin resistance in mice lacking plasminogen activator inhibitor 1. Diabetes 53,336-346 (2004) (Pubitemid 38174548)
48. X. Liang, T. Kanjanabuch, S.L. Mao: Plasminogen activator inhibitor-1 modulates adipocyte differentiation.Am J Physiol Endocrinol Metab 290,E103-E113 (2006)
49. P. Kishore, W. Li, J. Tonelli, D. Lee, S. Koppaka, M. Hawkins: Adipocyte-derived factors potentiate nutrientinduced production of plasminogen activator inhibitor-1 by macrophages. Sci Transl Med 24, 20ra15 (2010)
50. H.S. Lee, S.Y. Park, K.C. Moon, S.Y. Hong: mRNA expression of urokinase and plasminogen activator inhibitor-1 in human crescentic glomerulonephritis. Histop 39,203-209 (2001) (Pubitemid 34225048)
51. K. Hamano, M. Iwano, Y. Akai, Y. Yoshida, S. Kohono, K. Dohi: Expresion of glomerular plasminogen activator inhibitor type 1 in glomerulonephritis. Am J Kid Dis 39,695-705 (2002) (Pubitemid 34263342)
52. T. Nakamura, N. Tanaka, N. Higuma, S.Yokota: The localization of plasminogen activator inhibitor-1 in glomerular subepithelial deposits in membranous nephropathy. J Am Soc Nephrol 7,2434-2444 (1996) (Pubitemid 27465951)
53. P. Paueksakon, M.P. Revelo,A.B. Fogo: Microangiopathic injury and augmented PAI-1 in human diabetic nephropathy. Kid Int 61, 2142-2148 (2002) (Pubitemid 34539331)
54. A.A. Eddy, A.B. Fogo: Plasminogen activator inhibitor-1 in chronic kidney disease: evidence and mechanism of action. J Am Soc Nephrol 17,2999-3012 (2006) (Pubitemid 44707760)
55. J. Yuan, R. Jia, Y. Bao: Aldosterone up-regulates production of plasminogen activator inhibitor-1 by renal mesangial cells. J Biochem Mol Biol 40, 80-188 (2007)
56. G.A. Francis, R.H. Knopp, J.F. Oram : Nuclear receptors and the control of metabolism. Annu Rev Physiol 65;261-311 (2003) (Pubitemid 38249155)
57. H.C.Yang, L.J. Ma, A.B. Fogo: Peroxisome proliferator-activated receptor-gamma agonist is protective in podocyte injury-associated sclerosis. Kid Int 69,1756-1764 (2006) (Pubitemid 43739202)
58. T. Naito, L.J.Ma, H.Yang, Y. Zuo, A.B. Fogo: Angiotensin II receptor actions contribute to angiotensin type 1 receptor blocker effects on kidney fibrosis. Am J Physiol Renal Physiol 298,F683-F691 (2010)
59. A. Gils, P.J.Declerck: Plasminogen activator inhibitor-1. Curr Med Chem 11, 323-2334 (2004)
60. S.P.Bagby: Obesity-initiated metabolic syndrome and the kidney:a recipe for chronic kidney disease? J Am Soc Nephrol 15,2775-2791 (2004) (Pubitemid 41103387)
61. N. Deji, S. Kume, S. Araki: Structural and functional changes in the kidneys of high-fat diet-induced obese mice. Am J Physiol Renal Physiol.296,F118-F126 (2009)
62. E. Reisin, P.J. Ebenezer, J. Liao: Effect of the HMGCoA reductase inhibitor rosuvastatin on early chronic kidney injury in obese Zucker rats fed with an atherogenic diet. Am J Med Sci 338,301-309 (2009)
63. E. Santini, R. Lupi, S. Baldi: Effects of different LDL particles on inflammatory molecules in human mesangial cells. Diabetologia 51, 2117-2125 (2008)
64. M. Tomiyama-Hanayama, H. Rakugi, V. Fonsato: Effect of interleukin-6 receptor blockage on renal injury in apolipoprotein E-deficient mice. AmJPhysiolRenalPhysiol. 297, F679-F684 (2009)
65. B. Bussolati, M.C. Deregibus, V. Fonsato: Statins prevent oxidized LDL-induced injury of glomerular podocytes by activating the phosphatidyilinositol 3-kinase/Akt-signaling pathway. JamSocNephrol 16, 936-1947 (2005)
66. F.C. Cormack-Aboud, P.T. Brinkkoetter, J.W.Pippin: Rosuvastatin protects against podocyte apoptosis in vitro.Nephrol Dial Transpl 24,404-412 (2009)
