1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Nutrition
  4. Volume 34, 2014
  5. Article

Annual Review of Nutrition

Volume 34, 2014

Lipid-Metabolizing CYPs in the Regulation and Dysregulation of Metabolism

Abstract

The cytochrome P450s (CYPs) represent a highly divergent class of enzymes involved in the oxidation of organic compounds. A subgroup of CYPs metabolize ω3-arachidonic and linoleic acids and ω6-docosahexaenoic and eicosapentaenoic polyunsaturated fatty acids (PUFAs) into a series of related biologically active mediators. Over the past 20 years, increasing evidence has emerged for a role of these PUFA-derived mediators in physiological and pathophysiological processes in the vasculature, during inflammation, and in the regulation of metabolism. With recent technological advances and increased availability of lipid mass spectroscopy, we are now starting to discern the patterns of these CYP-PUFA products in health and disease. These analyses not only are revealing the diverse spectrum of lipid nutrients regulated by CYPs, but also clearly indicate that the balance of these mediators changes with dietary intake of different PUFA classes. These findings suggest that we are only just beginning to understand all of the relevant lipid species produced by CYP pathways. Moreover, we are still a long way from understanding the nature and presence of their receptors, their tissue expression, and the pathophysiological processes they regulate. This review highlights these future issues in the context of lipid-metabolizing CYP enzymes, focusing particularly on the CYP450 family of epoxygenases and the lipid mediators they produce.

Keyword(s): CYP, eicosanoids, epoxygenase, polyunsaturated fatty acids
Loading

Article metrics loading...

/content/journals/10.1146/annurev-nutr-071813-105747
2014-07-17
2024-04-16
Loading full text...

Full text loading...

/deliver/fulltext/nutr/34/1/annurev-nutr-071813-105747.html?itemId=/content/journals/10.1146/annurev-nutr-071813-105747&mimeType=html&fmt=ahah

Literature Cited

  1. Aiba I, Yamasaki T, Shinki T, Izumi S, Yamamoto K. 1.  et al. 2006. Characterization of rat and human CYP2J enzymes as vitamin D 25-hydroxylases. Steroids 71:849–56 [Google Scholar]
  2. Alsaad AM, Zordoky BN, El-Sherbeni AA, El-Kadi AO. 2.  2012. Chronic doxorubicin cardiotoxicity modulates cardiac cytochrome P450-mediated arachidonic acid metabolism in rats. Drug Metab. Dispos. 40:2126–35 [Google Scholar]
  3. Amlani S, Nadarajah T, McIvor RA. 3.  2011. Montelukast for the treatment of asthma in the adult population. Expert Opin. Pharmacother. 12:2119–28 [Google Scholar]
  4. Anwar-Mohamed A, El-Sherbeni AA, Kim SH, Althurwi HN, Zordoky BNM, El-Kadi AOS. 4.  2012. Acute arsenic toxicity alters cytochrome P450 and soluble epoxide hydrolase and their associated arachidonic acid metabolism in C57Bl/6 mouse heart. Xenobiotica 42:1235–47 [Google Scholar]
  5. Arnold C, Markovic M, Blossey K, Wallukat G, Fischer R. 5.  et al. 2010. Arachidonic acid-metabolizing cytochrome P450 enzymes are targets of omega-3 fatty acids. J. Biol. Chem. 285:32720–33 [Google Scholar]
