title: Time-dependent changes in lipid metabolism in mice with methionine choline deficiency-induced fatty liver disease.
abstract: Methionine and choline-deficient diet (MCD)-induced fatty liver is one of the best-studied animal models of fatty liver disease. The present study was performed to clarify the relative contributions of individual lipid metabolic pathways to the pathogenesis of MCD-induced fatty liver. Hepatic lipogenesis mediated by the sterol regulatory element-binding protein (SREBP-1c) was increased at 1 week, but not at 6 weeks, of MCD feeding. On the other hand, (14)C-palmitate oxidation did not change at 1 week, but significantly decreased at 6 weeks. This decrease was associated with increased expression of fatty acid translocase, a key enzyme involved in fatty acid uptake. Expression of endoplasmic reticulum stress markers was increased in mice given MCD for both 1 and 6 weeks. These findings suggest the presence of time-dependent differences in lipid metabolism in MCD-induced fatty liver disease: SREBP-1c-mediated lipogenesis is important in the early stages of fatty liver disease, whereas increased fatty acid uptake and decreased fatty acid oxidation become more important in the later stages.
authors.affiliation: Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul 138-736, Korea.
authors.forename: Han-Sol
authors.initials: HS
authors.lastname: Park
authors.forename: Byeong Hwan
authors.initials: BH
authors.lastname: Jeon
authors.forename: Sung Hoon
authors.initials: SH
authors.lastname: Woo
authors.forename: Jaechan
authors.initials: J
authors.lastname: Leem
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Jang
authors.forename: Min Sock
authors.initials: MS
authors.lastname: Cho
authors.forename: In-Sun
authors.initials: IS
authors.lastname: Park
authors.forename: Ki-Up
authors.initials: KU
authors.lastname: Lee
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Koh
mesh_terms: D000818:Animals; D002796:Choline Deficiency / Q000150:complications*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051048:Diacylglycerol O-Acyltransferase / Q000235:genetics / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism; D050612:Fatty Acid Transport Proteins / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism*; D005355:Fibrosis; D015870:Gene Expression; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000235:genetics / Q000378:metabolism; D008053:Lipid Mobilization / Q000235:genetics*; D050155:Lipogenesis / Q000235:genetics; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008715:Methionine / Q000172:deficiency*; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease; D010766:Phosphorylation; D000071701:Regulatory Factor X Transcription Factors; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C497250:Ddit3 protein, mouse; D015852:Eukaryotic Initiation Factor-2; D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids; C506120:Insig2 protein, mouse; D008565:Membrane Proteins; D000071701:Regulatory Factor X Transcription Factors; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D051742:Transcription Factor CHOP; D008715:Methionine; D005992:Glycerol-3-Phosphate O-Acyltransferase; C516957:DGAT2 protein, mouse; D051048:Diacylglycerol O-Acyltransferase; D064429:Fatty Acid Synthases
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