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Article: Hepatic free fatty acids accumulate in experimental steatohepatitis: Role of adaptive pathways

TitleHepatic free fatty acids accumulate in experimental steatohepatitis: Role of adaptive pathways
Authors
KeywordsHepatic lipid synthesis
Lipid composition
Lipotoxicity
Non-alcoholic fatty liver disease
Saturated fatty acid
Issue Date2008
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jhep
Citation
Journal Of Hepatology, 2008, v. 48 n. 4, p. 638-647 How to Cite?
AbstractBackground/Aims: We determined the effects of dietary lipid composition on steatohepatitis development with particular attention to the nature of lipid molecules that accumulate in the liver and pathways of hepatic triglyceride synthesis. Methods: Mice were fed methionine and choline deficient (MCD) diets supplemented with 20% fat as lard (saturated) or olive oil (monounsaturated), for 3 weeks. Results: Irrespective of dietary lipid composition, MCD-fed mice developed steatosis, ballooning degeneration and lobular inflammation. MCD-feeding increased hepatic free fatty acid (FFA) levels 2-3-fold, as well as total triglyceride levels. Hepatic FFA composition was characterized by increased ratio of monounsaturated: saturated FFA. There were reduced nuclear levels of the lipogenic transcription factor sterol regulatory element binding protein-1 in MCD-fed mice, but no consistent reduction in fatty acid synthesis genes (acetyl-CoA carboxylase and fatty acid synthase). Consistent with pathways of hepatic triglyceride synthesis, expression of diacylglycerol acyltransferase-1 and -2 was increased, as were delta-5- and delta-6- fatty acid desaturase mRNA levels. Conclusions: In this nutritional model of steatohepatitis, accumulation of FFA occurs despite substantial suppression of lipogenesis and induction of triglyceride synthesis genes. Accumulation of FFA supports a lipotoxicity mechanism for liver injury in this form of fatty liver disease. © 2008 European Association for the Study of the Liver.
Persistent Identifierhttp://hdl.handle.net/10722/92515
ISSN
2015 Impact Factor: 10.59
2015 SCImago Journal Rankings: 4.570
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLarter, CZen_HK
dc.contributor.authorYeh, MMen_HK
dc.contributor.authorHaigh, WGen_HK
dc.contributor.authorWilliams, Jen_HK
dc.contributor.authorBrown, Sen_HK
dc.contributor.authorBellAnderson, KSen_HK
dc.contributor.authorLee, SPen_HK
dc.contributor.authorFarrell, GCen_HK
dc.date.accessioned2010-09-17T10:48:35Z-
dc.date.available2010-09-17T10:48:35Z-
dc.date.issued2008en_HK
dc.identifier.citationJournal Of Hepatology, 2008, v. 48 n. 4, p. 638-647en_HK
dc.identifier.issn0168-8278en_HK
dc.identifier.urihttp://hdl.handle.net/10722/92515-
dc.description.abstractBackground/Aims: We determined the effects of dietary lipid composition on steatohepatitis development with particular attention to the nature of lipid molecules that accumulate in the liver and pathways of hepatic triglyceride synthesis. Methods: Mice were fed methionine and choline deficient (MCD) diets supplemented with 20% fat as lard (saturated) or olive oil (monounsaturated), for 3 weeks. Results: Irrespective of dietary lipid composition, MCD-fed mice developed steatosis, ballooning degeneration and lobular inflammation. MCD-feeding increased hepatic free fatty acid (FFA) levels 2-3-fold, as well as total triglyceride levels. Hepatic FFA composition was characterized by increased ratio of monounsaturated: saturated FFA. There were reduced nuclear levels of the lipogenic transcription factor sterol regulatory element binding protein-1 in MCD-fed mice, but no consistent reduction in fatty acid synthesis genes (acetyl-CoA carboxylase and fatty acid synthase). Consistent with pathways of hepatic triglyceride synthesis, expression of diacylglycerol acyltransferase-1 and -2 was increased, as were delta-5- and delta-6- fatty acid desaturase mRNA levels. Conclusions: In this nutritional model of steatohepatitis, accumulation of FFA occurs despite substantial suppression of lipogenesis and induction of triglyceride synthesis genes. Accumulation of FFA supports a lipotoxicity mechanism for liver injury in this form of fatty liver disease. © 2008 European Association for the Study of the Liver.en_HK
dc.languageengen_HK
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jhepen_HK
dc.relation.ispartofJournal of Hepatologyen_HK
dc.subjectHepatic lipid synthesisen_HK
dc.subjectLipid compositionen_HK
dc.subjectLipotoxicityen_HK
dc.subjectNon-alcoholic fatty liver diseaseen_HK
dc.subjectSaturated fatty aciden_HK
dc.titleHepatic free fatty acids accumulate in experimental steatohepatitis: Role of adaptive pathwaysen_HK
dc.typeArticleen_HK
dc.identifier.emailLee, SP: sumlee@hku.hken_HK
dc.identifier.authorityLee, SP=rp01351en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.jhep.2007.12.011en_HK
dc.identifier.pmid18280001-
dc.identifier.scopuseid_2-s2.0-39849103404en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-39849103404&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume48en_HK
dc.identifier.issue4en_HK
dc.identifier.spage638en_HK
dc.identifier.epage647en_HK
dc.identifier.isiWOS:000255109000013-
dc.publisher.placeNetherlandsen_HK
dc.identifier.scopusauthoridLarter, CZ=11240153100en_HK
dc.identifier.scopusauthoridYeh, MM=8532307600en_HK
dc.identifier.scopusauthoridHaigh, WG=6603814152en_HK
dc.identifier.scopusauthoridWilliams, J=7409581386en_HK
dc.identifier.scopusauthoridBrown, S=54790506500en_HK
dc.identifier.scopusauthoridBellAnderson, KS=6506047834en_HK
dc.identifier.scopusauthoridLee, SP=7601417497en_HK
dc.identifier.scopusauthoridFarrell, GC=7102979833en_HK

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