Sphingolipids in High Fat Diet and Obesity-Related Diseases

Mediators of Inflammation

Volumn 2015, Issue , 2015, Pages

  Choi, Songhwa ^a,b   Snider, Ashley J ^a,b,c  

^a STONY BROOK UNIVERSITY   (United States)

^b Stony Brook Medicine   (United States)

^c VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5 AMINO 4 IMIDAZOLECARBOXAMIDE RIBOSIDE; CANNABINOID 1 RECEPTOR; CD36 ANTIGEN; CERAMIDE; ENDOTHELIAL NITRIC OXIDE SYNTHASE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; SPHINGOLIPID; SPHINGOMYELIN; SPHINGOSINE; SPHINGOSINE 1 PHOSPHATE; TOLL LIKE RECEPTOR 4; TUMOR NECROSIS FACTOR ALPHA;

ADIPOSE TISSUE; CARDIOVASCULAR SYSTEM; CARDIOVASCULAR TISSUE; ENDOTHELIAL DYSFUNCTION; HUMAN; INSULIN RESISTANCE; LIPID DIET; LIVER; NONALCOHOLIC FATTY LIVER; NONHUMAN; OBESITY; PLASMA; PRIORITY JOURNAL; REVIEW; SKELETAL MUSCLE; SPHINGOLIPID METABOLISM; COMPLICATION; METABOLISM; PHYSIOLOGY;

ADIPOSE TISSUE; CARDIOVASCULAR SYSTEM; DIET, HIGH-FAT; HUMANS; INSULIN RESISTANCE; LIVER; MUSCLE, SKELETAL; OBESITY; SPHINGOLIPIDS;

EID: 84948823032     PISSN: 09629351     EISSN: 14661861     Source Type: Journal    
DOI: 10.1155/2015/520618     Document Type: Review

References (98)

1. C. L. Ogden, M. D. Carroll, B. K. Kit, and K. M. Flegal, Prevalence of childhood and adult obesity in the United States, 2011-2012, The Journal of the American Medical Association, vol. 311, no. 8, pp. 806-814, 2014.
2. Y. A. Hannun and L. M. Obeid, Principles of bioactive lipid signalling: lessons from sphingolipids, Nature Reviews Molecular Cell Biology, vol. 9, no. 2, pp. 139-150, 2008.
3. A. J. Snider, K. A. Orr Gandy, and L. M. Obeid, Sphingosine kinase: role in regulation of bioactive sphingolipidmediators in inflammation, Biochimie, vol. 92, no. 6, pp. 707-715, 2010.
4. T. Hornemann, A. Penno, M. F. Rtti et al., The SPTLC3 subunit of serine palmitoyltransferase generates short chain sphingoid bases, Journal of Biological Chemistry, vol. 284, no. 39, pp. 26322-26330, 2009.
5. S. A. Summers, Ceramides in insulin resistance and lipotoxicity, Progress in Lipid Research, vol. 45, no. 1, pp. 42-72, 2006.
6. M. Levy and A. H. Futerman, Mammalian ceramide synthases, IUBMB Life, vol. 62, no. 5, pp. 347-356, 2010.
7. J. T. Brozinick, E. Hawkins, H. Hoang Bui et al., Plasma sphingolipids are biomarkers of metabolic syndrome in non-human primates maintained on a Western-style diet, International Journal of Obesity, vol. 37, no. 8, pp. 1064-1070, 2013.
8. C. R. Bruce, S. Risis, J. R. Babb et al., Overexpression of sphingosine kinase 1 prevents ceramide accumulation and amelioratesmuscle insulin resistance in high-fat diet-fed mice, Diabetes, vol. 61, no. 12, pp. 3148-3155, 2012.
9. R. Cinar, G. Godlewski, J. Liu et al., Hepatic cannabinoid-1 receptors mediate diet-induced insulin resistance by increasing de novo synthesis of long-chain ceramides, Hepatology, vol. 59, no. 1, pp. 143-153, 2014.