67. R.Lennon, D. Pons, M.A. Sabin, C. Wei, J.P.Shield, R.J. Coward: Saturated fatty acids induce insulin resistance in human podocytes:implications for diabetic nephropathy. Nephrol Dial Transpl 24,288-3296 (2009)
68. L. Sun, N. Halaihelk, W. Zhang: Role of sterol regulatory element-binding protein 1 in regulation of renal lipid metabolism and glomerulosclerosis in diabetes mellitus. J.Biol.Chem. 277,18919-18927 (2002) (Pubitemid 34952453)
69. T. Jiang, Z. Wang, G. Proctor: Diet-induced obesity in C57BL/6J mice causes increased renal accumulation and glomerulosclerosis via a sterol regulatory element-binding protein-1c-dependent pathway. J.Biol.Chem. 280, 32317-32395 (2005)
70. X.X. Wang, T. Jiang, Y. Shen: The farnesoid X receptor modulates renal lipid metabolism and dietinduced renal inflammation, fibrosis, and proteinuria. Am. J. Physiol. Renal.Physiol. 297, F1587-F1596 (2009)
71. Y.Wu, Z. Liu, Z. Xiang: Obesity-related glomerulopathy:insights from gene expression profiles of the glomeruli derived from renal biopsy samples. Endocrinology 147, 44-50 (2006) (Pubitemid 43004261)
72. T. Yatagai: Hypoadiponectinemia is associated with visceral fat accumulation and insulin resistance in Japanese men with type 1 diabetes mellitus. Metabolism 52,1274-1278 (2003) (Pubitemid 37351094)
73. C. Swallow C, J. Dennis: Alpha2HS-glycoprotein,an antagonist of transforming growth factor beta in vivo,inhibits intestinal tumor progression. Cancer Res. 64,6402-6409 (2004) (Pubitemid 39297893)
74. J.H. Ix, K. Sharma: Mechanisms linking obesity,chronic kidney disease and fatty liver disease: the roles of fetuin-A,adiponectin and AMPK. J. Am. Soc.Nephrol. 21,406-412 (2010)
75. A. Schaffler, U. Muller-ladner, J. Sclomerich, C. Buchler: Role of adipose tissue as an inflammatory organ in human disease. Endocrine Rev 27, 449-467 (2006) (Pubitemid 44213227)
76. E.E. Kershaw, J.S. Flier: Adipose tissue as an endocrine organ. J. Clin. Endocr.Metab. 89, 2548-2556 (2004) (Pubitemid 38766330)
77. R.H. Straub, M. Cutolo, F. Buttgereit, G. Pongratz: Energy regulation and neuroendocrine-immune control in chronic inflammatory diseases. J.Int. Med. doi 10.1111/j,1365-2796 (2010)
78. H. Tilg, A.R. Moschen: Adipocytokines:meddiators linking adipose tissue,inflammation and immunity. Nature Immun. 6, 773-783 (2006)
79. F. Simpson, J.P. Whitehead: Adiponectin-It's all about the modifications. Int.J.Biochem.Cell Biol. 42, 785-788 (2010)
80. T. Yamauchi, J. Kamon, Y. Ito, M. Tsuchida: Cloning of adiponectin receptors that mediate antidiabetic affects. Nature 423,762-769 (2003) (Pubitemid 36735700)
81. T. Kadowaki, T. Yamauchi, N. Kubota, K. Hara: Diponectin and adiponectin receptors in insulin resistance, diabetes and the metabolic syndrome. J. Clin. Invest. 116,1784-1792 (2006) (Pubitemid 44033298)
82. X. Mao, C.K. Kikani, R.A. Rijas, P. Langlais, L. Wang, F.J. Ramos: APPL1 binds to adiponectin receptors and mediates adiponectin signalling and function. Nature Cell Biology 8,516-523 (2006)
83. T. Kadowaki, T. Yamauchi, N. Kubota: The physiological and pathophysiological role of adiponectin receptors in the peripheral tissues and CNS. FEBS Lett. 582,74-80 (2008) (Pubitemid 50012818)
84. P.G. Cammisotto, M. Bendayan: Adiponectin stimulates phosphorylation of AMP-activated protein kinase alpha in renal glomeruli. J.Mol.Histol. 39; 579-584 (2008)
85. K. Sharma, S. Ramachadraro, G. Qiu: Adiponectin regulates albuminuria and podocyte function in mice. J. Clin. Invest. 118, 1645-1656 (2008) (Pubitemid 351632369)
