Lipid biology of the podocyte-new perspectives offer new opportunities

Nature Reviews Nephrology

Volumn 10, Issue 7, 2014, Pages 379-388

  Fornoni, Alessia ^a   Merscher, Sandra ^a   Kopp, Jeffrey B ^b  

^a UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

^b NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ABC TRANSPORTER; APOLIPOPROTEIN; ARACHIDONIC ACID; AUTOANTIBODY; FATTY ACID; GLYCEROPHOSPHOLIPID; HIGH DENSITY LIPOPROTEIN; LIPID; PHOSPHOLIPASE A2; SPHINGOMYELIN PHOSPHODIESTERASE;

CELL FUNCTION; DIABETIC NEPHROPATHY; DISEASE PREDISPOSITION; FOCAL GLOMERULOSCLEROSIS; GLOMERULOPATHY; HUMAN; KIDNEY BIOPSY; MEMBRANOUS GLOMERULONEPHRITIS; PATHOGENESIS; PODOCYTE; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SEQUENCE ANALYSIS;

ANIMALS; APOLIPOPROTEINS; ATP BINDING CASSETTE TRANSPORTER 1; AUTOANTIBODIES; CHOLESTEROL; DIABETIC NEPHROPATHIES; GANGLIOSIDES; GLOMERULOSCLEROSIS, FOCAL SEGMENTAL; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; LIPID METABOLISM; LIPOPROTEINS, HDL; MEMBRANE MICRODOMAINS; PHOSPHATIDYLCHOLINE-STEROL O-ACYLTRANSFERASE; PHOSPHOLIPASES A2; PODOCYTES; RENAL INSUFFICIENCY, CHRONIC; SIGNAL TRANSDUCTION; SPHINGOLIPIDS; SPHINGOMYELIN PHOSPHODIESTERASE;

EID: 84903551813     PISSN: 17595061     EISSN: 1759507X     Source Type: Journal    
DOI: 10.1038/nrneph.2014.87     Document Type: Review

References (144)

1. Fessler, M. B. & Parks, J. S. Intracellular lipid flux and membrane microdomains as organizing principles in inflammatory cell signalling. J. Immunol. 187, 1529-1535 (2011).
2. Schonholzer, K. W., Waldron, M. & Magil, A. B. Intraglomerular foam cells and human focal glomerulosclerosis. Nephron 62, 130-136 (1992).
3. Lee, H. S. & Kruth, H. S. Accumulation of cholesterol in the lesions of focal segmental glomerular sclerosis. Nephrology (Carlton) 8, 224-223 (2003).
4. Kao, W. H. et al. MYH9 is associated with nondiabetic end-stage renal disease in African Americans. Nat. Genet. 40, 1185-1192 (2008).
5. Kopp, J. B. et al. MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis. Nat. Genet. 40, 1175-1184 (2008).
6. Pays, E. et al. The trypanolytic factor of human serum. Nat. Rev. Microbiol. 4, 477-486 (2006). (Pubitemid 43771867)
7. Wang, X. X. et al. Diabetic nephropathy is accelerated by farnesoid X receptor deficiency and inhibited by farnesoid X receptor activation in a type 1 diabetes model. Diabetes 59, 2916-2927 (2010).
8. Merscher-Gomez, S. et al. Cyclodextrin protects podocytes in diabetic kidney disease. Diabetes 62, 3817-3827 (2013).
9. Tachibana, H. et al. Activation of liver X receptor inhibits osteopontin and ameliorates diabetic nephropathy. J. Am. Soc. Nephrol. 23, 1835-1846 (2012).
10. Kiss, E. et al. Lipid droplet accumulation is associated with an increase in hyperglycemia-induced renal damage: prevention by liver X receptors. Am. J. Pathol. 182, 727-741 (2013).
11. Herman-Edelstein, M., Scherzer, P., Tobar, A., Levi, M. & Gafter, U. Altered renal lipid metabolism and renal lipid accumulation in human diabetic nephropathy. J. Lipid Res. 55, 561-572 (2013).