10. A. B. Thrush, D. N. Brindley, A. Chabowski, G. J. Heigenhauser, and D. J. Dyck, Skeletal muscle lipogenic protein expression is not different between lean and obese individuals: a potential factor in ceramide accumulation, Journal of Clinical Endocrinology and Metabolism, vol. 94, no. 12, pp. 5053-5061, 2009.
11. N. Turner, G.M. Kowalski, S. J. Leslie et al., Distinct patterns of tissue-specific lipid accumulation during the induction of insulin resistance in mice by high-fat feeding, Diabetologia, vol. 56, no. 7, pp. 1638-1648, 2013.
12. B. T. Bikman, Y. Guan, G. Shui et al., Fenretinide prevents lipidinduced insulin resistance by blocking ceramide biosynthesis, The Journal of Biological Chemistry, vol. 287, no. 21, pp. 17426-17437, 2012.
13. I. R. Lanza, A. Blachnio-Zabielska, M. L. Johnson et al., Influence of fish oil on skeletal muscle mitochondrial energetics and lipid metabolites during high-fat diet, American Journal of Physiology-Endocrinology andMetabolism, vol. 304, no. 12, pp. E1391-E1403, 2013.
14. W. Hu, J. Bielawski, F. Samad, A. H. Merrill Jr., and L. A. Cowart, Palmitate increases sphingosine-1-phosphate in C2C12 myotubes via upregulation of sphingosine kinase message and activity, Journal of Lipid Research, vol. 50, no. 9, pp. 1852-1862, 2009.
15. M. Park, D. Wu, T. Park et al., APPL1 transgenicmice are protected from high-fat diet-induced cardiac dysfunction, American Journal of Physiology-Endocrinology and Metabolism, vol. 305, no. 7, pp. E795-E804, 2013.
16. C. Shah, G. Yang, I. Lee, J. Bielawski, Y. A. Hannun, and F. Samad, Protection from high fat diet-induced increase in ceramide in mice lacking plasminogen activator inhibitor 1, The Journal of Biological Chemistry, vol. 283, no. 20, pp. 13538-13548, 2008.
17. S. M. Turpin, H. T. Nicholls, D. M. Willmes et al., Obesityinduced CerS6-dependent C16:0 ceramide production promotes weight gain and glucose intolerance, Cell Metabolism, vol. 20, no. 4, pp. 678-686, 2014.
18. J. Abildgaard, D. C. Henstridge, A. T. Pedersen et al., In vitro palmitate treatment ofmyotubes frompostmenopausal women leads to ceramide accumulation, inflammation and affected insulin signaling, PLoS ONE, vol. 9, no. 7, Article ID e101555, 2014.
19. A.-C. Aurich, B. Niemann, R. Pan et al., Age-dependent effects of high fat-diet onmurine left ventricles: role of palmitate, Basic Research in Cardiology, vol. 108, no. 5, article 369, 2013.
20. M. M. Y. Sung, D. P. Y. Koonen, C.-L.M. Soltys, R. L. Jacobs, M. Febbraio, and J. R. B. Dyck, Increased CD36 expression in middle-aged mice contributes to obesity-related cardiac hypertrophy in the absence of cardiac dysfunction, Journal of Molecular Medicine, vol. 89, no. 5, pp. 459-469, 2011.
21. N. Tardif, J. Salles, C. Guillet et al., Muscle ectopic fat deposition contributes to anabolic resistance in obese sarcopenic old rats through eIF2 activation, Aging Cell, vol. 13, no. 6, pp. 1001-1011, 2014.
22. M. J. Watt, A. C. Barnett, C. R. Bruce, S. Schenk, J. F. Horowitz, and A. J. Hoy, Regulation of plasma ceramide levels with fatty acid oversupply: evidence that the liver detects and secretes de novo synthesised ceramide, Diabetologia, vol. 55, no. 10, pp. 2741-2746, 2012.
23. K.A. Erickson, M. E. Smith, T. S. Anthonymuthu et al., AICAR inhibits ceramide biosynthesis in skeletal muscle, Diabetology & Metabolic Syndrome, vol. 4, no. 1, article 45, 2012.
24. L. Longato, M. Tong, J. R. Wands, and S. M. de laMonte, High fat diet induced hepatic steatosis and insulin resistance: role of dysregulated ceramide metabolism, Hepatology Research, vol. 42, no. 4, pp. 412-427, 2012.
