Metabolic effects of achronic dietaryexposure to a low-dose pesticide cocktail in mice: Sexual dimorphism and role of the constitutive and rostane receptor

Environmental Health Perspectives

Volumn 126, Issue 6, 2018, Pages

  Lukowicz, Céline ^a   Simatos, Sandrine Ellero ^a   Régnier, Marion ^a   Polizzi, Arnaud ^a   Lasserre, Frédéric ^a   Montagner, Alexandra ^a   Lippi, Yannick ^a   Jamin, Emilien L ^a,c   Martin, Jean François ^a   Naylies, Claire ^a   Canlet, Cécile ^a,c   Debrauwer, Laurent ^a,c   Bertrand Michel, Justine ^b   Saati, Talal Al ^d   Théodorou, Vassilia ^a   Loiseau, Nicolas ^a   Lakhal, Laïla Mselli ^a   Guillou, Hervé ^a   Gamet Payrastre, Laurence ^a  

^a TOXALIM RESEARCH CENTRE IN FOOD TOXICOLOGY   (France)

^b Université de Toulouse   (France)

^c National Infrastructure for Metabolomics and Fluxomics   (France)

^d CHU PURPAN   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE AMINOTRANSFERASE; ASPARTATE AMINOTRANSFERASE; BOSCALID; CAPTAN; CHLORPYRIFOS; CHOLESTEROL; CONSTITUTIVE ANDROSTANE RECEPTOR; FATTY ACID; GLUCOSE; GLUTATHIONE; GLUTATHIONE DISULFIDE; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LOW DENSITY LIPOPROTEIN CHOLESTEROL; PESTICIDE; THIACLOPRID; THIOFANATE; TRIACYLGLYCEROL; UNCLASSIFIED DRUG; ZIRAM; CELL RECEPTOR; FUNGICIDE; INSECTICIDE;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BODY WEIGHT GAIN; CONTROLLED STUDY; DIETARY INTAKE; ENZYME LINKED IMMUNOSORBENT ASSAY; FATTY ACID ANALYSIS; FATTY LIVER; FEMALE; GENE EXPRESSION; GLUCOSE INTOLERANCE; GLUCOSE TOLERANCE TEST; HISTOLOGY; HYPERGLYCEMIA; LIQUID CHROMATOGRAPHY-MASS SPECTROMETRY; LIVER METABOLISM; LONG TERM EXPOSURE; MALE; MASS FRAGMENTOGRAPHY; METABOLIC PARAMETERS; METABOLOME; METABOLOMICS; MOUSE; NONHUMAN; OBESITY; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTON NUCLEAR MAGNETIC RESONANCE; REAL TIME POLYMERASE CHAIN REACTION; RISK FACTOR; SEX DIFFERENCE; SURVIVAL; UPREGULATION; URINALYSIS; WHITE ADIPOSE TISSUE; ANIMAL; BODY WEIGHT; C57BL MOUSE; CHEMICALLY INDUCED; DIETARY EXPOSURE; DISORDERS OF CARBOHYDRATE METABOLISM; DRUG EFFECT; DRUG INACTIVATION; GENETICS; LIVER; METABOLISM; SEX FACTOR; TOXICITY TESTING; TRANSGENIC ANIMAL;

ANIMALS; ANIMALS, GENETICALLY MODIFIED; BODY WEIGHT; DIETARY EXPOSURE; FATTY LIVER; FEMALE; FUNGICIDES, INDUSTRIAL; GLUCOSE METABOLISM DISORDERS; GLUTATHIONE; INACTIVATION, METABOLIC; INSECTICIDES; LIVER; MALE; METABOLOME; MICE; MICE, INBRED C57BL; RECEPTORS, CYTOPLASMIC AND NUCLEAR; SEX FACTORS; TOXICITY TESTS, CHRONIC;

EID: 85049230030     PISSN: 00916765     EISSN: 15529924     Source Type: Journal    
DOI: 10.1289/EHP2877     Document Type: Article

References (92)

1. Abass K, Pelkonen O. 2013. The inhibition of major human hepatic cytochrome P450 enzymes by 18 pesticides: comparison of the N-in-one and single substrate approaches. Toxicol In Vitr 27(5):1584–1588, PMID: 22634058, 10.1016/j.tiv.2012.05.003.