12. Zador, I. Z. et al. A role for glycosphingolipid accumulation in the renal hypertrophy of streptozotocin-induced diabetes mellitus. J. Clin. Invest. 91, 797-803 (1993). (Pubitemid 23095252)
13. Najafian, B. et al. Progressive podocyte injury and globotriaosylceramide (GL-3) accumulation in young patients with Fabry disease. Kidney Int. 79, 663-670 (2011).
14. Beck, L. H. Jr. et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N. Engl. J. Med. 361, 11-21 (2009).
15. Fornoni, A. et al. Rituximab targets podocytes in recurrent focal segmental glomerulosclerosis. Sci. Transl. Med. 3, 85ra46 (2011).
16. Abi-Mosleh, L., Infante, R. E., Radhakrishnan, A., Goldstein, J. L. & Brown, M. S. Cyclodextrin overcomes deficient lysosome-to-endoplasmic reticulum transport of cholesterol in Niemann-Pick type C cells. Proc. Natl Acad. Sci. USA 106, 19316-19321 (2009).
17. Maxfield, F. R. & Wustner, D. Intracellular cholesterol transport. J. Clin. Invest. 110, 891-898 (2002).
18. Fielding, C. J. & Fielding, P. E. Cellular cholesterol efflux. Biochim. Biophys. Acta 1533, 175-189 (2001). (Pubitemid 33127270)
19. Brown, M. S. & Goldstein, J. L. A proteolytic pathway that controls the cholesterol content of membranes, cells and blood. Proc. Natl Acad. Sci. USA 96, 11041-11048 (1999). (Pubitemid 29487324)
20. Goldstein, J. L., DeBose-Boyd, R. A. & Brown, M. S. Protein sensors for membrane sterols. Cell 124, 35-46 (2006).
21. Peake, K. B. & Vance, J. E. Defective cholesterol trafficking in Niemann-Pick C-deficient cells. FEBS Lett. 584, 2731-2739 (2010).
22. Khera, A. V. et al. Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. N. Engl. J. Med. 364, 127-135 (2011).
23. Le Lay, S. et al. Cholesterol, a cell size-dependent signal that regulates glucose metabolism and gene expression in adipocytes. J. Biol. Chem. 276, 16904-16910 (2001). (Pubitemid 33657260)
24. Christian, A. E., Haynes, M. P., Phillips, M. C. & Rothblat, G. H. Use of cyclodextrins for manipulating cellular cholesterol content. J. Lipid Res. 38, 2264-2272 (1997). (Pubitemid 27495385)
25. Tang, C., Kanter, J. E., Bornfeldt, K. E., Leboeuf, R. C. & Oram, J. F. Diabetes reduces the cholesterol exporter ABCA1 in mouse macrophages and kidneys. J. Lipid Res. 51, 1719-1728 (2010).
26. Proctor, G. et al. Regulation of renal fatty acid and cholesterol metabolism, inflammation, and fibrosis in Akita and OVE26 mice with type 1 diabetes. Diabetes 55, 2502-2509 (2006). (Pubitemid 44871150)
27. Mulya, A. et al. Initial interaction of apoA-I with ABCA1 impacts in vivo metabolic fate of nascent HDL. J. Lipid Res. 49, 2390-2401 (2008).
28. Schwarz, K. et al. Podocin, a raft-associated component of the glomerular slit diaphragm, interacts with CD2AP and nephrin. J. Clin. Invest. 108, 1621-1629 (2001). (Pubitemid 33144872)
29. Huber, T. B. et al. Podocin and MEC-2 bind cholesterol to regulate the activity of associated ion channels. Proc. Natl Acad. Sci. USA 103, 17079-17086 (2006). (Pubitemid 44788925)
30. -/- mice with macrophage-specific transgenic expression of cholesteryl ester hydrolase: role of macrophage inflammation and infiltration into adipose tissue J. Biol. Chem. 285, 13630-13637 (2010).
