This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow An author's correction has been published
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Harada, N.
Right arrow Articles by Kusunoki, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Harada, N.
Right arrow Articles by Kusunoki, J.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, March 2007, p. 1881-1888, Vol. 27, No. 5
0270-7306/07/$08.00+0     doi:10.1128/MCB.01122-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Hepatic De Novo Lipogenesis Is Present in Liver-Specific ACC1-Deficient Mice{triangledown} ,{dagger}

Naomoto Harada,1 Zenjun Oda,1 Yoshikazu Hara,2 Koji Fujinami,2 Mayumi Okawa,1 Katsuya Ohbuchi,2 Mari Yonemoto,2 Yuika Ikeda,2 Kenji Ohwaki,2 Katsumi Aragane,1 Yoshitaka Tamai,1 and Jun Kusunoki2*

Departments of Pharmacology,1 Metabolic Disorder Research, Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., 3 Okubo, Tsukuba, Ibaraki 300-2611, Japan2

Received 22 June 2006/ Returned for modification 3 October 2006/ Accepted 17 December 2006

Acetyl coenzyme A (acetyl-CoA) carboxylase (ACC) catalyzes carboxylation of acetyl-CoA to form malonyl-CoA. In mammals, two isozymes exist with distinct physiological roles: cytosolic ACC1 participates in de novo lipogenesis (DNL), and mitochondrial ACC2 is involved in negative regulation of mitochondrial ß-oxidation. Since systemic ACC1 null mice were embryonic lethal, to clarify the physiological role of ACC1 in hepatic DNL, we generated the liver-specific ACC1 null mouse by crossbreeding of an Acc1lox(ex46) mouse, in which exon 46 of Acc1 was flanked by two loxP sequences and the liver-specific Cre transgenic mouse. In liver-specific ACC1 null mice, neither hepatic Acc1 mRNA nor protein was detected. However, to compensate for ACC1 function, hepatic ACC2 protein and activity were induced 1.4 and 2.2 times, respectively. Surprisingly, hepatic DNL and malonyl-CoA were maintained at the same physiological levels as in wild-type mice. Furthermore, hepatic DNL was completely inhibited by an ACC1/2 dual inhibitor, 5-tetradecyloxyl-2-furancarboxylic acid. These results strongly demonstrate that malonyl-CoA from ACC2 can access fatty acid synthase and become the substrate for the DNL pathway under the unphysiological circumstances that result with ACC1 disruption. Therefore, there does not appear to be strict compartmentalization of malonyl-CoA from either of the ACC isozymes in the liver.

* Corresponding author. Mailing address: Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., 3 Okubo, Tsukuba, Ibaraki 300-2611, Japan. Phone: 81-29-877-2000. Fax: 81-29-877-2027. E-mail: jun_kusunoki{at}merck.com.

{triangledown} Published ahead of print on 6 January 2007.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, March 2007, p. 1881-1888, Vol. 27, No. 5
0270-7306/07/$08.00+0     doi:10.1128/MCB.01122-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Hou, T. Y., Ward, S. M., Murad, J. M., Watson, N. P., Israel, M. A., Duffield, G. E. (2009). ID2 (Inhibitor of DNA Binding 2) Is a Rhythmically Expressed Transcriptional Repressor Required for Circadian Clock Output in Mouse Liver. J. Biol. Chem. 284: 31735-31745 [Abstract] [Full Text]  
  • Steinberg, G. R., Kemp, B. E. (2009). AMPK in Health and Disease. Physiol. Rev. 89: 1025-1078 [Abstract] [Full Text]  
  • Gao, S., Kinzig, K. P., Aja, S., Scott, K. A., Keung, W., Kelly, S., Strynadka, K., Chohnan, S., Smith, W. W., Tamashiro, K. L. K., Ladenheim, E. E., Ronnett, G. V., Tu, Y., Birnbaum, M. J., Lopaschuk, G. D., Moran, T. H. (2007). From the Cover: Leptin activates hypothalamic acetyl-CoA carboxylase to inhibit food intake. Proc. Natl. Acad. Sci. USA 104: 17358-17363 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»