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https://ir.library.oregonstate.edu/concern/articles/1v53jz76k

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  • Background: Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease and a risk factor for cirrhosis, hepatocellular carcinoma and liver failure. Previously, we reported that dietary docosahexaenoic acid (DHA, 22:6,n-3) was more effective than eicosapentaenoic acid (EPA, 20:5,n-3) at reversing western diet (WD) induced NASH in LDLR-/- mice. Methods: Using livers from our previous study, we carried out a global non-targeted metabolomic approach to quantify diet-induced changes in hepatic metabolism. Results: Livers from WD + olive oil (WD + O)-fed mice displayed histological and gene expression features consistent with NASH. The metabolomic analysis of 320 metabolites established that the WD and n-3 polyunsaturated fatty acid (PUFA) supplementation had broad effects on all major metabolic pathways. Livers from WD + O-fed mice were enriched in saturated (SFA) and monounsaturated fatty acids (MUFA), palmitoylsphingomyelin, cholesterol, n-6 PUFA, n-6 PUFA-containing phosphoglycerolipids, n-6 PUFA-derived oxidized lipids (12-HETE) and depleted of C20-22 n-3 PUFA-containing phosphoglycerolipids, C20-22 n-3 PUFA-derived oxidized lipids (18-HEPE, 17,18-DiHETE) and S-lactoylglutathione, a methylglyoxal detoxification product. WD + DHA was more effective than WD + EPA at attenuating WD + O-induced changes in NASH gene expression markers, n-6 PUFA and oxidized lipids, citrate and S-lactosyl glutathione. Diet-induced changes in hepatic MUFA and sphingolipid content were associated with changes in expression of enzymes involved in MUFA and sphingolipid synthesis. Changes in hepatic oxidized fatty acids and S-lactoylglutathione, however, correlated with hepatic n-3 and n-6 C20-22 PUFA content. Hepatic C20-22 n-3 PUFA content was inversely associated with hepatic α-tocopherol and ascorbate content and positively associated with urinary F2- and F3-isoprostanes, revealing diet effects on whole body oxidative stress. Conclusion: DHA regulation of hepatic SFA, MUFA, PUFA, sphingomyelin, PUFA-derived oxidized lipids and Slactoylglutathione may explain the protective effects of DHA against WD-induced NASH in LDLR-/- mice.
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  • description.provenance : Submitted by Erin Clark (erin.clark@oregonstate.edu) on 2014-04-16T22:33:31ZNo. of bitstreams: 3license_rdf: 1370 bytes, checksum: cd1af5ab51bcc7a5280cf305303530e9 (MD5)DepnerChristopherNutritionMetabolomicAnalysisOmega-3.pdf: 1741958 bytes, checksum: 38b3945e8b6ad8a3573d64e4231c4265 (MD5)DepnerChristopherNutritionMetabolomicAnalysisOmega-3_SupportingInformation.zip: 1504872 bytes, checksum: 95e70c9f5c4707bf7a9e795bb61bb508 (MD5)
  • description.provenance : Made available in DSpace on 2014-04-16T22:33:53Z (GMT). No. of bitstreams: 3license_rdf: 1370 bytes, checksum: cd1af5ab51bcc7a5280cf305303530e9 (MD5)DepnerChristopherNutritionMetabolomicAnalysisOmega-3.pdf: 1741958 bytes, checksum: 38b3945e8b6ad8a3573d64e4231c4265 (MD5)DepnerChristopherNutritionMetabolomicAnalysisOmega-3_SupportingInformation.zip: 1504872 bytes, checksum: 95e70c9f5c4707bf7a9e795bb61bb508 (MD5) Previous issue date: 2013-12-17
  • description.provenance : Approved for entry into archive by Erin Clark(erin.clark@oregonstate.edu) on 2014-04-16T22:33:53Z (GMT) No. of bitstreams: 3license_rdf: 1370 bytes, checksum: cd1af5ab51bcc7a5280cf305303530e9 (MD5)DepnerChristopherNutritionMetabolomicAnalysisOmega-3.pdf: 1741958 bytes, checksum: 38b3945e8b6ad8a3573d64e4231c4265 (MD5)DepnerChristopherNutritionMetabolomicAnalysisOmega-3_SupportingInformation.zip: 1504872 bytes, checksum: 95e70c9f5c4707bf7a9e795bb61bb508 (MD5)