31. Sorensson, J. et al. Glomerular endothelial fenestrae in vivo are not formed from caveolae. J. Am. Soc. Nephrol. 13, 2639-2647 (2002). (Pubitemid 35216032)
32. Zhang, G., Li, Q., Wang, L., Chen, Y. & Zhang, W. Interleukin-1β enhances the intracellular accumulation of cholesterol by up-regulating the expression of low-density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase in podocytes. Mol. Cell Biochem. 346, 197-204 (2011).
33. Mayrhofer, C. et al. Alterations in fatty acid utilization and an impaired antioxidant defense mechanism are early events in podocyte injury: a proteomic analysis. Am. J. Pathol. 174, 1191-1202 (2009).
34. Collins, A. J. et al. US Renal Data System 2013 Annual Data Report. Am. J. Kidney Dis. 63 (Suppl.) A7 (2014).
35. Parsa, A. et al. APOL1 risk variants, race, and progression of chronic kidney disease. N. Engl. J Med. 369, 2183-2196 (2013).
36. Duchateau, P. N. et al. Apolipoprotein L, a new human high density lipoprotein apolipoprotein expressed by the pancreas. Identification, cloning, characterization, and plasma distribution of apolipoprotein L. J. Biol. Chem. 272, 25576-25582 (1997). (Pubitemid 27438869)
37. Zhaorigetu, S., Wan, G., Kaini, R., Jiang, Z. & Hu, C. ApoL1, a BH3-only lipid-binding protein, induces autophagic cell death. Autophagy 4, 1079-1082 (2008).
38. Wan, G. et al. Apolipoprotein L1, a novel Bcl-2 homology domain 3-only lipid-binding protein, induces autophagic cell death. J. Biol. Chem. 283, 21540-21549 (2008).
39. Hartleben, B., Wanner, N. & Huber, T. B. Autophagy in glomerular health and disease. Semin. Nephrol. 34, 42-52 (2014).
40. Précourt, L. P. et al. The three-gene paraoxonase family: physiologic roles, actions and regulation. Atherosclerosism 214, 20-36 (2011).
41. Sreckovic, I. et al. Distinct composition of human fetal HDL attenuates its anti-oxidative capacity. Biochim. Biophys. Acta 1831, 737-746 (2013).
42. Araki, S. et al. Polymorphisms of human paraoxonase 1 gene (PON1) and susceptibility to diabetic nephropathy in type I diabetes mellitus. Diabetologia 43, 1540-1543 (2000). (Pubitemid 32734861)
43. Genovese, G. et al. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science 329, 841-845 (2010).
44. Bentley, A. R. et al. Variation in APOL1 contributes to ancestry-level differences in HDLc-kidney function association. Int. J. Nephrol. 2012, 748984 (2012).
45. Ito, K. et al. Increased burden of cardiovascular disease in carriers of APOL1 genetic variants. Circ. Res. 114, 845-850 (2014).
46. Schwartz, G. G. et al. Effects of dalcetrapib n patients with a recent acute coronary syndrome. N. Engl. J. Med. 367, 2089-2099 (2012).
47. Zhou, X. et al. Genetic deletion of low density ipoprotein receptor impairs sterol-induced mouse macrophage ABCA1 expression. A new SREBP1-dependent mechanism. J. Biol. Chem. 283, 2129-2138 (2008).
48. Medapalli, R. K., He, J. C. & Klotman, P. E. HIV-associated nephropathy: pathogenesis. Curr. Opin. Nephrol. Hypertens. 20, 306-311 (2011).