25. S. B. Russo, R. Tidhar, A. H. Futerman, and L. A. Cowart, Myristate-derived d16:0 sphingolipids constitute a cardiac sphingolipid pool with distinct synthetic routes and functional properties, The Journal of Biological Chemistry, vol. 288, no. 19, pp. 13397-13409, 2013.
26. A. Blachnio-Zabielska, M. Baranowski, P. Zabielski, and J. Gorski, Effect of high fat diet enriched with unsaturated and diet rich in saturated fatty acids on sphingolipid metabolism in rat skeletalmuscle, Journal of Cellular Physiology, vol. 225, no. 3, pp. 786-791, 2010.
27. H. Shi, M. V. Kokoeva, K. Inouye, I. Tzameli, H. Yin, and J. S. Flier, TLR4 links innate immunity and fatty acid-induced insulin resistance, The Journal of Clinical Investigation, vol. 116, no. 11, pp. 3015-3025, 2006.
28. W. L. Holland, B. T. Bikman, L.-P. Wang et al., Lipid-induced insulin resistance mediated by the proinflammatory receptor TLR4 requires saturated fatty acid-induced ceramide biosynthesis in mice, Journal of Clinical Investigation, vol. 121, no. 5, pp. 1858-1870, 2011.
29. G. Chocian, A. Chabowski, M. Zendzian-Piotrowska, E. Harasim, B. Lukaszuk, and J.Gorski, High fat diet induces ceramide and sphingomyelin formation in rats liver nuclei, Molecular and Cellular Biochemistry, vol. 340, no. 1-2, pp. 125-131, 2010.
30. K.M. Boini, C. Zhang, M. Xia, J. L. Poklis, and P.-L. Li, Role of sphingolipid mediator ceramide in obesity and renal injury in mice fed a high-fat diet, Journal of Pharmacology and Experimental Therapeutics, vol. 334, no. 3, pp. 839-846, 2010.
31. D. A. Brown and E. London, Structure and function of sphingolipid-and cholesterol-richmembrane rafts, TheJournal of Biological Chemistry, vol. 275, no. 23, pp. 17221-17224, 2000.
32. X.-C. Jiang, F. Paultre, T. A. Pearson et al., Plasma sphingomyelin level as a risk factor for coronary artery disease, Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 20, no. 12, pp. 2614-2618, 2000.
33. K. Eisinger, G. Liebisch, G. Schmitz, C. Aslanidis, S. Krautbauer, and C. Buechler, Lipidomic analysis of serum from high fat diet induced obese mice, International Journal of Molecular Sciences, vol. 15, no. 2, pp. 2991-3002, 2014.
34. J. Jin, X. Zhang, Z. Lu et al., Acid sphingomyelinase plays a key role in palmitic acid-amplified inflammatory signaling triggered by lipopolysaccharide at low concentrations in macrophages, American Journal of Physiology: Endocrinology and Metabolism, vol. 305, no. 7, pp. E853-E867, 2013.
35. J. Liu, H. Zhang, Z. Li et al., Sphingomyelin synthase 2 is one of the determinants for plasma and liver sphingomyelin levels in mice, Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 29, no. 6, pp. 850-856, 2009.
36. O. Cuvillier, L. Edsall, and S. Spiegel, Involvement of sphingosine in mitochondria-dependent Fas-induced apoptosis of type II Jurkat T cells, The Journal of Biological Chemistry, vol. 275, no. 21, pp. 15691-15700, 2000.
37. K. Kagedal, M. Zhao, I. Svensson, and U. T. Brunk, Sphingosine-induced apoptosis is dependent on lysosomal proteases, Biochemical Journal, vol. 359, no. 2, pp. 335-343, 2001.
38. H. Okuwa, T. Kanno, Y. Fujita et al., Sphingosine suppresses mesothelioma cell proliferation by inhibiting PKC- and inducing cell cycle arrest at the G0/G1 phase, Cellular Physiology and Biochemistry, vol. 30, no. 4, pp. 995-1004, 2012.