  6. Askari A, Thomson SJ, Edin ML, Zeldin DC, Bishop-Bailey D. 6.  2013. Roles of the epoxygenase CYP2J2 in the endothelium. Prostaglandins Other Lipid Mediat. 107:56–63 [Google Scholar]
  7. Bahl CD, Madden DR. 7.  2012. Pseudomonas aeruginosa Cif defines a distinct class of alpha/beta epoxide hydrolases utilizing a His/Tyr ring-opening pair. Protein Pept. Lett. 19:186–93 [Google Scholar]
  8. Bannenberg GL. 8.  2010. Therapeutic applicability of anti-inflammatory and proresolving polyunsaturated fatty acid-derived lipid mediators. ScientificWorldJournal 10:676–712 [Google Scholar]
  9. Baylie RL, Brayden JE. 9.  2010. TRPV channels and vascular function. Acta Physiol. (Oxf.) 203:99–116 [Google Scholar]
  10. Berger J, Moller DE. 10.  2002. The mechanisms of action of PPARs. Annu. Rev. Med. 53:409–35 [Google Scholar]
  11. Bieche I, Narjoz C, Asselah T, Vacher S, Marcellin P. 11.  et al. 2007. Reverse transcriptase-PCR quantification of mRNA levels from cytochrome (CYP)1, CYP2 and CYP3 families in 22 different human tissues. Pharmacogenet. Genomics 17:731–42 [Google Scholar]
  12. Bishop-Bailey D, Bystrom J. 12.  2009. Emerging roles of peroxisome proliferator-activated receptor-beta/delta in inflammation. Pharmacol. Ther. 124:141–50 [Google Scholar]
  13. Bishop-Bailey D, Wray J. 13.  2003. Peroxisome proliferator-activated receptors: a critical review on endogenous pathways for ligand generation. Prostaglandins Other Lipid Mediat. 71:1–22 [Google Scholar]
  14. Botham KM, Wheeler-Jones CP. 14.  2013. Postprandial lipoproteins and the molecular regulation of vascular homeostasis. Prog. Lipid Res. 52:446–64 [Google Scholar]
  15. Burgess APH, Vanella L, Bellner L, Gotlinger K, Falck JR. 15.  et al. 2012. Heme oxygenase (HO-1) rescue of adipocyte dysfunction in HO-2 deficient mice via recruitment of epoxyeicosatrienoic acids (EETs) and adiponectin. Cell. Physiol. Biochem. 29:99–110 [Google Scholar]
  16. Burke JE, Dennis EA. 16.  2009. Phospholipase A2 structure/function, mechanism, and signaling. J. Lipid Res. 50:Suppl.S237–42 [Google Scholar]
  17. Bystrom J, Thomson SJ, Johansson J, Edin ML, Zeldin DC. 17.  et al. 2013. Inducible CYP2J2 and its product 11,12-EET promotes bacterial phagocytosis: a role for CYP2J2 deficiency in the pathogenesis of Crohn's disease?. PLoS ONE 8:e75107 [Google Scholar]
  18. Bystrom J, Wray JA, Sugden MC, Holness MJ, Swales KE. 18.  et al. 2011. Endogenous epoxygenases are modulators of monocyte/macrophage activity. PLoS ONE 6:e26591 [Google Scholar]
  19. Capdevila JH, Falck JR, Harris RC. 19.  2000. Cytochrome P450 and arachidonic acid bioactivation. Molecular and functional properties of the arachidonate monooxygenase. J. Lipid Res. 41:163–81 [Google Scholar]
  20. Chen GZ, Xu RF, Wang YN, Wang PH, Zhao G. 20.  et al. 2012. Genetic disruption of soluble epoxide hydrolase is protective against streptozotocin-induced diabetic nephropathy. Am. J. Physiol. Endocrinol. Metab. 303:E563–75 [Google Scholar]
  21. Chen L, Fan C, Zhang Y, Bakri M, Dong H. 21.  et al. 2013. Beneficial effects of inhibition of soluble epoxide hydrolase on glucose homeostasis and islet damage in a streptozotocin-induced diabetic mouse model. Prostaglandins Other Lipid Mediat. 104–105:42–48 [Google Scholar]
