We have previously shown that angiotensin II (Ang II) increases the expression of the gene encoding adipocyte fatty acid synthase (FAS). Here we investigate the mechanism responsible for increased FAS gene transcription by Ang II. We demonstrate that Ang II increased luciferase activity by 3-fold in 3T3-L1 adipocytes transfected with fusion constructs linking the FAS promoter to the luciferase reporter gene. Interestingly, we mapped the Ang II regulatory sequences to the insulin-responsive region (E box) in the proximal FAS promoter. The E box alone was able to mediate Ang II responsiveness when linked to a heterologous promoter. However, this response was lost when mutations that abolished the binding of the E box to its transcription factors were introduced. Using adenoviral overexpression of a dominant-negative form of adipocyte determination and differentiation factor 1 (ADD1), a transcription factor that binds to the insulin-responsive E box, we demonstrated that ADD1 was required for Ang II regulation of the FAS gene in 3T3-L1 adipocytes. Furthermore, ADD1 expression was also up-regulated by Ang II. With the use of transfections as well as glucose transport assays, we further demonstrated that Ang II stimulation of the FAS gene was dependent on glucose. In conclusion, this is the first report that Ang II regulates adipocyte FAS gene transcription via insulin response sequences in a glucose-dependent manner and that this regulation is mediated at least in part via the ADD1 transcription factor.
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August 2001
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Research Article|
July 25 2001
Angiotensin II-responsive element is the insulin-responsive element in the adipocyte fatty acid synthase gene: role of adipocyte determination and differentiation factor 1/sterol-regulatory-element-binding protein 1c
Suyeon KIM;
Suyeon KIM
∗University of Tennessee, Nutrition Department and Agricultural Experiment Station, 1215 West Cumberland Avenue, Knoxville, TN 37996-1900, U.S.A.
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Isabelle DUGAIL;
Isabelle DUGAIL
†U465 INSERM, 15 rue de l'École de Médecine, 75270 Paris Cedex 06, France
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Melissa STANDRIDGE;
Melissa STANDRIDGE
∗University of Tennessee, Nutrition Department and Agricultural Experiment Station, 1215 West Cumberland Avenue, Knoxville, TN 37996-1900, U.S.A.
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Kate CLAYCOMBE;
Kate CLAYCOMBE
∗University of Tennessee, Nutrition Department and Agricultural Experiment Station, 1215 West Cumberland Avenue, Knoxville, TN 37996-1900, U.S.A.
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Joseph CHUN;
Joseph CHUN
‡University of Tennessee Medical Center, Division of Plastic Surgery, 1930 Alcoa Highway, Knoxville, TN 37920, U.S.A.
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Naïma MOUSTAÏD-MOUSSA
Naïma MOUSTAÏD-MOUSSA
1
∗University of Tennessee, Nutrition Department and Agricultural Experiment Station, 1215 West Cumberland Avenue, Knoxville, TN 37996-1900, U.S.A.
1To whom correspondence should be addressed (e-mail [email protected]).
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Publisher: Portland Press Ltd
Received:
December 14 2000
Revision Received:
April 19 2001
Accepted:
May 24 2001
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2001
2001
Biochem J (2001) 357 (3): 899–904.
Article history
Received:
December 14 2000
Revision Received:
April 19 2001
Accepted:
May 24 2001
Citation
Suyeon KIM, Isabelle DUGAIL, Melissa STANDRIDGE, Kate CLAYCOMBE, Joseph CHUN, Naïma MOUSTAÏD-MOUSSA; Angiotensin II-responsive element is the insulin-responsive element in the adipocyte fatty acid synthase gene: role of adipocyte determination and differentiation factor 1/sterol-regulatory-element-binding protein 1c. Biochem J 1 August 2001; 357 (3): 899–904. doi: https://doi.org/10.1042/bj3570899
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