86. K. Ohashi, H. Iwatani, S. Kihara: Exacerbation of albuminuria and renal fibrosis in subtotal renal ablation model of adiponectin-knochout mice. Arterioscl.Thromb.Vasc.Biol. 27,1910-1917 (2007) (Pubitemid 47312299)
87. K. Sharma: The link between obesity and albuminuria:adiponectin and podocyte dysfunction. Kid.Int.76t,145-148 (2009)
88. R.S. Ahima: Linking adiponectin to proteinuria. J. Clin. Invest. 118, 1619-1622 (2008) (Pubitemid 351632364)
89. C. Zoccali, F. Mallamaci: Obesity, diabetes, adiponectin: a podocyte affair? Nephrol.Dial.Transpl.23, 3767-3770 (2008)
90. K.E,. Wellen, G.S. Hotarnisligil: Inflammation,stress and diabetes. J. Clin. Invest.115,1111-1119 (2005)
91. S.P. Weisberg, D. McCann, M.Desai: Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest. 112,1796-1808 (2003) (Pubitemid 38063703)
92. H. Xu, G.T. Barnes, O. Yang: Chronic inflammation in fat plays a crucial role in the development of obesityrelated insulin resistance. J. Clin. Invest. 112,1821-1830 (2003) (Pubitemid 38063705)
93. S. Gordon, P.R. Taylor: Monocyte and macrophage heterogeneity. Nat.Rev.Immunol. 5,953-964 (2005) (Pubitemid 41746764)
94. S.D. Ricardo, H. van Goor, A.A.Eddy: Macrophage diversity in renal injury and repair. J. Clin. Invest. 118, 3522-3530 (2008)
95. D.C. Kluth: Pro-resolution properties of macrophages in renal injury. Kid.Int.72, 234-236 (2007) (Pubitemid 47172382)
96. S. Gordon: Alternative activation of macrophages. Nat.Rev.Immunol. 3, 23-35 (2003) (Pubitemid 37328697)
97. C.N. Lumeng, J.L. Bodzin, A.R. Saltiel: Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J. Clin. Invest.117, 175-184 (2007) (Pubitemid 46048464)
98. .C.N. Lumeng, J.B. Del Proposto, D.J. Westcott, A.R. Saltiel: Phenotype switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophages subtypes. Diabetes 57, 3239-3246 (2008)
99. J.S. Duffield, P.G. Tipping, T. Kipari: Conditional ablation of macrophages halts progression of crescentic glomerulonephritis. Am. J. Pathol.167,1207-1219 (2005) (Pubitemid 41541408)
100. Y. Wang, Y.P. Wang, G. Zheng: Ex vivo programmed macrophages ameliorate experimental chronic inflammatory renal disease. Kid.Int. 72, 290-299 (2007) (Pubitemid 47172367)
101. D.L. Lee, R. Leite, C. Fleming: Hypertensive response to acute stress is attenuated in interleukin-6 knockout mice. Hypertension 44, 259-263 (2004) (Pubitemid 39167220)
102. J. Hirosumi: A central role for JNK in obesity and insulin resistance. Nature 420, 333-336 (2002) (Pubitemid 35398190)
103. M. Yuan: Reversal of obesity and diet-induced insulin resistance with salycilates or targeted disruption of IKKbeta. Science 293,1673-1677 (2001) (Pubitemid 32807849)
104. U. Ozcan: Endoplasmic reticulum stress links obesity,insulin action and type 2 diabetes. Science 306, 457-461 (2004) (Pubitemid 39372439)
105. S. Furukawa: Increased oxidative stress in obesity and its impact on metabolic syndrome J. Clin. Invest. 114,1752-1761 (2004) (Pubitemid 40385531)
106. H.Shi: TLR4 links innate immunity and fatty acidinduced insulin resistance. J. Clin Invest. 116,3015-3025 (2006) (Pubitemid 44684486)
107. Y. Ikezumi, T. Suzuki, T. Karasawa: Activated macrophages down-regulate podocyte nephrin and podocin expression via stress-activated protein kinases. Biochem.Biophys.Res.Comm. 376,706-711 (2008)
108. Y. Takano, H. Yamauchi, K. Kayakawa, N.Hramatsu: Transcriptional suppression of nephrin in podocytes by macrophages:roles of inflammatory cytokines and involvement of the PI3K/Akt pathway. FEBS Lett.581, 421-426 (2007) (Pubitemid 46149613)