2. Adigun AA, Ryde IT, Seidler FJ, Slotkin TA. 2010a. Organophosphate exposure during a critical developmental stage reprograms adenylyl cyclase signaling in PC12 cells. Brain Res 1329:36–44, PMID: 20298678, 10.1016/j.brainres.2010.03.025.
3. Adigun AA, Wrench N, Levin ED, Seidler FJ, Slotkin TA. 2010b. Neonatal parathion exposure and interactions with a high-fat diet in adulthood: adenylyl cyclase-mediated cell signaling in heart, liver and cerebellum. Brain Res Bull 81(6):605–612, PMID: 20074626, 10.1016/j.brainresbull.2010.01.003.
4. Al-Eryani L, Wahlang B, Falkner KC, Guardiola JJ, Clair HB, Prough RA, et al. 2015. Identification of environmental chemicals associated with the development of toxicant-associated fatty liver disease in rodents. Toxicol Pathol 43(4):482–497, PMID: 25326588, 10.1177/0192623314549960.
5. Anderson SP, Howroyd P, Liu J, Qian X, Bahnemann R, Swanson C, et al. 2004. The transcriptional response to a peroxisome proliferator-activated receptor alpha agonist includes increased expression of proteome maintenance genes. J Biol Chem 279(50):52390–52398, PMID: 15375163, 10.1074/jbc.M409347200.
6. Androutsopoulos VP, Hernandez AF, Liesivuori J, Tsatsakis AM. 2013. A mechanistic overview of health associated effects of low levels of organochlorine and organophosphorous pesticides. Toxicology 307:89–94, PMID: 23041710, 10.1016/j.tox.2012.09.011.
7. Arciello M, Gori M, Maggio R, Barbaro B, Tarocchi M, Galli A, et al. 2013. Environmental pollution: a tangible risk for NAFLD pathogenesis. Int J Mol Sci 14(11):22052–22066, PMID: 24213605, 10.3390/ijms141122052.
8. Armstrong LE, Driscoll MV, Donepudi AC, Xu J, Baker A, Aleksunes LM, et al. 2013. Effects of developmental deltamethrin exposure on white adipose tissue gene expression. J Biochem Mol Toxicol 27(2):165–171, PMID: 23401056, 10.1002/jbt.21477.
9. Baldwin WS, Roling JA. 2009. A Concentration addition model for the activation of the constitutive androstane receptor by xenobiotic mixtures. Toxicol Sci 107(1):93–105, PMID: 18832183, 10.1093/toxsci/kfn206.
10. Beckonert O, Keun HC, Ebbels TM, Bundy J, Holmes E, Lindon JC, et al. 2007. Metabolic profiling, metabolomic and metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts. Nat Protoc 2(11):2692–2703, PMID: 18007604, 10.1038/nprot.2007.376.
11. Bhaskar R, Mohanty B. 2014. Pesticides in mixture disrupt metabolic regulation: in silico and in vivo analysis of cumulative toxicity of mancozeb and imidacloprid on body weight of mice. Gen Comp Endocrinol 205:226–234, PMID: 24530807, 10.1016/j.ygcen.2014.02.007.
12. Bligh EG, Dyer WJ. 1959. A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37(8):911–917, PMID: 13671378, 10.1139/o59-099.
13. Bolstad BM, Irizarry RA, Astrand M, Speed TP. 2003. A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 19(2):185–193, PMID: 12538238, 10.1093/bioinformatics/19.2.185.
14. Bookout AL, Jeong Y, Downes M, Yu RT, Evans RM, Mangelsdorf DJ. 2006. Anatomical profiling of nuclear receptor expression reveals a hierarchical transcriptional network. Cell 126(4):789–799, PMID: 16923397, 10.1016/j.cell.2006.06.049.
15. Casals-Casas C, Desvergne B. 2011. Endocrine disruptors: from endocrine to metabolic disruption. Annu Rev Physiol 73:135–162, PMID: 21054169, 10.1146/annurev-physiol-012110-142200.
16. Chapados NA, Casimiro C, Robidoux MA, Haman F, Batal M, Blais JM, et al. 2012. Increased proliferative effect of organochlorine compounds on human preadipocytes. Mol Cell Biochem 365(1–2):275–278, PMID: 22350817, 10.1007/s11010-012-1268-0.