39. M. J. Dekker, C. Baker, M. Naples et al., Inhibition of sphingolipid synthesis improves dyslipidemia in the diet-induced hamster model of insulin resistance: evidence for the role of sphingosine and sphinganine in hepatic VLDL-apoB100 overproduction, Atherosclerosis, vol. 228, no. 1, pp. 98-109, 2013.
40. K. Kurek, D. M. Piotrowska, P. Wiesiolek-Kurek et al., Inhibition of ceramide de novo synthesis reduces liver lipid accumulation in rats with nonalcoholic fatty liver disease, Liver International, vol. 34, no. 7, pp. 1074-1083, 2014.
41. Y. Liu, S. Turdi, T. Park et al., Adiponectin corrects high-fat diet-induced disturbances in muscle metabolomic profile and whole-body glucose homeostasis, Diabetes, vol. 62, no. 3, pp. 743-752, 2013.
42. G.M. Kowalski, A. L. Carey, A. Selathurai, B. A. Kingwell, and C. R. Bruce, Plasma sphingosine-1-phosphate is elevated in obesity, PLoS ONE, vol. 8, no. 9, Article ID e72449, 2013.
43. S. Fayyaz, J. Henkel, L. Japtok et al., Involvement of sphingosine 1-phosphate in palmitate-induced insulin resistance of hepatocytes via the S1P2 receptor subtype, Diabetologia, vol. 57, no. 2, pp. 373-382, 2014.
44. L. Japtok, E. I. Schmitz, S. Fayyaz, S. Krmer, L. Hsu, and B. Kleuser, Sphingosine 1-phosphate counteracts insulin signaling in pancreatic beta-cells via the sphingosine 1-phosphate receptor subtype 2, The FASEB Journal, vol. 29, no. 8, pp. 3357-3369, 2015.
45. N. Igarashi, T. Okada, S. Hayashi, T. Fujita, S. Jahangeer, and S.-I. Nakamura, Sphingosine kinase 2 is a nuclear protein and inhibits DNA synthesis, Journal of Biological Chemistry, vol. 278, no. 47, pp. 46832-46839, 2003.
46. K. R. Johnson, K. P. Becker, M. M. Facchinetti, Y. A. Hannun, and L. M. Obeid, PKC-dependent activation of sphingosine kinase 1 and translocation to the plasma membrane: extracellular release of sphingosine-1-phosphate induced by phorbol 12-myristate 13-acetate (PMA), The Journal of Biological Chemistry, vol. 277, no. 38, pp. 35257-35262, 2002.
47. W.-Q. Lai, A.W. Irwan, H.H. Goh, A. J. Melendez, I.B. McInnes, and B. P. Leung, Distinct roles of sphingosine kinase 1 and 2 in murine collagen-induced arthritis, The Journal of Immunology, vol. 183, no. 3, pp. 2097-2103, 2009.
48. J. S. Ross, W. Hu, B. Rosen, A. J. Snider, L. M. Obeid, and L. A. Cowart, Sphingosine kinase 1 is regulated by peroxisome proliferator-activated receptor in response to free fatty acids and is essential for skeletal muscle interleukin-6 production and signaling in diet-induced obesity, The Journal of Biological Chemistry, vol. 288, no. 31, pp. 22193-22206, 2013.
49. M. Nagahashi, K. Takabe, R. Liu et al., Conjugated bile acidactivated S1P receptor 2 is a key regulator of sphingosine kinase 2 and hepatic gene expression, Hepatology, vol. 61, no. 4, pp. 1216-1226, 2015.
50. A. R. Saltiel and C. R. Kahn, Insulin signalling and the regulation of glucose and lipidmetabolism, Nature, vol. 414, no. 6865, pp. 799-806, 2001.
51. E. L. Whiteman, H. Cho, and M. J. Birnbaum, Role of Akt/protein kinase B in metabolism, Trends in Endocrinology and Metabolism, vol. 13, no. 10, pp. 444-451, 2002.
52. G. Yang, L. Badeanlou, J. Bielawski, A. J. Roberts, Y. A. Hannun, and F. Samad, Central role of ceramide biosynthesis in body weight regulation, energy metabolism, and the metabolic syndrome, American Journal of Physiology: Endocrinology and Metabolism, vol. 297, no. 1, pp. E211-E224, 2009.