  22. Chen Y, Goldstein JA. 22.  2009. The transcriptional regulation of the human CYP2C genes. Curr. Drug Metab. 10:567–78 [Google Scholar]
  23. Cheranov SY, Karpurapu M, Wang D, Zhang B, Venema RC, Rao GN. 23.  2008. An essential role for SRC-activated STAT-3 in 14,15-EET-induced VEGF expression and angiogenesis. Blood 111:5581–91 [Google Scholar]
  24. Cong S, Ma XT, Li YX, Wang JF. 24.  2013. Structural basis for the mutation-induced dysfunction of human CYP2J2: a computational study. J. Chem. Inf. Model. 53:1350–57 [Google Scholar]
  25. Cowart LA, Wei S, Hsu MH, Johnson EF, Krishna MU. 25.  et al. 2002. The CYP4A isoforms hydroxylate epoxyeicosatrienoic acids to form high affinity peroxisome proliferator-activated receptor ligands. J. Biol. Chem. 277:35105–12 [Google Scholar]
  26. Daikh BE, Lasker JM, Raucy JL, Koop DR. 26.  1994. Regio- and stereoselective epoxidation of arachidonic acid by human cytochromes P450 2C8 and 2C9. J. Pharmacol. Exp. Ther. 271:1427–33 [Google Scholar]
  27. De Taeye BM, Morisseau C, Coyle J, Covington JW, Luria A. 27.  et al. 2010. Expression and regulation of soluble epoxide hydrolase in adipose tissue. Obesity(Silver Spring) 18:489–98 [Google Scholar]
  28. Decker M, Adamska M, Cronin A, Di Giallonardo F, Burgener J. 28.  et al. 2012. EH3 (ABHD9): the first member of a new epoxide hydrolase family with high activity for fatty acid epoxides. J. Lipid Res. 53:2038–45 [Google Scholar]
  29. Deng Y, Theken KN, Lee CR. 29.  2010. Cytochrome P450 epoxygenases, soluble epoxide hydrolase, and the regulation of cardiovascular inflammation. J. Mol. Cell Cardiol. 48:331–41 [Google Scholar]
  30. Dewey S, Lai X, Witzmann FA, Sohal M, Gomes AV. 30.  2013. Proteomic analysis of hearts from Akita mice suggests that increases in soluble epoxide hydrolase and antioxidative programming are key changes in early stages of diabetic cardiomyopathy. J. Proteome Res. 12:3920–33 [Google Scholar]
  31. Earley S, Heppner TJ, Nelson MT, Brayden JE. 31.  2005. TRPV4 forms a novel Ca2+ signaling complex with ryanodine receptors and BKCa channels. Circ. Res. 97:1270–79 [Google Scholar]
  32. Edin ML, Wang Z, Bradbury JA, Graves JP, Lih FB. 32.  et al. 2011. Endothelial expression of human cytochrome P450 epoxygenase CYP2C8 increases susceptibility to ischemia-reperfusion injury in isolated mouse heart. FASEB J. 25:3436–47 [Google Scholar]
  33. Fleming I. 33.  2011. The cytochrome P450 pathway in angiogenesis and endothelial cell biology. Cancer Metastasis Rev. 30:541–55 [Google Scholar]
  34. Guedes AGP, Morisseau C, Sole A, Soares JHN, Ulu A. 34.  et al. 2013. Use of a soluble epoxide hydrolase inhibitor as an adjunctive analgesic in a horse with laminitis. Vet. Anaesth. Analg. 40:440–48 [Google Scholar]
  35. Hartweg J, Farmer AJ, Holman RR, Neil HA. 35.  2007. Meta-analysis of the effects of n-3 polyunsaturated fatty acids on haematological and thrombogenic factors in type 2 diabetes. Diabetologia 50:250–58 [Google Scholar]