109. Y.Saito, M. Okamura, S. Nakajima, K. Hayakawa: Suppression of nephrin exprtession by TNF-alpha via interfering with the cAMP-retinoic acid receptor pathway. Am. J. Physiol. Renal Physiol. 298, F1436-F1444 (2010)
110. S.B. Koukouritaki, E.A.Vardaki, E.A. Papakonstanty, E. Lianos: TNF-alpha induces actin cytoskeleton reorganization in glomerular epithelial cells involving tyrosine phosphorylation of paxillin and focal adhesion kinase. Mol.Med. 5, 382-392 (1999) (Pubitemid 29382312)
111. M.C. Banas, B. Banas, L. Hudkins, T.A. Wietecha: TLR4 links podocytes with the innate immune system to mediate glomerular injury. J. Am. Soc.Nephrol. 19, 704-713 (2008)
112. M.V. Potenza, J.L. Mechanick: The metabolic syndrome:definition,global impact and pathophysiology. Nutr.Clin Pract. 24,560-577 (2009)
113. P.N. Chander, O.Gealekman, S.V. Brodsky: Nephropathy in Zucker diabetic fat rat is associated with oxidative and nitrosattive stress :prevention by chroni therapy with a peroxynitrate scavenger ebselen. J. Am. Soc.Nephrol. 15, 2391-2403 (2004) (Pubitemid 39159339)
114. M. Nangaku, Y. Izuhara, N. Usuda: Type 2 diabetic nephropathy rat model,the improvement of obesity by a low caloric diet reduces oxidative/carbonyl stress and prevents diabetic nephropathy. Nephrol.Dial.Transpl. 20, 2661-2669 (2005) (Pubitemid 41672264)
115. Y. Wu, Z.Liu, Z. Xiang: Obesity-related glomerulopathy:insights from gene expression profiles of the glomeruli derived from renal biposy samples. Endocrinology 147, 44-50 (2006) (Pubitemid 43004261)
116. N.G. Abraham, J. Cao, D. Sacerdoti, X. Li, G. Drummond: Heme oxygenase: the key to renal function regulation. Am. J. Physio.Renal Physiol 297, F1137-:F1152 (2009)
117. I. Cruse, M.D. Mainess: Evidence suggesting that two forms of heme oxygenase are products of different genes. J.Biol.Chem. 263, 3348-3353 (1988) (Pubitemid 18072793)
118. N.G. Abraham, A. Kappas: Heme oxygenase and the cardiovascular-renal system. Free Rad.Biol.Med. 39, 1-25 (2005) (Pubitemid 40733115)
119. S.J. Peterson, W.H. Frishman, N.G. Abraham: Targeting heme oxygenase: therapeutic implications for diseases of the cardiovascular system. Cardiol.Rev. 17, 99-111 (2009)
120. M. Li, D.H. Kim, P.L. Tsenovoy, S.J. Peterson, R. Rezzani, L.F. Rodella, W.S. Aronow, S. Ikehara, N.G. Abraham: Treatment of obese diabetic mice with a heme oxygenase inducer reduces visceral and subcutaneous adiposity,increases adiponectin levels,improves insulin sensitivity and glucose tolerance. Diabetes 57, 1526-1535 (2008)
121. J. Reiser, P. Mundel: Dual effects of RAS blockade on blood pressure and podocyte function. Current Hypert Rep 9: 403-408 (2007)
122. M. Camici, A. Carpi, G. Cini, F. Galetta, N. Abraham. Podocyte dysfunction in aging -related glomerulosclerosis. In press on FBS
123. J.A. Wilmer, B.H. Rovin, C.J. Hebert: Management of glomerular proteinuria; a commentary. J. Am. Soc.Nephrol. 14, 3217-3232 (2003)
124. P. Rutkowski, A. Klassen, K. Sebekova: Renal disease in obesity the need for greater attention. J. Ren Nutr 16:216-223 (2006) (Pubitemid 43975009)
125. D.W. Lee, I.S. Kwak, S.B. Lee, S.H. Song, E.Y. Seong, H.C. Chung, B.Y. Yang, M.Y. Lee, M.Y.Sol: Effects of colecoxib and nordihydroguaiaretic acid on puromycin aminonucleoside-induced nephrosis in the rat. J Korean Med Sci. 24 Suppl, S183-8 (2009)
126. R.M. Carey, Z.Q. Wang, H.M. Siragy: Role of the angiotensin type2 receptor in the regulation of blood pressure and renal function. Hypertension 35, :155-63 (2000) (Pubitemid 30054167)