49. Kambham, N., Markowitz, G. S., Valeri, A. M., Lin, J. & D'Agati, V. D. Obesity-related glomerulopathy: an emerging epidemic. Kidney Int. 59, 1498-1509 (2001). (Pubitemid 32281241)
50. Elmaci, A. M. et al. A case of homozygous familial hypercholesterolemia with focal segmental glomerulosclerosis. Pediatr. Nephrol. 22, 1803-1805 (2007). (Pubitemid 47337441)
51. Asami, T., Ciomartan, T., Hayakawa, H., Uchiyama, M. & Tomisawa, S. Apolipoprotein Ee4 allele and nephrotic glomerular diseases in children. Pediatr. Nephrol. 13, 233-236 (1999). (Pubitemid 29204565)
52. Kopp, J. B. et al. APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy. J. Am. Soc. Nephrol. 22, 2129-2137 (2011).
53. Balasubramanyam, A. et al. Effects of transgenic expression of HIV-1 Vpr on lipid and energy metabolism in mice. Am. J. Physiol. Endocrinol. Metab. 292, E40-E48 (2007). (Pubitemid 46052923)
54. Shrivastav, S. et al. HIV-1 Vpr enhances PPAR(3/S-mediated transcription, increases PDK4 expression, and reduces PDC activity. Mol. Endocrinol. 27, 1564-1576 (2013).
55. Cui, H. L. et al. HIV-1 Nef mobilizes lipid rafts in macrophages through a pathway that competes with ABCA1-dependent cholesterol efflux. J. Lipid Res. 53, 696-708 (2012).
56. Gibellini, D. et al. HIV-related mechanisms in atherosclerosis and cardiovascular diseases. J. Cardiovasc. Med. (Hagerstown) 14, 780-790 (2013).
57. Alroy, J., Sabnis, S. & Kopp, J. B. Renal pathology in Fabry disease. J. Am. Soc. Nephrol. 13, (Suppl. 2) S134-S138 (2002). (Pubitemid 34579224)
58. Sanchez-Nino, M. D. et al. Globotriaosylsphingosine actions on human glomerular podocytes: implications for Fabry nephropathy. Nephrol. Dial. Transplant. 26, 1797-1802 (2011).
59. Thurberg, B. L. et al. Globotriaosylceramide accumulation in the Fabry kidney is cleared from multiple cell types after enzyme replacement therapy. Kidney Int. 62, 1933-1946 (2002). (Pubitemid 35366149)
60. Chander, P. N., Nurse, H. M. & Pirani, C. L. Renal involvement in adult Gaucher's disease after splenectomy. Arch. Pathol. Lab. Med. 103, 440-445 (1979). (Pubitemid 9251120)
61. Townsend, R. R., Orth, R. M., Clawson, C. M., Li, S. C. & Li, Y. T. Increased glycosphingolipid excretion associated with proteinuria. J. Clin. Invest. 62, 119-123 (1978). (Pubitemid 8367343)
62. Jin, J. et al. Soluble FLT1 binds lipid microdomains in podocytes to control cell morphology and glomerular barrier function. Cell 151, 384-399 (2012).
63. Kwak, D. H. et al. Decreases of ganglioside GM3 in streptozotocin-induced diabetic glomeruli of rats. Life Sci. 72, 1997-2006 (2003). (Pubitemid 36207536)
64. Novak, A. et al. Renal distribution of ganglioside GM3 in rat models of types 1 and 2 diabetes. J. Physiol. Biochem. 69, 727-735 (2013).
65. Galeano, B. et al. Mutation in the key enzyme of sialic acid biosynthesis causes severe glomerular proteinuria and is rescued by N-acetylmannosamine. J. Clin. Invest. 117, 1585-1594 (2007). (Pubitemid 46871343)
66. Berkovic, S. F. et al. Array-based gene discovery with three unrelated subjects shows SCARB2/LIMP-2 deficiency causes myoclonus epilepsy and glomerulosclerosis. Am. J. Hum. Genet. 82, 673-684 (2008).
67. Tatematsu, M. et al. Sandhoff disease. Acta Pathol. Jpn 31, 503-512 (1981). (Pubitemid 11000858)
68. Reivinen, J., Holthofer, H. & Miettinen, A. A cell-type specific ganglioside of glomerular podocytes in rat kidney: an O-acetylated GD3. Kidney Int. 42, 624-631 (1992).