  36. Hillig T, Krustrup P, Fleming I, Osada T, Saltin B, Hellsten Y. 36.  2003. Cytochrome P450 2C9 plays an important role in the regulation of exercise-induced skeletal muscle blood flow and oxygen uptake in humans. J. Physiol. 546:307–14 [Google Scholar]
  37. Holness MJ, Smith ND, Bulmer K, Hopkins T, Gibbons GF, Sugden MC. 37.  2002. Evaluation of the role of peroxisome-proliferator-activated receptor alpha in the regulation of cardiac pyruvate dehydrogenase kinase 4 protein expression in response to starvation, high-fat feeding and hyperthyroidism. Biochem. J. 364:687–94 [Google Scholar]
  38. Imig JD. 38.  2012. Epoxides and soluble epoxide hydrolase in cardiovascular physiology. Physiol. Rev. 92:101–30 [Google Scholar]
  39. Inceoglu B, Wagner KM, Yang J, Bettaieb A, Schebb NH. 39.  et al. 2012. Acute augmentation of epoxygenated fatty acid levels rapidly reduces pain-related behavior in a rat model of type I diabetes. Proc. Natl. Acad. Sci. USA 109:11390–95 [Google Scholar]
  40. Jiang H, Anderson GD, McGiff JC. 40.  2012. The red blood cell participates in regulation of the circulation by producing and releasing epoxyeicosatrienoic acids. Prostaglandins Other Lipid Mediat. 98:91–93 [Google Scholar]
  41. Jiang H, Zhu AG, Mamczur M, Falck JR, Lerea KM, McGiff JC. 41.  2007. Stimulation of rat erythrocyte P2X7 receptor induces the release of epoxyeicosatrienoic acids. Br. J. Pharmacol. 151:1033–40 [Google Scholar]
  42. Johnson JA, Cavallari LH. 42.  2013. Pharmacogenetics and cardiovascular disease—implications for personalized medicine. Pharmacol. Rev. 65:987–1009 [Google Scholar]
  43. Jouihan SA, Zuloaga KL, Zhang WR, Shangraw RE, Krasnow SM. 43.  et al. 2013. Role of soluble epoxide hydrolase in exacerbation of stroke by streptozotocin-induced type 1 diabetes mellitus. J. Cereb. Blood Flow Metab. 33:1650–56 [Google Scholar]
  44. Jump DB, Depner CM, Tripathy S. 44.  2012. Omega-3 fatty acid supplementation and cardiovascular disease. J. Lipid Res. 53:2525–45 [Google Scholar]
  45. Klett EL, Chen S, Edin ML, Li LO, Ilkayeva O. 45.  et al. 2013. Diminished acyl-CoA synthetase isoform 4 activity in INS 832/13 cells reduces cellular epoxyeicosatrienoic acid levels and results in impaired glucose-stimulated insulin secretion. J. Biol. Chem. 288:21618–29 [Google Scholar]
  46. Komura H, Iwaki M. 46.  2011. In vitro and in vivo small intestinal metabolism of CYP3A and UGT substrates in preclinical animals species and humans: species differences. Drug Metab. Rev. 43:476–98 [Google Scholar]
  47. Kraus-Friedmann N, Feng L. 47.  1996. The role of intracellular Ca2+ in the regulation of gluconeogenesis. Metabolism 45:389–403 [Google Scholar]
  48. Kundu S, Roome T, Bhattacharjee A, Carnevale KA, Yakubenko VP. 48.  et al. 2013. Metabolic products of soluble epoxide hydrolase are essential for monocyte chemotaxis to MCP-1 in vitro and in vivo. J. Lipid Res. 54:436–47 [Google Scholar]
  49. Lai XS, Yang LP, Li XT, Liu JP, Zhou ZW, Zhou SF. 49.  2009. Human CYP2C8: structure, substrate specificity, inhibitor selectivity, inducers and polymorphisms. Curr. Drug Metab. 10:1009–47 [Google Scholar]