17. Chomczynski P, Sacchi N. 1987. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162(1):156–159, PMID: 2440339, 10.1016/0003-2697(87)90021-2.
18. Claus SP, Guillou H, Ellero-Simatos S. 2016. The gut microbiota: a major player in the toxicity of environmental pollutants? NPJ Biofilms Microbiomes 2:16003, PMID: 28721242, 10.1038/npjbiofilms.2016.3.
19. 1 H NMR data sets. Anal Chem 77(5):1282–1289, PMID: 15732908, 10.1021/ac048630x.
20. 1 H NMR spectroscopic metabonomic studies. Anal Chem 77(2):517–526, PMID: 15649048, 10.1021/ac048803i.
21. Craciun S, Balskus EP. 2012. Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme. Proc Natl Acad Sci USA 109(52):21307–21312, PMID: 23151509, 10.1073/pnas.1215689109.
22. Croom EL, Wallace AD, Hodgson E. 2010. Human variation in CYP-specific chlorpyrifos metabolism. Toxicology 276(3):184–191, PMID: 20709133, 10.1016/j.tox.2010.08.005.
23. Das KP, Wood CR, Lin MT, Starkov AA, Lau C, Wallace KB, et al. 2017. Perfluoroalkyl acids-induced liver steatosis: effects on genes controlling lipid homeostasis. Toxicology 378:37–52, PMID: 28049043, 10.1016/j.tox.2016.12.007.
24. De Long NE, Holloway AC. 2017. Early-life chemical exposures and risk of metabolic syndrome. Diabetes Metab Syndr Obes 10:101–109, PMID: 28367067, 10.2147/DMSO.S95296.
25. Delfosse V, Dendele B, Huet T, Grimaldi M, Boulahtouf A, Gerbal-Chaloin S, et al. 2015. Synergistic activation of human pregnane X receptor by binary cocktails of pharmaceutical and environmental compounds. Nat Commun 6:8089, PMID: 26333997, 10.1038/ncomms9089.
26. Della Morte R, Villani GR, Di Martino E, Squillacioti C, De Marco L, Vuotto P, et al. 1994. Glutathione depletion induced in rat liver fractions by seven pesticides. Boll Soc Ital Biol Sper 70(8–9):185–192, PMID: 7893475.
27. Desvergne B, Michalik L, Wahli W. 2006. Transcriptional regulation of metabolism. Physiol Rev 86(2):465–514, PMID: 16601267, 10.1152/physrev.00025.2005.
28. Dieterle F, Ross A, Schlotterbeck G, Senn H. 2006. Probabilistic quotient normalization as robust method to account for dilution of complex biological mixtures. Application in 1H NMR metabonomics. Anal Chem 78(13):4281–4290, PMID: 16808434, 10.1021/ac051632c.
29. Edgar R, Domrachev M, Lash AE. 2002. Gene expression omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res 30(1):207–210, PMID: 11752295, 10.1093/nar/30.1.207.
30. EFSA (European Food Safety Authority). 2015. The 2013 European Union report on pesticide residues in food. EFSA J 13(3):4038, 10.2903/j.efsa.2015.4038.
31. Evangelou E, Ntritsos G, Chondrogiorgi M, Kavvoura FK, Hernández AF, Ntzani EE, et al. 2016. Exposure to pesticides and diabetes: a systematic review and meta-analysis. Environ Int 91:60–68, PMID: 26909814, 10.1016/j.envint.2016.02.013.
32. Evans RM, Mangelsdorf DJ. 2014. Nuclear receptors, RXR, and the big bang. Cell 157(1):255–266, PMID: 24679540, 10.1016/j.cell.2014.03.012.
33. Feige JN, Gelman L, Rossi D, Zoete V, Métivier R, Tudor C, et al. 2007. The endocrine disruptor monoethyl-hexyl-phthalate is a selective peroxisome proliferator-activated receptor gamma modulator that promotes adipogenesis. J Biol Chem 282(26):19152–19166, PMID: 17468099, 10.1074/jbc.M702724200.
34. Flurkey K, Currer J, Harrison D. 2007. “Mouse models in aging research.” In: emFaculty Research 2000– 2009 em. https://mouseion.jax.org/stfb2000_2009/1685.