127. A.D. Struthers: Aldosterone blockade in cardiovascular disease. Heart. 90, 1229-1234 (2004) (Pubitemid 39279920)
128. L.J. Ma, S. Nakamura, J.C. Aldigier, A.B. Fogo:Regression of glomerulosclerosis with high-dose angiotensin inhibition is linked to decreased plasminogen activator inhibitor-1. J. Am. Soc.Nephrol. 16, 966-976 (2005) (Pubitemid 41710307)
129. B. Bussolati, M.C. Deregibus, V. Fonsato, S. Doublier, G. Camussi: Statins prevents oxidized LDLinduced injury of glomerular podocytes by activating the posphatidylinositol 3-kinase/AKT-signaling pathway. J. Am. Soc.Nephrol. 16, 1936-1947 (2005) (Pubitemid 41716424)
130. K. Jalovaara, M. Santaniemi, M. Timonen, J. Jokelainen, Y.A. Kesaniemi, O. Ukkola, S. Keinanen-Kiukaanniemi, U. Rajala: Low serum adiponenctin levels as a predictor of impaired glucose regulation and type 2 diabetes mellitus in a middle-aged Finnish population. Metabolism 57, 1130-1134 (2008) (Pubitemid 351982026)
131. P. Linscheld, M. Christ-Crain, R. Stoeckli: Increase in high molecular wieght adiponectin by bariatric surgeryinduced weight. Loss Diabetes Obes.Metab. 10, 1266-1270 (2008)
132. A.Serra, M.L. Granada, R. Romero, B. Bayes, A. Cantona, J. Bonet:The effect of bariatric surgery on adipocytokines,renal parameters and other cardiovascular risk factors in severe and very severe obesity:1-year follow up. Clin.Nutr. 23, 400-408 (2006) (Pubitemid 44182760)
133. C.H. Kim, P. Pennisi, H. Zhao, D. LeRoth: MKR mice are resistant to the metabolic actions of both insulin and adiponectin: discordance between insulin resistance and adiponectin responsiveness. Am. J. Physiol. Endocrinol.Metab. 291, E298-E305 (2006) (Pubitemid 44035289)
134. P. Restituto, I. Colina, J.J. Varo, N. Varo: Adiponectin diminishes platelet aggregation and sCD40L release.Potential role in metabolic syndrome. .J.Physiol.Endocrin.Met. 298, E1072-E1077 (2010)
135. G. Zhou, R. Myers, Y. Li: Role of AMP-activated protein kinase in mechanism of metformin action. J. Clin. Invest. 108, 1167-1174 (2001) (Pubitemid 32995375)
136. T. Kanjanbuch, L.J. Ma, J. Chen: PPAR-gamma agonist protects podocytes from injury. Kid.Int. 71,1232-1239 (2007) (Pubitemid 46884258)
137. C.H. Lee, M.R. Olson: Minireview:lipidi metabolism.metabolic diseases and peroxisome proliferator-activated receptors. Endocrinology 144, 2201-2207 (2003)
138. A. Israel: The IKK complex:an integrator of all signals that activate NF-kB? Trends in Cell Biology 10, 129-133 (2000) (Pubitemid 30171300)
139. E.N. Wardle: Nuclear factor kB for the nephrologist. Nephrol.Dial. Transpl.16,1764-1768 (2001)
140. C. Guijarro, J. Egido: Trnscription factor kB(NF-kB) and renal disease. Kid.Int. 59, 415-424 (2001) (Pubitemid 32157906)
141. N. Yamaguchi, J.G.M. Argueta, Y. Mashiro, M. Yamashita: Adiponectin inhibits Toll-like receptor familyinduced signaling. FEBS Letters 579, 6821-6826 (2005) (Pubitemid 41773693)
142. P. Juncos, J.P. Grande, N. Murali, K.A. Nath: Bilirubin is an antioxidant of possible physiological importance. Science 235, 1043-1046 (1987)
143. D.H. Kim, A.P. Burgess, M. Li, N.G. Abraham: Heme oxygenase-mediated increases in adiponectin decrease fat content and inflammatory cytokines,tumor necrosis factoralpha and interleukin-6 in Zucker rats and reduces adipogenesis in human mesenchymal stem cells. J.Pharmacol Exp.Ther. 325, 833-840 (2008) (Pubitemid 351724315)
144. A. Nicolai A, M. Li, D.H. Kim, S.J. Peterson, N.G. :Heme oxygenase-1 induction remodels adipose tissue and improves insulin sensitivity in obesity-induced diabetic rats. Hypertension 53, 508-515 (2009)