  50. Larsen BT, Miura H, Hatoum OA, Campbell WB, Hammock BD. 50.  et al. 2006. Epoxyeicosatrienoic and dihydroxyeicosatrienoic acids dilate human coronary arterioles via BK(Ca) channels: implications for soluble epoxide hydrolase inhibition. Am J. Physiol. Heart Circ. Physiol. 290:H491–99 [Google Scholar]
  51. Lee CA, Jones JP 3rd, Katayama J, Kaspera R, Jiang Y. 51.  et al. 2012. Identifying a selective substrate and inhibitor pair for the evaluation of CYP2J2 activity. Drug Metab. Dispos. 40:943–51 [Google Scholar]
  52. Lee CA, Neul D, Clouser-Roche A, Dalvie D, Wester MR. 52.  et al. 2010. Identification of novel substrates for human cytochrome P450 2J2. Drug Metab. Dispos. 38:347–56 [Google Scholar]
  53. Lee CR, Imig JD, Edin ML, Foley J, DeGraff LM. 53.  et al. 2010. Endothelial expression of human cytochrome P450 epoxygenases lowers blood pressure and attenuates hypertension-induced renal injury in mice. FASEB J. 24:3770–81 [Google Scholar]
  54. Li PL, Campbell WB. 54.  1997. Epoxyeicosatrienoic acids activate K+ channels in coronary smooth muscle through a guanine nucleotide binding protein. Circ. Res. 80:877–84 [Google Scholar]
  55. Liu Y, Zhang Y, Schmelzer K, Lee TS, Fang X. 55.  et al. 2005. The antiinflammatory effect of laminar flow: the role of PPARγ, epoxyeicosatrienoic acids, and soluble epoxide hydrolase. Proc. Natl. Acad. Sci. USA 102:16747–52 [Google Scholar]
  56. Lundstrom SL, Yang J, Brannan JD, Haeggstrom JZ, Hammock BD. 56.  et al. 2013. Lipid mediator serum profiles in asthmatics significantly shift following dietary supplementation with omega-3 fatty acids. Mol. Nutr. Food Res. 57:1378–89 [Google Scholar]
  57. Luo P, Chang HH, Zhou Y, Zhang S, Hwang SH. 57.  et al. 2010. Inhibition or deletion of soluble epoxide hydrolase prevents hyperglycemia, promotes insulin secretion, and reduces islet apoptosis. J. Pharmacol. Exp. Ther. 334:430–38 [Google Scholar]
  58. Luria A, Bettaieb A, Xi Y, Shieh GJ, Liu HC. 58.  et al. 2011. Soluble epoxide hydrolase deficiency alters pancreatic islet size and improves glucose homeostasis in a model of insulin resistance. Proc. Natl. Acad. Sci. USA 108:9038–43 [Google Scholar]
  59. Majkova Z, Layne J, Sunkara M, Morris AJ, Toborek M, Hennig B. 59.  2011. Omega-3 fatty acid oxidation products prevent vascular endothelial cell activation by coplanar polychlorinated biphenyls. Toxicol. Appl. Pharmacol. 251:41–49 [Google Scholar]
  60. Markworth JF, Vella LD, Lingard BS, Tull DL, Rupasinghe TW. 60.  et al. 2013. Human inflammatory and resolving lipid mediator responses to resistance exercise and ibuprofen treatment. Am. J. Physiol. Regul. Integr. Comp. Physiol. 305:R1281–96 [Google Scholar]
  61. Michaelis UR, Fisslthaler B, Medhora M, Harder D, Fleming I, Busse R. 61.  2003. Cytochrome P450 2C9-derived epoxyeicosatrienoic acids induce angiogenesis via cross-talk with the epidermal growth factor receptor (EGFR). FASEB J. 17:770–72 [Google Scholar]
  62. Michaud V, Frappier M, Dumas MC, Turgeon J. 62.  2010. Metabolic activity and mRNA levels of human cardiac CYP450s involved in drug metabolism. PLoS ONE 5:e15666 [Google Scholar]