69. Simons, M. et al. Involvement of lipid rafts in nephrin phosphorylation and organization of the glomerular slit diaphragm. Am. J. Pathol. 159, 1069-1077 (2001). (Pubitemid 32847197)
70. Holthofer, H., Reivinen, J., Solin, M. L., Haltia, A. & Miettinen, A. Decrease of glomerular disialogangliosides in puromycin nephrosis of the rat. Am. J. Pathol. 149, 1009-1015 (1996). (Pubitemid 26334184)
71. Awad, A. S. et al. Chronic sphingosine 1-phosphate 1 receptor activation attenuates early-stage diabetic nephropathy independent of lymphocytes. Kidney Int. 79, 1090-1098 (2011).
72. Jo, S. K., Bajwa, A., Awad, A.S., Lynch, K. R. & Okusa, M.D. Sphingosine-1-phosphate receptors: biology and therapeutic potential in kidney disease. Kidney Int. 73, 1220-1230 (2008). (Pubitemid 351693151)
73. Tasaki, M. et al. Rituximab treatment prevents the early development of proteinuria following pig-to-babon xeno-kidney transplantation. J. Am. Soc. Nephrol. 25, 737-744 (2014).
74. Wei, C. et al. Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis. Nat. Med. 17, 952-960 (2011).
75. Wei, C. et al. Modification of kidney barrier function by the urokinase receptor. Nat. Med. 14, 55-63 (2008).
76. Kunnen, S. & Van Eck, M. Lecithin:cholesterol acyltransferase: old friend or foe in atherosclerosis? J. Lipid Res. 53, 1783-1799 (2012).
77. Calabresi, L. & Franceschini, G. Lecithin: cholesterol acyltransferase, high-density lipoproteins, and atheroprotection in humans. Trends Cardiovasc. Med. 20, 50-53 (2010).
78. Jimi, S. et al. Possible induction of renal dysfunction in patients with lecithin:cholesterol acyltransferase deficiency by oxidized phosphatidylcholine in glomeruli. Arterioscler. Thromb. Vasc. Biol. 19, 794-801 (1999). (Pubitemid 29135186)
79. Rousset, X., Shamburek, R., Vaisman, B., Amar, M. & Remaley, A. T. Lecithin cholesterol acyltransferase: an anti-or pro-atherogenic factor? Curr. Atheroscler. Rep. 13, 249-256 (2011).
80. 2R regulates senescence through the p53 pathway. EMBO Rep. 10, 271-277 (2009).
81. 2 activity. Neural Plast. 2012, 569149 (2012).
82. Giardino, L. et al. Podocyte glutamatergic signaling contributes to the function of the glomerular filtration barrier. J. Am. Soc. Nephrol. 20, 1929-1940 (2009).
83. Collins, A. J. et al. United States Renal Data System 2011 annual data report: atlas of chronic kidney disease and end-stage renal disease in the United States. Am. J. Kidney Dis. 59, e1-e420 (2011).
84. Meyer, T. W., Bennett, P. H. & Nelson, R. G. Podocyte number predicts long-term urinary albumin excretion in Pima Indians with Type II diabetes and microalbuminuria. Diabetologia 42, 1341-1344 (1999). (Pubitemid 29500971)
85. Pagtalunan, M. E. et al. Podocyte loss and progressive glomerular injury in type II diabetes. J. Clin. Invest. 99, 342-348 (1997). (Pubitemid 27053474)
86. Steffes, M. W., Schmidt, D., McCrery, R. & Basgen, J. M. Glomerular cell number in normal subjects and in type 1 diabetic patients. Kidney Int. 59, 2104-2113 (2001). (Pubitemid 32467602)
87. Verzola, D. et al. Apoptosis in the kidneys of patients with type II diabetic nephropathy. Kidney Int. 72, 1262-1272 (2007). (Pubitemid 350059668)
88. White, K. E. et al. Podocyte number in normotensive type 1 diabetic patients with albuminuria. Diabetes 51, 3083-3089 (2002).