35. Fujino C, Tamura Y, Tange S, Nakajima H, Sanoh S, Watanabe Y, et al. 2016. Metabolism of methiocarb and carbaryl by rat and human livers and plasma, and effect on their PXR, CAR and PPARα activities. J Toxicol Sci 41(5):677–691, PMID: 27665777, 10.2131/jts.41.677.
36. Giacomoni F, Le Corguillé G, Monsoor M, Landi M, Pericard P, Pétéra M, et al. 2015. Workflow4Metabolomics: a collaborative research infrastructure for computational metabolomics. Bioinformatics 31(9):1493–1495, PMID: 25527831, 10.1093/bioinformatics/btu813.
37. Grün F, Blumberg B. 2009. Endocrine disrupters as obesogens. Mol Cell Endocrinol 304(1–2):19–29, PMID: 19433244, 10.1016/j.mce.2009.02.018.
38. Hagen J, Te Brinke H, Wanders RJ, Knegt AC, Oussoren E, Hoogeboom AJ, et al. 2015. Genetic basis of alpha-aminoadipic and alpha-ketoadipic aciduria. J Inherit Metab Dis 38(5):873–879, PMID: 25860818, 10.1007/s10545-015-9841-9.
39. Hong NS, Kim KS, Lee IK, Lind PM, Lind L, Jacobs DR, et al. 2012. The association between obesity and mortality in the elderly differs by serum concentrations of persistent organic pollutants: a possible explanation for the obesity paradox. Int J Obes (Lond) 36(9):1170–1175, PMID: 21946706, 10.1038/ijo.2011.187.
40. Howell GE III, Mulligan C, Meek E, Chambers JE. 2015. Effect of chronic p, p′-dichlorodiphenyldichloroethylene (DDE) exposure on high fat diet-induced alterations in glucose and lipid metabolism in male C57BL/6H mice. Toxicology 328:112–122, PMID: 25541407, 10.1016/j.tox.2014.12.017.
41. Huang da W, Sherman BT, Lempicki RA. 2009a. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 37(1):1–13, PMID: 19033363, 10.1093/nar/gkn923.
42. Huang da W, Sherman BT, Lempicki RA. 2009b. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4(1):44–57, PMID: 19131956, 10.1038/nprot.2008.211.
43. Huang W, Zhang J, Washington M, Liu J, Parant JM, Lozano G, et al. 2005. Xenobiotic stress induces hepatomegaly and liver tumors via the nuclear receptor constitutive androstane receptor. Mol Endocrinol 19(6):1646–1653, PMID: 15831521, 10.1210/me.2004-0520.
44. Hui Z, Li R, Chen L. 2017. The impact of exposure to environmental contaminant on hepatocellular lipid metabolism. Gene 622:67–71, PMID: 28431976, 10.1016/j.gene.2017.04.024.
45. Jamin EL, Bonvallot N, Tremblay-Franco M, Cravedi JP, Chevrier C, Cordier S, et al. 2014. Untargeted profiling of pesticide metabolites by LC-HRMS: an exposomics tool for human exposure evaluation. Anal Bioanal Chem 406(4):1149–1161, PMID: 23892877, 10.1007/s00216-013-7136-2.
46. Jin Y, Lin X, Miao W, Wu T, Shen H, Chen S, et al. 2014. Chronic exposure of mice to environmental endocrine-disrupting chemicals disturbs their energy metabolism. Toxicol Lett 225(3):392–400, PMID: 24440342, 10.1016/j.toxlet.2014.01.006.
47. Kamath V, Rajini P. 2007. Altered glucose homeostasis and oxidative impairment in pancreas of rats subjected to dimethoate intoxication. Toxicology 231(2-3):137–146, PMID: 17197067, 10.1016/j.tox.2006.11.072.
48. Karmaus W, Osuch JR, Eneli I, Mudd LM, Zhang J, Mikucki D, et al. 2009. Maternal levels of dichlorodiphenyl-dichloroethylene (DDE) may increase weight and body mass index in adult female offspring. Occup Environ Med 66(3):143–149, PMID: 19060027, 10.1136/oem.2008.041921.
49. Kim J, Park Y, Yoon KS, Clark JM, Park Y. 2013. Imidacloprid, a neonicotinoid insecticide, induces insulin resistance. J Toxicol Sci 38(5):655–660, PMID: 24025781, 10.2131/jts.38.655.
50. Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, et al. 2005. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 41(6):1313–1321, PMID: 15915461, 10.1002/hep.20701.
51. Klipper-Aurbach Y, Wasserman M, Braunspiegel-Weintrob N, Borstein D, Peleg S, Assa S, et al. 1995. Mathematical formulae for the prediction of the residual beta cell function during the first two years of disease in children and adolescents with insulin-dependent diabetes mellitus. Med Hypotheses 45(5):486–490, PMID: 8748093, 10.1016/0306-9877(95)90228-7.
52. Lasram MM, Dhouib IB, Bouzid K, Lamine AJ, Annabi A, Belhadjhmida N, et al. 2014. Association of inflammatory response and oxidative injury in the pathogenesis of liver steatosis and insulin resistance following subchronic exposure to malathion in rats. Environ Toxicol Pharmacol 38(2):542–553, PMID: 25180440, 10.1016/j.etap.2014.08.007.
53. Lasram MM, El-Golli N, Lamine AJ, Douib IB, Bouzid K, Annabi A, et al. 2015. Changes in glucose metabolism and reversion of genes expression in the liver of insulin-resistant rats exposed to malathion. The protective effects of N-acetylcysteine. Gen Comp Endocrinol 215:88–97, PMID: 25449180, 10.1016/j.ygcen.2014.10.002.
54. Lassiter TL, Ryde IT, Levin ED, Seidler FJ, Slotkin TA. 2010. Neonatal exposure to parathion alters lipid metabolism in adulthood: interactions with dietary fat intake and implications for neurodevelopmental deficits. Brain Res Bull 81(1):85–91, PMID: 19615431, 10.1016/j.brainresbull.2009.07.002.
55. Li X, Pham HT, Janesick AS, Blumberg B. 2012. Triflumizole is an obesogen in mice that acts through peroxisome proliferator activated receptor gamma (PPARγ). Environ Health Perspect 120(12):1720–1726, PMID: 23086663, 10.1289/ehp.1205383.
56. Lu YF, Jin T, Xu Y, Zhang D, Wu Q, Zhang YK, et al. 2013. Sex differences in the circadian variation of cytochrome p450 genes and corresponding nuclear receptors in mouse liver. Chronobiol Int 30(9):1135–1143, PMID: 23926955, 10.3109/07420528.2013.805762.
57. Maglich JM, Stoltz CM, Goodwin B, Hawkins-Brown D, Moore JT, Kliewer SA. 2002. Nuclear pregnane x receptor and constitutive androstane receptor regulate overlapping but distinct sets of genes involved in xenobiotic detoxification. Mol Pharmacol 62(3):638–646, PMID: 12181440, 10.1124/mol.62.3.638.
58. Maqbool F, Mostafalou S, Bahadar H, Abdollahi M. 2016. Review of endocrine disorders associated with environmental toxicants and possible involved mechanisms. Life Sci 145:265–273, PMID: 26497928, 10.1016/j.lfs.2015.10.022.
59. Matic M, Bryzgalova G, Gao H, Antonson P, Humire P, Omoto Y, et al. 2013. Estrogen signalling and the metabolic syndrome: targeting the hepatic estrogen receptor alpha action. PLoS One 8(2):e57458, PMID: 23451233, 10.1371/journal.pone.0057458.
60. Montagner A, Polizzi A, Fouché E, Ducheix S, Lippi Y, Lasserre F, et al. 2016. Liver PPARα is crucial for whole-body fatty acid homeostasis and is protective against NAFLD. Gut 65(7):1202–1214, PMID: 26838599, 10.1136/gutjnl-2015-310798.
61. Mostafalou S, Abdollahi M. 2017. Pesticides: an update of human exposure and toxicity. Arch Toxicol 91(2):549–599, PMID: 27722929, 10.1007/s00204-016-1849-x.
62. Mulligan C, Kondakala S, Yang EJ, Stokes JV, Stewart JA, Kaplan BL, et al. 2017. Exposure to an environmentally relevant mixture of organochlorine compounds and polychlorinated biphenyls promotes hepatic steatosis in male Ob/Ob mice. Environ Toxicol 32(4):1399–1411, PMID: 27533883, 10.1002/tox.22334.
63. Newbold RR, Padilla-Banks E, Jefferson WN. 2009. Environmental estrogens and obesity. Mol Cell Endocrinol 304(1–2):84–89, PMID: 19433252, 10.1016/j.mce.2009.02.024.