  63. Minamiyama Y, Takemura S, Imaoka S, Funae Y, Okada S. 63.  2007. Cytochrome P450 is responsible for nitric oxide generation from NO-aspirin and other organic nitrates. Drug Metab. Pharmacokinet. 22:15–19 [Google Scholar]
  64. Mitra R, Guo Z, Milani M, Mesaros C, Rodriguez M. 64.  et al. 2011. CYP3A4 mediates growth of estrogen receptor-positive breast cancer cells in part by inducing nuclear translocation of phospho-Stat3 through biosynthesis of (±)-14,15-epoxyeicosatrienoic acid (EET). J. Biol. Chem. 286:17543–59 [Google Scholar]
  65. Moraes LA, Piqueras L, Bishop-Bailey D. 65.  2006. Peroxisome proliferator-activated receptors and inflammation. Pharmacol. Ther. 110:371–85 [Google Scholar]
  66. Morisseau C, Hammock BD. 66.  2013. Impact of soluble epoxide hydrolase and epoxyeicosanoids on human health. Annu. Rev. Pharmacol. Toxicol. 53:37–58 [Google Scholar]
  67. Nebert DW, Wikvall K, Miller WL. 67.  2013. Human cytochromes P450 in health and disease. Philos. Trans. R. Soc. B 368:20120431 [Google Scholar]
  68. Nelson DR. 68.  2009. The cytochrome p450 homepage. Hum. Genomics 4:59–65 [Google Scholar]
  69. Norris PC, Dennis EA. 69.  2014. A lipidomic perspective on inflammatory macrophage eicosanoid signaling. Adv. Biol. Regul. 54C:99–110 [Google Scholar]
  70. Oliw EH. 70.  1984. Metabolism of 5(6)-expoxyeicosatrienoic acid by ram seminal vesicles. Formation of novel prostaglandin E1 metabolites. Biochim. Biophys. Acta 793:408–15 [Google Scholar]
  71. Panigrahy D, Edin ML, Lee CR, Huang S, Bielenberg DR. 71.  et al. 2012. Epoxyeicosanoids stimulate multiorgan metastasis and tumor dormancy escape in mice. J. Clin. Invest. 122:178–91 [Google Scholar]
  72. Panigrahy D, Greene ER, Pozzi A, Wang DW, Zeldin DC. 72.  2011. EET signaling in cancer. Cancer Metastasis Rev. 30:525–40 [Google Scholar]
  73. Panigrahy D, Kalish BT, Huang S, Bielenberg DR, Le HD. 73.  et al. 2013. Epoxyeicosanoids promote organ and tissue regeneration. Proc. Natl. Acad. Sci. USA 110:13528–33 [Google Scholar]
  74. Potente M, Fisslthaler B, Busse R, Fleming I. 74.  2003. 11,12-Epoxyeicosatrienoic acid-induced inhibition of FOXO factors promotes endothelial proliferation by down-regulating p27Kip1. J. Biol. Chem. 278:29619–25 [Google Scholar]
  75. Rizos EC, Ntzani EE, Bika E, Kostapanos MS, Elisaf MS. 75.  2012. Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systematic review and meta-analysis. JAMA 308:1024–33 [Google Scholar]
  76. Roberts LJ 2nd, Fessel JP, Davies SS. 76.  2005. The biochemistry of the isoprostane, neuroprostane, and isofuran pathways of lipid peroxidation. Brain Pathol. 15:143–48 [Google Scholar]
  77. Ross AC, Zolfaghari R. 77.  2011. Cytochrome P450s in the regulation of cellular retinoic acid metabolism. Annu. Rev. Nutr. 31:65–87 [Google Scholar]
  78. Sacerdoti D, Gatta A, McGiff JC. 78.  2003. Role of cytochrome P450-dependent arachidonic acid metabolites in liver physiology and pathophysiology. Prostaglandins Other Lipid Mediat. 72:51–71 [Google Scholar]
  79. Schuchardt JP, Schmidt S, Kressel G, Dong H, Willenberg I. 79.  et al. 2013. Comparison of free serum oxylipin concentrations in hyper- versus normolipidemic men. Prostaglandins Leukot. Essent. Fatty Acids 89:19–29 [Google Scholar]
