Impaired branched-chain amino acid metabolism may underlie the nonalcoholic fatty liver disease-like pathology of neonatal testosterone-treated female rats

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art_ANZAI_Impaired_branchedchain_amino_acid_metabolism_may_underlie_the_2017.PDF (4.4 MB)
Citações na Scopus
12
Tipo de produção
article
Data de publicação
2017
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
NATURE PUBLISHING GROUP
Autores
SIMOES, Manuel J.
PADMANABHAN, Vasantha
SILVA, Ismael D. C. G. da
Citação
SCIENTIFIC REPORTS, v.7, article ID 13167, 12p, 2017
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Polycystic ovary syndrome (PCOS) is frequently associated with non-alcoholic fatty liver disease (NAFLD), but the mechanisms involved in the development of NAFLD in PCOS are not well known. We investigated histological changes and metabolomic profile in the liver of rat models of PCOS phenotype induced by testosterone or estradiol. Two-day old female rats received sc injections of 1.25 mg testosterone propionate (Testos; n = 10), 0.5 mg estradiol benzoate (E2; n = 10), or vehicle (control group, CNT; n = 10). Animals were euthanized at 90-94 d of age and the liver was harvested for histological and metabolomic analyses. Findings showed only Testos group exhibited fatty liver morphology and higher levels of ketogenic and branched-chain amino acids (BCAA). Enrichment analysis showed effects of testosterone on BCAA degradation pathway and mitochondrial enzymes related to BCAA metabolism. Testos group also had a decreased liver fatty acid elongase 2 (ELOVL2) activity. E2 group had reduced lipid and acylcarnitine metabolites in the liver. Both groups had increased organic cation transporters (SLC22A4 and SLC16A9) activity. These findings indicate that neonatal testosterone treatment, but not estradiol, produces histological changes in female rat liver that mimic NAFLD with testosterone-treated rats showing impaired BCAA metabolism and dysfunctions in ELOVL2, SLC22A4 and SLC16A9 activity.
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URI
https://observatorio.fm.usp.br/handle/OPI/24303
Referências
  1. Alexanderson C, 2007, ENDOCRINOLOGY, V148, P5369, DOI 10.1210/en.2007-0305
  2. Alexanderson C, 2010, J STEROID BIOCHEM, V122, P82, DOI 10.1016/j.jsbmb.2009.10.006
  3. Alexanderson C, 2009, J ENDOCRINOL, V201, P49, DOI 10.1677/JOE-08-0534
  4. Byers SL, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0035538
  5. Bysani M, 2017, EPIGENOMICS-UK, V9, P105, DOI 10.2217/epi-2016-0087
  6. Caldwell ASL, 2014, ENDOCRINOLOGY, V155, P3146, DOI 10.1210/en.2014-1196
  7. Cheng SL, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0138889
  8. Cohen JC, 2011, SCIENCE, V332, P1519, DOI 10.1126/science.1204265
  9. Dongiovanni P., 2015, BIOMED RES INT, V2015, DOI 10.1155/2015/460190
  10. Draisma HHM, 2015, NAT COMMUN, V6, DOI 10.1038/ncomms8208
  11. Dumesic DA, 2015, ENDOCR REV, V36, P487, DOI 10.1210/er.2015-1018
  12. Gentric G, 2015, J CLIN INVEST, V125, P981, DOI 10.1172/JCI73957
  13. Grizzi F, 2007, MED HYPOTHESES, V69, P258, DOI 10.1016/j.mehy.2006.12.029
  14. Guidotti JE, 2003, J BIOL CHEM, V278, P19095, DOI 10.1074/jbc.M300982200
  15. Hogg K, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0024877
  16. Illig T, 2010, NAT GENET, V42, P137, DOI 10.1038/ng.507
  17. Imajo K, 2013, INT J MOL SCI, V14, P21833, DOI 10.3390/ijms141121833
  18. Jansen L, 2014, J HEPATOL, V61, P730, DOI 10.1016/j.jhep.2014.05.004
  19. Jones H, 2012, J CLIN ENDOCR METAB, V97, P3709, DOI 10.1210/jc.2012-1382
  20. Kaikkonen JE, 2017, HEPATOLOGY, V65, P491, DOI 10.1002/hep.28899
  21. Kanaya N, 2013, J STEROID BIOCHEM, V138, P100, DOI 10.1016/j.jsbmb.2013.04.001
  22. Kar Sujata, 2013, J Hum Reprod Sci, V6, P194, DOI 10.4103/0974-1208.121422
  23. Lazo M, 2015, CLIN GASTROENTEROL H, V13, P1686, DOI 10.1016/j.cgh.2014.12.033
  24. Lynch CJ, 2014, NAT REV ENDOCRINOL, V10, P723, DOI 10.1038/nrendo.2014.171
  25. Mahamed RR, 2011, FERTIL STERIL, V95, P1507, DOI 10.1016/j.fertnstert.2010.07.1093
  26. MARCONDES F. K., 2002, Braz. J. Biol., V62, P609, DOI 10.1590/S1519-69842002000400008
  27. Marcondes RR, 2015, GEN COMP ENDOCR, V212, P28, DOI 10.1016/j.ygcen.2015.01.006
  28. Marques RG, 2009, ACTA CIR BRAS, V24, P69, DOI 10.1590/S0102-86502009000100015
  29. Navarro LA, 2015, J HEPATOL, V62, P412, DOI 10.1016/j.jhep.2014.09.015
  30. Newgard CB, 2017, CELL METAB, V25, P43, DOI 10.1016/j.cmet.2016.09.018
  31. Newgard CB, 2009, CELL METAB, V9, P311, DOI 10.1016/j.cmet.2009.02.002
  32. Padmanabhan V, 2013, MOL CELL ENDOCRINOL, V373, P8, DOI 10.1016/j.mce.2012.10.005
  33. Patti GJ, 2012, NAT REV MOL CELL BIO, V13, P263, DOI 10.1038/nrm3314
  34. Pelis RM, 2014, CURR TOP MEMBR, V73, P233, DOI 10.1016/B978-0-12-800223-0.00006-2
  35. Roberts LD, 2013, CELL METAB, V18, P43, DOI 10.1016/j.cmet.2013.05.009
  36. Sarkar M., 2017, AM J GASTROENTEROL
  37. Shin SY, 2014, NAT GENET, V46, P543, DOI 10.1038/ng.2982
  38. Tikhonenko M, 2010, DIABETES, V59, P219, DOI 10.2337/db09-0728
  39. Vassilatou E, 2010, HUM REPROD, V25, P212, DOI 10.1093/humrep/dep380
  40. Walters KA, 2012, BIOL REPROD, V86, DOI 10.1095/biolreprod.111.097808
  41. Xia J., 2016, CURR PROTOC BIOINFOR, V55, DOI [10.1002/cpbi.11, DOI 10.1002/CPBI.11(2016).]
  42. Xita N, 2010, ANN NY ACAD SCI, V1205, P148, DOI 10.1111/j.1749-6632.2010.05658.x
  43. Xu WL, 2004, FASEB J, V18, P1746, DOI 10.1096/fj.04-2317fje
  44. Zhao Y, 2012, BMC MED, V10, DOI 10.1186/1741-7015-10-153

Coleções
Artigos e Materiais de Revistas Científicas - FM/MOG
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/58