64. Peris-Sampedro F, Cabré M, Basaure P, Reverte I, Domingo JL, Teresa Colomina M. 2015. Adulthood dietary exposure to a common pesticide leads to an obese-like phenotype and a diabetic profile in apoE3 mice. Environ Res 142:169–176, PMID: 26162960, 10.1016/j.envres.2015.06.036.
65. Pessayre D. 2007. Role of mitochondria in non-alcoholic fatty liver disease. J Gastroenterol Hepatol 22 (suppl 1):S20–S27, PMID: 17567459, 10.1111/j.1440-1746.2006.04640.x.
66. Polyzos SA, Kountouras J, Zavos C, Deretzi G. 2012. Nonalcoholic fatty liver disease: multimodal treatment options for a pathogenetically multiple-hit disease. J Clin Gastroenterol 46(4):272–284, 10.1097/MCG.0b013e31824587e0.
67. Qatanani M, Moore DD. 2005. CAR, the continuously advancing receptor, in drug metabolism and disease. Curr Drug Metab 6(4):329–339, PMID: 16101572, 10.2174/1389200054633899.
68. Régnier M, Polizzi A, Lippi Y, Fouché E, Michel G, Lukowicz C, et al. In press. Insights into the role of hepatocyte PPARα activity in response to fasting. Mol Cell Endocrinol, PMID: 28774777, 10.1016/j.mce.2017.07.035.
69. Riant E, Waget A, Cogo H, Arnal J-F, Burcelin R, Gourdy P. 2009. Estrogens protect against high-fat diet-induced insulin resistance and glucose intolerance in mice. Endocrinology 150(5):2109–2117, PMID: 19164473, 10.1210/en.2008-0971.
70. Rizzati V, Briand O, Guillou H, Gamet-Payrastre L. 2016. Effects of pesticide mixtures in human and animal models: an update of the recent literature. Chem Biol Interact 254:231–246, PMID: 27312199, 10.1016/j.cbi.2016.06.003.
71. Rosen MB, Das KP, Rooney J, Abbott B, Lau C, Corton JC. 2017. PPARα-independent transcriptional targets of perfluoroalkyl acids revealed by transcript profiling. Toxicology 387:95–107, PMID: 28558994, 10.1016/j.tox.2017.05.013.
72. Seidler FJ, Slotkin TA. 2011. Developmental neurotoxicity targeting hepatic and cardiac sympathetic innervation: effects of organophosphates are distinct from those of glucocorticoids. Brain Res Bull 85(3–4):225–230, PMID: 21453761, 10.1016/j.brainresbull.2011.03.021.
73. Shen P, Hsieh TH, Yue Y, Sun Q, Clark JM, Park Y. 2017. Deltamethrin increases the fat accumulation in 3T3-L1 adipocytes and Caenorhabditis elegans. Food Chem Toxicol 101:149–156, PMID: 28119079, 10.1016/j.fct.2017.01.015.
74. Smith CA, Want EJ, O’Maille G, Abagyan R, Siuzdak G. 2006. XCMS: processing mass spectrometry data for metabolite profiling using nonlinear peak alignment, matching, and identification. Anal Chem 78(3):779–787, PMID: 16448051, 10.1021/ac051437y.
75. Smyth GK. 2004. Linear Models and Empirical Bayes Methods for Assessing Differential Expression in Microarray Experiments. Stat Appl Genet Mol Biol 3(1):1–25, PMID: 16646809, 10.2202/1544-6115.1027.
76. Takeuchi S, Matsuda T, Kobayashi S, Takahashi T, Kojima H. 2006. In vitro screening of 200 pesticides for agonistic activity via mouse peroxisome proliferator-activated receptor (PPAR)α and PPARγ and quantitative analysis of in vivo induction pathway. Toxicol Appl Pharmacol 217(3):235–244, PMID: 17084873, 10.1016/j.taap.2006.08.011.
77. Tamura K, Inoue K, Takahashi M, Matsuo S, Irie K, Kodama Y, et al. 2013. Dose-response involvement of constitutive androstane receptor in mouse liver hypertrophy induced by triazole fungicides. Toxicol Lett 221(1):47–56, PMID: 23721867, 10.1016/j.toxlet.2013.05.011.
