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Mol. Cells 2011; 32(6): 571-577

Published online December 31, 2011

https://doi.org/10.1007/s10059-011-0184-6

© The Korean Society for Molecular and Cellular Biology

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

Han-Sol Park1,4, Byeong Hwan Jeon1,4, Sung Hoon Woo1, Jaechan Leem2, Jung Eun Jang2, Min Sock Cho3, In-Sun Park3, Ki-Up Lee2, and Eun Hee Koh2,*

1Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul 138-736, Korea, 2Department of Internal Medicine, University of Ulsan College of Medicine, Seoul 138-736, Korea, 3Department of Anatomy, College of Medicine, Inha University, Incheon 401-103, Korea, 4These authors contributed equally to this work.

Correspondence to : *Correspondence: ehk@amc.seoul.kr

Received: September 2, 2011; Revised: October 10, 2011; Accepted: October 11, 2011

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, 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.

Keywords endoplasmic reticulum stress, fatty acid oxidation, lipogenesis, non-alcholic fatty liver disease, sterol regulatory element binding protein-1c

Article

Research Article

Mol. Cells 2011; 32(6): 571-577

Published online December 31, 2011 https://doi.org/10.1007/s10059-011-0184-6

Copyright © The Korean Society for Molecular and Cellular Biology.

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

Han-Sol Park1,4, Byeong Hwan Jeon1,4, Sung Hoon Woo1, Jaechan Leem2, Jung Eun Jang2, Min Sock Cho3, In-Sun Park3, Ki-Up Lee2, and Eun Hee Koh2,*

1Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul 138-736, Korea, 2Department of Internal Medicine, University of Ulsan College of Medicine, Seoul 138-736, Korea, 3Department of Anatomy, College of Medicine, Inha University, Incheon 401-103, Korea, 4These authors contributed equally to this work.

Correspondence to:*Correspondence: ehk@amc.seoul.kr

Received: September 2, 2011; Revised: October 10, 2011; Accepted: October 11, 2011

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, 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.

Keywords: endoplasmic reticulum stress, fatty acid oxidation, lipogenesis, non-alcholic fatty liver disease, sterol regulatory element binding protein-1c

Mol. Cells
May 31, 2022 Vol.45 No.5, pp. 273~352
COVER PICTURE
Fe2+ ion depletion-induced expression of BΔGFP at the early stage of leaf development (Choi et al., pp. 294-305).

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