Time-Dependent Changes in Lipid Metabolism in Mice with Methionine Choline Deficiency-Induced Fatty Liver Disease

• Published in: Molecules and cells Vol. 32; no. 6; pp. 571 - 577
• Main Authors: Park, H.S., Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea, Jeon, B.H., Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea, Woo, S.H., Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea, Leem, J.C., University of Ulsan College of Medicine, Seoul, Republic of Korea, Jang, J.E., University of Ulsan College of Medicine, Seoul, Republic of Korea, Cho, M.S., Inha University, Incheon, Republic of Korea, Park, I.S., Inha University, Incheon, Republic of Korea, Lee, K.U., University of Ulsan College of Medicine, Seoul, Republic of Korea, Koh, E.H., University of Ulsan College of Medicine, Seoul, Republic of Korea
• Format: Journal Article
• Language: English
• Published: Springer Korean Society for Molecular and Cellular Biology 01-12-2011; 한국분자세포생물학회
• Subjects: Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Cell Biology; Choline Deficiency - complications; Diacylglycerol O-Acyltransferase - genetics; Diacylglycerol O-Acyltransferase - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Endoplasmic Reticulum Stress; Eukaryotic Initiation Factor-2 - metabolism; fatty acid oxidation; Fatty Acid Synthases - genetics; Fatty Acid Synthases - metabolism; Fatty Acid Transport Proteins - genetics; Fatty Acid Transport Proteins - metabolism; Fatty Acids - metabolism; Fatty Liver - etiology; Fatty Liver - metabolism; Fibrosis; Gene Expression; Glycerol-3-Phosphate O-Acyltransferase - genetics; Glycerol-3-Phosphate O-Acyltransferase - metabolism; Life Sciences; Lipid Mobilization - genetics; LIPOGENESE; LIPOGENESIS; Lipogenesis - genetics; Liver - metabolism; Liver - pathology; Membrane Proteins - genetics; Membrane Proteins - metabolism; Methionine - deficiency; Mice; Mice, Inbred C57BL; non-alcholic fatty liver disease; Non-alcoholic Fatty Liver Disease; Phosphorylation; Regulatory Factor X Transcription Factors; Sterol Regulatory Element Binding Protein 1 - genetics; Sterol Regulatory Element Binding Protein 1 - metabolism; sterol regulatory element binding protein-1c; Transcription Factor CHOP - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism; 생물학; sterol regulatory element binding protein-1c; lipogenesis; non-alcholic fatty liver disease; fatty acid oxidation; endoplasmic reticulum stress
• ISSN: 1016-8478; 0219-1032
• DOI: 10.1007/s10059-011-0184-6

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, ∨14C-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.