78. Tautenhahn R, Böttcher C, Neumann S. 2008. Highly sensitive feature detection for high resolution LC/MS. BMC Bioinformatics 9:504, PMID: 19040729, 10.1186/1471-2105-9-504.
79. Trygg J, Wold S. 2002. Orthogonal projections to latent structures (O-PLS). J Chemom 16(3):119–128. 10.1002/cem.695.
80. Upham J, Acott PD, O’Regan P, Sinal CJ, Crocker JF, Geldenhuys L, et al. 2007. The pesticide adjuvant, Toximul™, alters hepatic metabolism through effects on downstream targets of PPARα. Biochim Biophys Acta 1772(9):1057–1064, PMID: 17643967, 10.1016/j.bbadis.2007.06.003.
81. Velmurugan G, Ramprasath T, Swaminathan K, Mithieux G, Rajendhran J, Dhivakar M, et al. 2017. Gut microbial degradation of organophosphate insecticides-induces glucose intolerance via gluconeogenesis. Genome Biol 18(1):8, PMID: 28115022, 10.1186/s13059-016-1134-6.
82. 1 H NMR spectra for improved metabolic biomarker recovery. Anal Chem 81(1):56–66, PMID: 19049366, 10.1021/ac8011544.
83. Wahlang B, Falkner KC, Gregory B, Ansert D, Young D, Conklin DJ, et al. 2013. Polychlorinated biphenyl 153 is a diet-dependent obesogen that worsens nonalcoholic fatty liver disease in male C57BL6/J mice. J Nutr Biochem 24(9):1587–1595, PMID: 23618531, 10.1016/j.jnutbio.2013.01.009.
84. Wang TJ, Ngo D, Psychogios N, Dejam A, Larson MG, Vasan RS, et al. 2013. 2-Aminoadipic acid is a biomarker for diabetes risk. J Clin Invest 123(10):4309–4317, PMID: 24091325, 10.1172/JCI64801.
85. Wang P, Wang HP, Xu MY, Liang YJ, Sun YJ, Yang L, et al. 2014. Combined subchronic toxicity of dichlorvos with malathion or pirimicarb in mice liver and serum: a metabonomic study. Food Chem Toxicol 70:222–230, PMID: 24907623, 10.1016/j.fct.2014.05.027.
86. Wei P, Zhang J, Egan-Hafley M, Liang S, Moore DD. 2000. The nuclear receptor CAR mediates specific xenobiotic induction of drug metabolism. Nature 407(6806):920–923, PMID: 11057673, 10.1038/35038112.
87. Wikoff WR, Anfora AT, Liu J, Schultz PG, Lesley SA, Peters EC, et al. 2009. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc Natl Acad Sci USA 106(10):3698–3703, PMID: 19234110, 10.1073/pnas.0812874106.
88. Wu Y, Williams EG, Dubuis S, Mottis A, Jovaisaite V, Houten SM, et al. 2014. Multilayered genetic and omics dissection of mitochondrial activity in a mouse reference population. Cell 158(6):1415–1430, PMID: 25215496, 10.1016/j.cell.2014.07.039.
89. Yan S, Wang J, Dai J. 2015. Activation of sterol regulatory element-binding proteins in mice exposed to perfluorooctanoic acid for 28 days. Arch Toxicol 89(9):1569–1578, PMID: 25092180, 10.1007/s00204-014-1322-7.
90. Zhang S, Jin Y, Zeng Z, Liu Z, Fu Z. 2015. Subchronic exposure of mice to cadmium perturbs their hepatic energy metabolism and gut microbiome. Chem Res Toxicol 28(10):2000–2009, PMID: 26352046, 10.1021/acs.chemrestox.5b00237.
91. Zhu L, Brown WC, Cai Q, Krust A, Chambon P, McGuinness OP, et al. 2013. Estrogen treatment after ovariectomy protects against fatty liver and may improve pathway-selective insulin resistance. Diabetes 62(2):424–434, PMID: 22966069, 10.2337/db11-1718.
92. Zhu L, Martinez MN, Emfinger CH, Palmisano BT, Stafford JM. 2014. Estrogen signaling prevents diet-induced hepatic insulin resistance in male mice with obesity. Am J Physiol Endocrinol Metab 306(10):E1188–E1197, PMID: 24691030, 10.1152/ajpendo.00579.2013.