  80. Serhan CN. 80.  2010. Novel lipid mediators and resolution mechanisms in acute inflammation: to resolve or not?. Am. J. Pathol. 177:1576–91 [Google Scholar]
  81. Seubert J, Yang B, Bradbury JA, Graves J, Degraff LM. 81.  et al. 2004. Enhanced postischemic functional recovery in CYP2J2 transgenic hearts involves mitochondrial ATP-sensitive K+ channels and p42/p44 MAPK pathway. Circ. Res. 95:506–14 [Google Scholar]
  82. Smilowitz JT, Zivkovic AM, Wan YJ, Watkins SM, Nording ML. 82.  et al. 2013. Nutritional lipidomics: molecular metabolism, analytics, and diagnostics. Mol. Nutr. Food Res. 57:1319–35 [Google Scholar]
  83. Sodhi K, Inoue K, Gotlinger KH, Canestraro M, Vanella L. 83.  et al. 2009. Epoxyeicosatrienoic acid agonist rescues the metabolic syndrome phenotype of HO-2-null mice. J. Pharmacol. Exp. Ther. 331:906–16 [Google Scholar]
  84. Spector AA. 84.  2009. Arachidonic acid cytochrome P450 epoxygenase pathway. J. Lipid Res. 50:Suppl.S52–56 [Google Scholar]
  85. Swales KE, Moore R, Truss NJ, Tucker A, Warner TD. 85.  et al. 2012. Pregnane X receptor regulates drug metabolism and transport in the vasculature and protects from oxidative stress. Cardiovasc. Res. 93:674–81 [Google Scholar]
  86. Thomson SJ, Askari A, Bishop-Bailey D. 86.  2012. Anti-inflammatory effects of epoxyeicosatrienoic acids. Int. J. Vasc. Med. 2012:605101 [Google Scholar]
  87. Vriens J, Owsianik G, Fisslthaler B, Suzuki M, Janssens A. 87.  et al. 2005. Modulation of the Ca2 permeable cation channel TRPV4 by cytochrome P450 epoxygenases in vascular endothelium. Circ. Res. 97:908–15 [Google Scholar]
  88. Wamberg L, Christiansen T, Paulsen SK, Fisker S, Rask P. 88.  et al. 2013. Expression of vitamin D-metabolizing enzymes in human adipose tissue—the effect of obesity and diet-induced weight loss. Int. J. Obes.(Lond.) 37:651–57 [Google Scholar]
  89. Wang Y, Wei X, Xiao X, Hui R, Card JW. 89.  et al. 2005. Arachidonic acid epoxygenase metabolites stimulate endothelial cell growth and angiogenesis via mitogen-activated protein kinase and phosphatidylinositol 3-kinase/Akt signaling pathways. J. Pharmacol. Exp. Ther. 314:522–32 [Google Scholar]
  90. Warner TD, Mitchell JA. 90.  2004. Cyclooxygenases: new forms, new inhibitors, and lessons from the clinic. FASEB J. 18:790–804 [Google Scholar]
  91. Watanabe H, Vriens J, Prenen J, Droogmans G, Voets T, Nilius B. 91.  2003. Anandamide and arachidonic acid use epoxyeicosatrienoic acids to activate TRPV4 channels. Nature 424:434–38 [Google Scholar]
  92. Westphal C, Konkel A, Schunck WH. 92.  2011. CYP-eicosanoids—a new link between omega-3 fatty acids and cardiac disease?. Prostaglandins Other Lipid Mediat. 96:99–108 [Google Scholar]
  93. Williams PA, Cosme J, Ward A, Angove HC, Matak Vinkovic D, Jhoti H. 93.  2003. Crystal structure of human cytochrome P450 2C9 with bound warfarin. Nature 424:464–68 [Google Scholar]
  94. Wong PY, Lin KT, Yan YT, Ahern D, Iles J. 94.  et al. 1993. 14(R),15(S)-epoxyeicosatrienoic acid (14(R),15(S)-EET) receptor in guinea pig mononuclear cell membranes. J. Lipid Mediat. 6:199–208 [Google Scholar]