89. Hovind, P. et al. Decreasing incidence of severe diabetic microangiopathy in type 1 diabetes. Diabetes Care 26, 1258-1264 (2003). (Pubitemid 36929282)
90. Gaede, P., Lund-Andersen, H., Parving, H. H. & Pedersen, O. Effect of a multifactorial intervention on mortality in type 2 diabetes. N. Engl. J. Med. 358, 580-591 (2008). (Pubitemid 351214285)
91. Miller, Y. I., Choi, S. H., Fang, L. & Harkewicz, R. Toll-like receptor-4 and lipoprotein accumulation in macrophages. Trends Cardiovasc. Med. 19, 227-232 (2009).
92. Shi, H. et al. TLR4 links innate immunity and fatty acid-induced insulin resistance. J. Clin. Invest. 116, 3015-3025 (2006). (Pubitemid 44684486)
93. Qi, M., Liu, Y., Freeman, M.R. & Solomon, K.R. Cholesterol-regulated stress fiber reduction. J. Cell Biochem. 106, 1031-1040 (2009).
94. Yu, B.L. Zhao, S.P. & Hu, J.R. Cholesterol imbalance in adipocytes: a possible mechanism of adipocytes dysfunction in obesity. Obes. Rev. 11, 560-567 (2010).
95. Jiang, T. et al. Diet-induced obesity in C57BL/56J 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)
96. Wang, Z. et al. Regulation of renal lipid metabolism, lipid accumulation, and glomerulosclerosis in FVBdb/db mice with type 2 diabetes. Diabetes 54, 2328-2335 (2005). (Pubitemid 41134259)
97. Nosadini, R. & Tonolo, G. Role of oxidized low density lipoproteins and free fatty acids in the pathogenesis of glomerulopathy and tubulointerstitial lesions in type 2 diabetes. Nutr. Metab. Cardiovasc. Dis. 21, 79-85 (2011).
98. Tam, J. et al. Peripheral cannabinoid-1 receptor inverse agonism reduces obesity by reversing leptin resistance. Cell. Metab. 16, 167-179 (2012).
99. Saltiel, A. R. & Kahn, C. R. Insulin signalling and the regulation of glucose and lipid metabolism. Nature 414, 799-806 (2001). (Pubitemid 34000783)
100. Saltiel, A. R. & Pessin, J. E. Insulin signaling in microdomains of the plasma membrane. Traffic 4, 711-716 (2003). (Pubitemid 37361852)
101. Simons, K. & Ikonen, E. Functional rafts in cell membranes. Nature 387, 569-572 (1997). (Pubitemid 27248754)
102. Uhles, S., Moede, T., Leibiger, B., Berggren, P. O. & Leibiger, I. B. Isoform-specific insulin receptor signaling involves different plasma membrane domains. J. Cell Biol. 163, 1327-1337 (2003). (Pubitemid 38032093)
103. White, M. F. & Kahn, C. R. The insulin signaling system. J. Biol. Chem. 269, 1-4 (1994). (Pubitemid 24026607)
104. Ekstrand, A. V., Groop, P. H. & Gronhagen-Riska, C. Insulin resistance precedes microalbuminuria in patients with nsulin-dependent diabetes mellitus. Nephrol. Dial. Transplant. 13, 3079-3083 (1998). (Pubitemid 28534711)
105. Yip, J. et al. Insulin resistance in insulin-dependent diabetic patients with microalbuminuria. Lancet 342, 883-887 (1993). (Pubitemid 23291590)
106. Groop, L. et al. Insulin resistance, hypertension and microalbuminuria in patients with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 36, 642-647 (1993). (Pubitemid 23186457)
107. Parvanova, A. I. et al. Insulin resistance and microalbuminuria: a cross-sectional, case-control study of 158 patients with type 2 diabetes and different degrees of urinary albumin excretion. Diabetes 55, 1456-1462 (2006). (Pubitemid 44195387)
108. Forsblom, C. M. et al. Insulin resistance and abnormal albumin excretion in non-diabetic first-degree relatives of patients with NIDDM. Diabetologia 38, 363-369 (1995).