53. S. Mitsutake, K. Zama, H. Yokota et al., Dynamic modification of sphingomyelin in lipid microdomains controls development of obesity, fatty liver, and type 2 diabetes, Journal of Biological Chemistry, vol. 286, no. 32, pp. 28544-28555, 2011.
54. Z. Li, H. Zhang, J. Liu et al., Reducing plasma membrane sphingomyelin increases insulin sensitivity, Molecular and Cellular Biology, vol. 31, no. 20, pp. 4205-4218, 2011.
55. S. Raichur, S. T. Wang, P. W. Chan et al., CerS2 haploinsufficiency inhibits -oxidation and confers susceptibility to dietinduced steatohepatitis and insulin resistance, CellMetabolism, vol. 20, no. 4, pp. 687-695, 2014.
56. S.Y. Lee, I. Hong, B. Kim et al., Activation of sphingosine kinase 2 by endoplasmic reticulum stress ameliorates hepatic steatosis and insulin resistance in mice, Hepatology, vol. 62, no. 1, pp. 135-146, 2015.
57. P. Angulo, Medical progress: nonalcoholic fatty liver disease, The New England Journal of Medicine, vol. 346, no. 16, pp. 1221-1231, 2002.
58. K. Begriche, A. Igoudjil, D. Pessayre, and B. Fromenty, Mitochondrial dysfunction in NASH: causes, consequences and possible means to prevent it, Mitochondrion, vol. 6, no. 1, pp. 1-28, 2006.
59. J. D. Browning and J. D. Horton, Molecular mediators of hepatic steatosis and liver injury, The Journal of Clinical Investigation, vol. 114, no. 2, pp. 147-152, 2004.
60. J. Y. Xia, W. L. Holland, C. M. Kusminski et al., Targeted induction of ceramide degradation leads to improved systemic metabolism and reduced hepatic steatosis, CellMetabolism, vol. 22, no. 2, pp. 266-278, 2015.
61. U. Ozcan, Q. Cao, E. Yilmaz et al., Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes, Science, vol. 306, no. 5695, pp. 457-461, 2004.
62. J.-S. Lee, R. Mendez, H. H. Heng, Z.-Q. Yang, and K. Zhang, Pharmacological ER stress promotes hepatic lipogenesis and lipid droplet formation, American Journal of Translational Research, vol. 4, no. 1, pp. 102-113, 2012.
63. R. Fucho, L. Martiez, A. Baulies et al., ASMase regulates autophagy and lysosomal membrane permeabilization and its inhibition prevents early stage non-alcoholic steatohepatitis, Journal of Hepatology, vol. 61, no. 5, pp. 1126-1134, 2014.
64. G. Kewalramani, P. J. Bilan, and A. Klip, Muscle insulin resistance: assault by lipids, cytokines and local macrophages, Current Opinion in Clinical Nutrition and Metabolic Care, vol. 13, no. 4, pp. 382-390, 2010.
65. J. A. Chavez, M. M. Siddique, S. T. Wang, J. Ching, J. A. Shayman, and S. A. Summers, Ceramides and glucosylceramides are independent antagonists of insulin signaling, Journal of Biological Chemistry, vol. 289, no. 2, pp. 723-734, 2014.
66. D. J. Powell, S. Turban, A. Gray, E. Hajduch, and H. S. Hundal, Intracellular ceramide synthesis and protein kinase C activation play an essential role in palmitate-induced insulin resistance in rat L6 skeletal muscle cells, Biochemical Journal, vol. 382, part 2, pp. 619-629, 2004.
67. M. K. Verma, A. N. Yateesh, K. Neelima et al., Inhibition of neutral sphingomyelinases in skeletal muscle attenuates fattyacid induced defects in metabolism and stress, SpringerPlus, vol. 3, article 255, 2014.
68. C. R. Bruce, S. Risis, J. R. Babb et al., The sphingosine-1-phosphate analog FTY720 reduces muscle ceramide content and improves glucose tolerance in high fat-fed male mice, Endocrinology, vol. 154, no. 1, pp. 65-76, 2013.
