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Fatty acid elongase-5 (Elovl5) regulates hepatic triglyceride catabolism in obese C57BL/6J mice Public Deposited

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  • Nonalcoholic fatty liver disease is a major public health concern in the obese and type 2 diabetic populations. The high-fat lard diet induces obesity and fatty liver in C57BL/6J mice and suppresses expression of the PPAR-target gene, FA elongase 5 (Elovl5). Elovl5 plays a key role in MUFA and PUFA synthesis. Increasing hepatic Elovl5 activity in obese mice lowered hepatic TGs and endoplasmic reticulum stress markers (X-box binding protein 1 and cAMP-dependent transcription factor 6α) and increased TG catabolism and fatty acyl carnitines. Increased hepatic Elovl5 activity did not increase hepatic capacity for β-oxidation. Elovl5 effects on hepatic TG catabolism were linked to increased protein levels of adipocyte TG lipase (ATGL) and comparative gene identification 58 (CGI58). Elevated hepatic Elovl5 activity also induced the expression of some (pyruvate dehydrogenase kinase 4 and fibroblast growth factor 21), but not other cytochrome P450 4A10 (CYP4A10), PPAR-target genes. FA products of Elovl5 activity increased ATGL, but not CGI58, mRNA through PPARβ-dependent mechanisms in human HepG2 cells. Treatment of mouse AML12 hepatocytes with the PPARβ agonist (GW0742) decreased (14)C-18:2,n-6 in TGs but did not affect β-oxidation. These studies establish that Elovl5 activity regulates hepatic levels of FAs controlling PPARβ activity, ATGL expression, and TG catabolism, but not FA oxidation.
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  • Tripathy, S., Lytle, K. A., Stevens, R. D., Bain, J. R., Newgard, C. B., Greenberg, A. S., ... & Jump, D. B. (2014). Fatty acid elongase-5 (Elovl5) regulates hepatic triglyceride catabolism in obese C57BL/6J mice. Journal of Lipid Research, 55(7), 1448-1464. doi:10.1194/jlr.M050062
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  • 55
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  • 7
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  • This work was supported the USDA National Institute of Food and AgricultureGrant 2009-65200-05846 and the National Institutes of Health GrantsDK043220 (D.B.J.), DK094600 (D.B.J.), and AA020561 (L-S.H.).
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  • description.provenance : Made available in DSpace on 2014-07-28T19:14:21Z (GMT). No. of bitstreams: 2TripathySasmitaBPHSFattyAcidElongase.pdf: 2010920 bytes, checksum: dceaddabf54e248ec81981db84035ae7 (MD5)TripathySasmitaBPHSFattyAcidElongase_SupplementalData.pdf: 270033 bytes, checksum: e278e23d8b47a554088c23a63c8511e5 (MD5) Previous issue date: 2014-05-09
  • description.provenance : Submitted by Erin Clark (erin.clark@oregonstate.edu) on 2014-07-28T19:13:45ZNo. of bitstreams: 2TripathySasmitaBPHSFattyAcidElongase.pdf: 2010920 bytes, checksum: dceaddabf54e248ec81981db84035ae7 (MD5)TripathySasmitaBPHSFattyAcidElongase_SupplementalData.pdf: 270033 bytes, checksum: e278e23d8b47a554088c23a63c8511e5 (MD5)
  • description.provenance : Approved for entry into archive by Erin Clark(erin.clark@oregonstate.edu) on 2014-07-28T19:14:21Z (GMT) No. of bitstreams: 2TripathySasmitaBPHSFattyAcidElongase.pdf: 2010920 bytes, checksum: dceaddabf54e248ec81981db84035ae7 (MD5)TripathySasmitaBPHSFattyAcidElongase_SupplementalData.pdf: 270033 bytes, checksum: e278e23d8b47a554088c23a63c8511e5 (MD5)

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TripathySasmitaPHHSFattyAcidElongase_SupplementalData.pdf 07/26/2017 Public