|
 |
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Journal of Lipid Research, Vol. 44, 356-368, February 2003
Copyright © 2003 by Lipid Research, Inc.
SREBP-1 integrates the actions of thyroid hormone, insulin, cAMP, and medium-chain fatty acids on ACC
transcription in hepatocytes
Department of Biochemistry and Molecular Pharmacology, School of Medicine, P.O. Box 9142, West Virginia University, Morgantown, WV
1 To whom correspondence should be addressed. e-mail: fbhillgartner{at}hsc.wvu.edu
In chick embryo hepatocytes, activation of acetyl-CoA carboxylase-
(ACC) transcription by 3,5,3'-triiodothyronine (T3) is mediated by a cis-acting regulatory unit (-101 to -71 bp) that binds the nuclear T3 receptor (TR) and sterol regulatory element-binding protein-1 (SREBP-1). SREBP-1 directly interacts with TR on the ACC gene to enhance T3-induced transcription. Here, we show that treating hepatocytes with T3 or insulin stimulates a 4-fold increase in the concentration of the mature, active form of SREBP-1. When T3 and insulin are added together, a 7-fold increase in the mature SREBP-1 concentration is observed. Time course studies indicate that the T3-induced increase in mature SREBP-1 abundance is closely associated with changes in ACC transcription and that the mechanism mediating the effect of T3 on mature SREBP-1 is distinct from that mediating the effect of insulin. Transfection analyses indicate that inhibition of ACC transcription by cAMP or hexanoate is mediated by ACC sequences between -101 and -71 bp. Treatment with cAMP or hexanoate suppresses the increase in mature SREBP-1 abundance caused by T3 and insulin.
These results establish a new interaction between the SREBP-1 and TR signaling pathways and provide evidence that SREBP-1 plays an active role in mediating the effects of T3, insulin, cAMP, and hexanoate on ACC transcription.
Abbreviations: ACC, acetyl-CoA carboxylase-; CAT, chloramphenicol acetyltransferase; CEH, chick embryo hepatocyte; ChREBP, carbohydrate response element binding protein; HNF-4, hepatocyte nuclear factor-4; LXR, liver X receptor; PUFA, polyunsaturated fatty acid; RXR, retinoid X receptor; SRE, sterol regulatory element; SREBP, sterol regulatory element binding protein; T3, 3,5,3'-triiodothyronine; T3RE, T3 response element; TK, thymidine kinase; TR, nuclear T3 receptor
Supplementary key words lipogenesis • hexanoate • nuclear T3 receptor • liver X receptor • chicken • fatty acid synthesis • liver • sterol regulatory element binding protein • adenosine 3',5'-cyclic monophosphate • acetyl-CoA carboxylase-
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Han, J. Wang, L. Li, Z. Zhang, L. Wang, and Z. Pan The role of insulin and glucose in goose primary hepatocyte triglyceride accumulation J. Exp. Biol., May 15, 2009; 212(10): 1553 - 1558. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kanayama, M. Arito, K. So, S. Hachimura, J. Inoue, and R. Sato Interaction between Sterol Regulatory Element-binding Proteins and Liver Receptor Homolog-1 Reciprocally Suppresses Their Transcriptional Activities J. Biol. Chem., April 6, 2007; 282(14): 10290 - 10298. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-Y. Liu, R. S. Heymann, F. Moatamed, J. J. Schultz, D. Sobel, and G. A. Brent A Mutant Thyroid Hormone Receptor {alpha} Antagonizes Peroxisome Proliferator-Activated Receptor {alpha} Signaling in Vivo and Impairs Fatty Acid Oxidation Endocrinology, March 1, 2007; 148(3): 1206 - 1217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Talukdar and F. B. Hillgartner The mechanism mediating the activation of acetyl-coenzyme A carboxylase-{alpha} gene transcription by the liver X receptor agonist T0-901317 J. Lipid Res., November 1, 2006; 47(11): 2451 - 2461. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Chu, M. Miyazaki, W. C. Man, and J. M. Ntambi Stearoyl-Coenzyme A Desaturase 1 Deficiency Protects against Hypertriglyceridemia and Increases Plasma High-Density Lipoprotein Cholesterol Induced by Liver X Receptor Activation Mol. Cell. Biol., September 15, 2006; 26(18): 6786 - 6798. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Hashimoto, M. Yamada, S. Matsumoto, T. Monden, T. Satoh, and M. Mori Mouse Sterol Response Element Binding Protein-1c Gene Expression Is Negatively Regulated by Thyroid Hormone Endocrinology, September 1, 2006; 147(9): 4292 - 4302. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Brewer, D. Lange, R. Baler, and A. Anzulovich SREBP-1 as a Transcriptional Integrator of Circadian and Nutritional Cues in the Liver J Biol Rhythms, June 1, 2005; 20(3): 195 - 205. [Abstract] [PDF]
|
|
|
|
 |
|
 Y. Zhang and F. B. Hillgartner Starvation and Feeding a High-Carbohydrate, Low-Fat Diet Regulate the Expression Sterol Regulatory Element-Binding Protein-1 in Chickens J. Nutr., September 1, 2004; 134(9): 2205 - 2210. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D.-J. Shin and T. F. Osborne Thyroid Hormone Regulation and Cholesterol Metabolism Are Connected through Sterol Regulatory Element-binding Protein-2 (SREBP-2) J. Biol. Chem., September 5, 2003; 278(36): 34114 - 34118. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Journal of Biological Chemistry |
| Molecular and Cellular Proteomics | ASBMB Today |