69. B. K. Pedersen and M. A. Febbraio, Muscle as an endocrine organ: focus on muscle-derived interleukin-6, Physiological Reviews, vol. 88, no. 4, pp. 1379-1406, 2008.
70. A. Steensberg, G. Van Hall, T. Osada, M. Sacchetti, B. Saltin, and B. K. Pedersen, Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6, Journal of Physiology, vol. 529, no. 1, pp. 237-242, 2000.
71. G. S. Hotamisligil, N. S. Shargill, and B. M. Spiegelman, Adipose expression of tumor necrosis factor: direct role in obesity-linked insulin resistance, Science, vol. 259, no. 5091, pp. 87-91, 1993.
72. A. H. Berg and P. E. Scherer, Adipose tissue, inflammation, and cardiovascular disease, Circulation Research, vol. 96, no. 9, pp. 939-949, 2005.
73. N. Ouchi, J. L. Parker, J. J. Lugus, and K. Walsh, Adipokines in inflammation andmetabolic disease, Nature Reviews Immunology, vol. 11, no. 2, pp. 85-97, 2011.
74. Y. Zhang, R. Proenca, M. Maffei, M. Barone, L. Leopold, and J. M. Friedman, Positional cloning of the mouse obese gene and its human homologue, Nature, vol. 372, no. 6505, pp. 425-432, 1994.
75. I. Shimomura, T. Funahashi, M. Takahashi et al., Enhanced expression of PAI-1 in visceral fat: possible contributor to vascular disease in obesity, Nature Medicine, vol. 2, no. 7, pp. 800-803, 1996.
76. E. Hu, P. Liang, and B. M. Spiegelman, AdipoQ is a novel adipose-specific gene dysregulated in obesity, Journal of Biological Chemistry, vol. 271, no. 18, pp. 10697-10703, 1996.
77. N. Barbarroja, S. Rodriguez-Cuenca, H. Nygren et al., Increased dihydroceramide/ceramide ratio mediated by defective expression of degs1 impairs adipocyte differentiation and function, Diabetes, vol. 64, no. 4, pp. 1180-1192, 2015.
78. S. Mitsutake, T. Date, H. Yokota, M. Sugiura, T. Kohama, and Y. Igarashi, Ceramide kinase deficiency improves diet-induced obesity and insulin resistance, FEBS Letters, vol. 586, no. 9, pp. 1300-1305, 2012.
79. A. Kihara and Y. Igarashi, Production and release of sphingosine 1-phosphate and the phosphorylated form of the immunomodulator FTY720, Biochimica et BiophysicaActa, vol. 1781, no. 9, pp. 496-502, 2008.
80. K. Takabe, S. W. Paugh, S. Milstien, and S. Spiegel, Inside-out signaling of sphingosine-1-phosphate: therapeutic targets, Pharmacological Reviews, vol. 60, no. 2, pp. 181-195, 2008.
81. M. R. Kendall and C. J. Hupfeld, FTY720, a sphingosine-1-phosphate receptor modulator, reverses high-fat diet-induced weight gain, insulin resistance and adipose tissue inflammation in C57BL/6 mice, Diabetes, Obesity andMetabolism, vol. 10, no. 9, pp. 802-805, 2008.
82. M.-H. Moon, J.-K. Jeong, J.-H. Lee et al., Antiobesity activity of a sphingosine 1-phosphate analogue FTY720 observed in adipocytes and obese mouse model, Experimental and Molecular Medicine, vol. 44, no. 10, pp. 603-614, 2012.
83. T. Hashimoto, J. Igarashi, and H. Kosaka, Sphingosine kinase is induced in mouse 3T3-L1 cells and promotes adipogenesis, Journal of Lipid Research, vol. 50, no. 4, pp. 602-610, 2009.
84. L. F. Van Gaal, I. L. Mertens, and C. E. De Block, Mechanisms linking obesity with cardiovascular disease, Nature, vol. 444, no. 7121, pp. 875-880, 2006.
85. J. E. Deanfield, J. P. Halcox, and T. J. Rabelink, Endothelial function and dysfunction: testing and clinical relevance, Circulation, vol. 115, no. 10, pp. 1285-1295, 2007.