109. Yip, J., Mattock, M., Sethi, M., Morocutti, A. & Viberti, G. Insulin resistance in family members of insulin-dependent diabetic patients with microalbuminuria. Lancet 341, 369-370 (1993). (Pubitemid 23039720)
110. Mykkanen, L. et al. Microalbuminuria is associated with insulin resistance in nondiabetic subjects: the insulin resistance atherosclerosis study. Diabetes 47, 793-800 (1998). (Pubitemid 28201810)
111. Willer, C. J. et al. Newly identified loci that nfluence lipid concentrations and risk of coronary artery disease. Nat. Genet. 40, 161-169 (2008). (Pubitemid 351171403)
112. Zhou, H., Tan, K. C., Shiu, S. W. & Wong, Y Cellular cholesterol efflux to serum is impaired n diabetic nephropathy. Diabetes Metab. Res. Rev. 24, 617-623 (2008).
113. Fang, L. et al. Control of angiogenesis by AIBP-mediated cholesterol efflux. Nature 498, 118-122 (2013).
114. Gohda, T. et al. Circulating TNF receptors 1 and 2 predict stage 3 CKD in type 1 diabetes. J. Am. Soc. Nephrol. 23, 516-524 (2012).
115. Niewczas, M. A. et al. Circulating TNF receptors 1 and 2 predict ESRD in type 2 diabetes. J. Am. Soc. Nephrol. 23, 507-515 (2012).
116. Chen, Y et al. Inflammatory stress exacerbates hepatic cholesterol accumulation via disrupting cellular cholesterol export. J. Gastroenterol. Hepatol. 27, 974-984 (2012).
117. Field, F J., Watt, K. & Mathur, S. N. TNF-a decreases ABCA1 expression and attenuates HDL cholesterol efflux in the human intestinal cell line Caco-2. J. Lipid Res. 51, 1407-1415 (2010).
118. Hashizume, M. & Mihara, M. Atherogenic effects of TNF-a and IL-6 via up-regulation of scavenger receptors. Cytokine 58, 424-430 (2012).
119. Kramer-Guth, A. et al. Uptake and metabolism of ipoproteins from patients with diabetes mellitus type II by glomerular epithelial cells. Nephrol. Dial. Transplant. 12, 1336-1343 (1997). (Pubitemid 27353021)
120. Gutwein, P. et al. CXCL16 is expressed in podocytes and acts as a scavenger receptor for oxidized low-density lipoprotein. Am. J. Pathol. 174, 2061-2072 (2009).
121. Bussolati, B. et al. Statins prevent oxidized LDL-induced injury of glomerular podocytes by activating the phosphatidylinositol 3-kinase/AKT- signaling pathway. J. Am. Soc. Nephrol. 16, 1936-1947 (2005). (Pubitemid 41716424)
122. Hyvonen, M. E. et al. Lipid phosphatase SHIP2 downregulates insulin signalling in podocytes. Mol. Cell Endocrinol. 328, 70-79 (2010).
123. Lennon, R. et al. Saturated fatty acids induce insulin resistance in human podocytes: implications for diabetic nephropathy. Nephrol. Dial. Transplant. 24, 3288-3296 (2009).
124. Sieber, J. et al. Regulation of podocyte survival and endoplasmic reticulum stress by fatty acids. Am. J. Physiol. Renal Physiol. 299, F821-F829 (2010).
125. Sieber, J. et al. Susceptibility of podocytes to palmitic acid is regulated by stearoyl-CoA desaturases 1 and 2. Am. J. Pathol. 183, 735-744 (2013).