  95. Wray JA, Sugden MC, Zeldin DC, Greenwood GK, Samsuddin S. 95.  et al. 2009. The epoxygenases CYP2J2 activates the nuclear receptor PPARα in vitro and in vivo. PLoS ONE 4:e7421 [Google Scholar]
  96. Xu X, Zhang XA, Wang DW. 96.  2011. The roles of CYP450 epoxygenases and metabolites, epoxyeicosatrienoic acids, in cardiovascular and malignant diseases. Adv. Drug Deliv. Rev. 63:597–609 [Google Scholar]
  97. Xu XZ, Tu L, Feng WJ, Ma B, Li R. 97.  et al. 2013. CYP2J3 gene delivery up-regulated adiponectin expression via reduced endoplasmic reticulum stress in adipocytes. Endocrinology 154:1743–53 [Google Scholar]
  98. Xu XZ, Zhao CX, Wang LY, Tu L, Fang XS. 98.  et al. 2010. Increased CYP2J3 expression reduces insulin resistance in fructose-treated rats and db/db mice. Diabetes 59:997–1005 [Google Scholar]
  99. Yan G, Chen S, You B, Sun J. 99.  2008. Activation of sphingosine kinase-1 mediates induction of endothelial cell proliferation and angiogenesis by epoxyeicosatrienoic acids. Cardiovasc. Res. 78:308–14 [Google Scholar]
  100. Yoshida S, Hirai A, Tamura Y. 100.  1990. Possible involvement of arachidonic acid metabolites of cytochrome P450 monooxygenase pathway in vasopressin-stimulated glycogenolysis in isolated rat hepatocytes. Arch. Biochem. Biophys. 280:346–51 [Google Scholar]
  101. Zanger UM, Schwab M. 101.  2013. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol. Ther. 138:103–41 [Google Scholar]
  102. Zeldin DC. 102.  2001. Epoxygenase pathways of arachidonic acid metabolism. J. Biol. Chem. 276:36059–62 [Google Scholar]
  103. Zeldin DC, Foley J, Boyle JE, Moomaw CR, Tomer KB. 103.  et al. 1997. Predominant expression of an arachidonate epoxygenase in islets of Langerhans cells in human and rat pancreas. Endocrinology 138:1338–46 [Google Scholar]
  104. Zeldin DC, Wei S, Falck JR, Hammock BD, Snapper JR, Capdevila JH. 104.  1995. Metabolism of epoxyeicosatrienoic acids by cytosolic epoxide hydrolase: substrate structural determinants of asymmetric catalysis. Arch. Biochem. Biophys. 316:443–51 [Google Scholar]
  105. Zhang B, Cao H, Rao GN. 105.  2006. Fibroblast growth factor-2 is a downstream mediator of phosphatidyl-inositol 3-kinase-Akt signaling in 14,15-epoxyeicosatrienoic acid-induced angiogenesis. J. Biol. Chem. 281:905–14 [Google Scholar]
  106. Zhang G, Panigrahy D, Mahakian LM, Yang J, Liu JY. 106.  et al. 2013. Epoxy metabolites of docosahexaenoic acid (DHA) inhibit angiogenesis, tumor growth, and metastasis. Proc. Natl. Acad. Sci. USA 110:6530–35 [Google Scholar]
  107. Zhang LN, Vincelette J, Cheng Y, Mehra U, Chen D. 107.  et al. 2009. Inhibition of soluble epoxide hydrolase attenuated atherosclerosis, abdominal aortic aneurysm formation, and dyslipidemia. Arterioscler. Thromb. Vasc. Biol. 29:1265–70 [Google Scholar]
/content/journals/10.1146/annurev-nutr-071813-105747
Loading
Lipid-Metabolizing CYPs in the Regulation and Dysregulation of Metabolism
Annual Review of Nutrition 34, 261 (2014); https://doi.org/10.1146/annurev-nutr-071813-105747
/content/journals/10.1146/annurev-nutr-071813-105747
/content/journals/10.1146/annurev-nutr-071813-105747
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error