86. M. Chakraborty, C. Lou, C. Huan et al., Myeloid cell-specific serine palmitoyltransferase subunit 2 haploinsufficiency reducesmurine atherosclerosis, Journal of Clinical Investigation, vol. 123, no. 4, pp. 1784-1797, 2013.
87. T.-S. Park, R. L. Panek, S. B. Mueller et al., Inhibition of sphingomyelin synthesis reduces atherogenesis in apolipoprotein E-knockout mice, Circulation, vol. 110, no. 22, pp. 3465-3471, 2004.
88. Q.-J. Zhang, W. L. Holland, L. Wilson et al., Ceramide mediates vascular dysfunction in diet-induced obesity by PP2Amediated dephosphorylation of the eNOS-Akt complex, Diabetes, vol. 61, no. 7, pp. 1848-1859, 2012.
89. V. C. Mehra, E. Jackson, X. M. Zhang et al., Ceramideactivated phosphatase mediates fatty acid-induced endothelial VEGF resistance and impaired angiogenesis, American Journal of Pathology, vol. 184, no. 5, pp. 1562-1576, 2014.
90. S. L. Schissel, J. Tweedie-Hardman, J. H. Rapp, G. Graham, K. J. Williams, and I. Tabas, Rabbit aorta and human atherosclerotic lesions hydrolyze the sphingomyelin of retained low-density lipoprotein. Proposed role for arterial-wall sphingomyelinase in subendothelial retention and aggregation of atherogenic lipoproteins, Journal of Clinical Investigation, vol. 98, no. 6, pp. 1455-1464, 1996.
91. Y.-R. Zhao, J.-B. Dong, Y. Li, and M.-P. Wu, Sphingomyelin synthase 2 over-expression induces expression of aortic inflammatory biomarkers and decreases circulating EPCs in ApoE KO mice, Life Sciences, vol. 90, no. 21-22, pp. 867-873, 2012.
92. M.R. Hojjati, Z. Li, H. Zhou et al., Effect ofmyriocinonplasma sphingolipid metabolism and atherosclerosis in apoE-deficient mice, Journal of Biological Chemistry, vol. 280, no. 11, pp. 10284-10289, 2005.
93. E. N. Glaros, W. S. Kim, B. J. Wu et al., Inhibition of atherosclerosis by the serine palmitoyl transferase inhibitor myriocin is associated with reduced plasma glycosphingolipid concentration, Biochemical Pharmacology, vol. 73, no. 9, pp. 1340-1346, 2007.
94. B. Garner, H. R. Mellor, T. D. Butters, R. A. Dwek, and F. M. Platt, Modulation of THP-1 macrophage and cholesterolloaded foamcell apolipoprotein E levels by glycosphingolipids, Biochemical and Biophysical Research Communications, vol. 290, no. 5, pp. 1361-1367, 2002.
95. N. Gong, H. Wei, S. H. Chowdhury, and S. Chatterjee, Lactosylceramide recruits PKC/ and phospholipase A2 to stimulate PECAM-1 expression in human monocytes and adhesion to endothelial cells, Proceedings of the National Academy of Sciences of theUnited States of America, vol. 101, no. 17, pp. 6490-6495, 2004.
96. S. Chatterjee, D. Bedja, S. Mishra et al., Inhibition of glycosphingolipid synthesis ameliorates atherosclerosis and arterial stiffness in apolipoprotein E-/- mice and rabbits fed a high-fat and -cholesterol diet, Circulation, vol. 129, no. 23, pp. 2403-2413, 2014.
97. E.N. Glaros, W. S. Kim, K.-A. Rye, J. A. Shayman, and B. Garner, Reduction of plasma glycosphingolipid levels has no impact on atherosclerosis in apolipoprotein E-null mice, Journal of Lipid Research, vol. 49, no. 8, pp. 1677-1681, 2008.
98. C. J. Knowles, M. Cebova, and I. M. Pinz, Palmitate dietinduced loss of cardiac caveolin-3: a novel mechanism for lipid-induced contractile dysfunction, PLoS ONE, vol. 8, no. 4, Article ID e61369, 2013.