126. Nosadini, R. & Tonolo, G. Role of oxidized low density lipoproteins and free fatty acids in the pathogenesis of glomerulopathy and tubulointerstitial lesions in type 2 diabetes. Nutr. Metab. Cardiovasc. Dis. 21, 79-85 (2011).
127. Soetikno, V. et al. Curcumin decreases renal triglyceride accumulation through AMPK-SREBP signaling pathway in streptozotocin-induced type 1 diabetic rats. J. Nutr. Biochem. 24, 796-802 (2013)
128. Lee, H. S. Mechanisms and consequences of hypertriglyceridemia and cellular lipid accumulation in chronic kidney disease and metabolic syndrome. Histol. Histopathol. 26, 1599-1610 (2011).
129. Chen, H. M., Zhen, C. X., Gao, Q., Ge, Y. C. & Liu, Z. H. Heart-type fatty acid binding protein is associated with proteinuria in obesity. PLoS ONE. 7, e45691 (2011).
130. Lee, H. S. & Lee, S. K. Intraglomerular lipid deposition in renal disease. Miner. Electrolyte Metab. 19, 144-148 (1993).
131. Douglas, K., O'Malley, P. G. & Jackson, J. L. Meta-analysis: the effect of statins on albuminuria. Ann. Intern. Med. 145, 117-124 (2006). (Pubitemid 46780585)
132. Agarwal, R. Effects of statins on renal function. Am. J. Cardiol. 97, 748-755 (2006). (Pubitemid 43255052)
133. Colhoun, H. M. et al. Effects of atorvastatin on kidney outcomes and cardiovascular disease in patients with diabetes: an analysis from the Collaborative Atorvastatin Diabetes Study (CARDS). Am. J. Kidney Dis. 54, 810-819 (2009).
134. Katz, A. et al. Safety, pharmacokinetics, and pharmacodynamics of single doses of LXR-623, a novel liver X-receptor agonist, in healthy participants. J. Clin. Pharmacol. 49, 643-649 (2009).
135. Grefhorst, A. et al. Stimulation of lipogenesis by pharmacological activation of the liver X receptor leads to production of large, triglyceride-rich very low density lipoprotein particles. J. Biol. Chem. 277, 34182-34190 (2002).
136. Stella, V. J. & He, Q. Cyclodextrins. Toxicol. Pathol. 36, 30-42 (2008).
137. Arima, H. et al. Inhibitory effects of dimethylacetyl-beta-cyclodextrin on lipopolysaccharide-induced macrophage activation and endotoxin shock in mice. Biochem. Pharmacol. 70, 1506-1517 (2005). (Pubitemid 41483461)
138. Liu, P. et al. Sphingomyelinase activates GLUT4 translocation via a cholesterol-dependent mechanism. Am. J. Physiol. Cell Physiol. 286, C317-C329 (2004). (Pubitemid 38146355)
139. Horvath, E. M., Tackett, L. & Elmendorf, J. S. A novel membrane-based anti-diabetic action of atorvastatin. Biochem. Biophys. Res. Commun. 372, 639-643 (2008).
140. Horvath, E. M. et al. Antidiabetogenic effects of chromium mitigate hyperinsulinemia-induced cellular insulin resistance via correction of plasma membrane cholesterol imbalance. Mol. Endocrinol. 22, 937-950 (2008) (Pubitemid 351482829)
141. Addi and Cassi Fund. addiandcassi.com [online], http://addiandcassi.com/ walgreens-support-twins-niemann-pick-type-receive-cyclodextrin-treatments-home/ (2014).
142. Keech, A. et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet 366, 1849-1861 (2005).
143. Wang, X. X. et al. The farnesoid X receptor modulates renal lipid metabolism and diet-induced renal inflammation, fibrosis, and proteinuria. Am. J. Physiol. Renal Physiol. 297, F1587-F1596 (2009).
144. US National Library of Medicine. ClinicalTrials.gov [online] http://clinicaltrials.gov/ct2/show/NCT01782027?term=Tangier&rank=1 (2013).