| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Journal of Lipid Research, Vol. 46, 123-134, January 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology
* Departments of Human Genetics, Medicine, Molecular Biology Institute, and Microbiology, Immunology, & Molecular Genetics, University of California, Los Angeles, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095
Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada T6G 2S2
Molecular Biology Institute, Howard Hughes Medical Institute, Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095
** Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706
1 To whom correspondence should be addressed. e-mail jlusis{at}mednet.ucla.edu
Through a positional cloning approach, the thioredoxin-interacting protein gene (Txnip) was recently identified as causal for a form of combined hyperlipidemia in mice (Bodnar, J. S., A. Chatterjee, L. W. Castellani, D. A. Ross, J. Ohmen, J. Cavalcoli, C. Wu, K. M. Dains, J. Catanese, M. Chu, S. S. Sheth, K. Charugundla, P. Demant, D. B. West, P. de Jong, and A. J. Lusis. 2002. Positional cloning of the combined hyperlipidemia gene Hyplip1. Nat. Genet. 30: 110–116). We now show that Txnip-deficient mice in the fed state exhibit a metabolic profile similar to fasted mice, including increased levels of plasma ketone bodies and free fatty acids, decreased glucose, and increased hepatic expression of peroxisome proliferator-activated receptor-
coactivator-1
, phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, and acyl-CoA oxidase. Dramatic differences in the expression of key metabolic enzymes were also observed in other tissues, and the fat-to-muscle ratio of Txnip-deficient mice was increased by 
40%. We demonstrate an effect of Txnip on the redox status, as the Txnip-deficient mice in the fed state had a significant increase in the ratio of NADH to NAD+. Surprisingly, we observed that Txnip-deficient mice and wild-type mice had similar levels of thioredoxin activity, suggesting that the effects of Txnip deficiency may be mediated in part by other interactions.
These results indicate a role for Txnip in the metabolic response to feeding and the maintenance of the redox status.
Abbreviations: AOX, acyl-CoA oxidase; ECL, enhanced chemiluminescence; Glut2, glucose transporter 2; G6Pase, glucose-6-phosphatase; KH, Krebs-Henseleit; MCAD, medium-chain acyl-CoA dehydrogenase; p-CREB, phosphorylated cAMP response element binding protein; PEPCK, phosphoenolpyruvate carboxykinase; PGC-1, peroxisome proliferator-activated receptor- coactivator-1; SCD1, stearoyl-CoA desaturase 1; SREBP-1c, sterol-response element binding protein-1c; TCA, tricarboxylic acid; TNF, tumor necrosis factor-; Txn, thioredoxin; Txnip, thioredoxin-interacting protein
Supplementary key words redox status • nutritional status • hypoglycemia • hypertriglyceridemia • fatty acid oxidation • mice
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Chen, S. T. Hui, F. M. Couto, I. N. Mungrue, D. B. Davis, A. D. Attie, A. J. Lusis, R. A. Davis, and A. Shalev Thioredoxin-interacting protein deficiency induces Akt/Bcl-xL signaling and pancreatic beta-cell mass and protects against diabetes FASEB J, October 1, 2008; 22(10): 3581 - 3594. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Chen, G. Saxena, I. N. Mungrue, A. J. Lusis, and A. Shalev Thioredoxin-Interacting Protein: A Critical Link Between Glucose Toxicity and {beta}-Cell Apoptosis Diabetes, April 1, 2008; 57(4): 938 - 944. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. A. Chutkow, P. Patwari, J. Yoshioka, and R. T. Lee Thioredoxin-interacting Protein (Txnip) Is a Critical Regulator of Hepatic Glucose Production J. Biol. Chem., January 25, 2008; 283(4): 2397 - 2406. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Reue and L. Vergnes Thematic review series: Systems Biology Approaches to Metabolic and Cardiovascular Disorders. Approaches to lipid metabolism gene identification and characterization in the postgenomic era J. Lipid Res., September 1, 2006; 47(9): 1891 - 1907. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Patwari, L. J. Higgins, W. A. Chutkow, J. Yoshioka, and R. T. Lee The Interaction of Thioredoxin with Txnip: EVIDENCE FOR FORMATION OF A MIXED DISULFIDE BY DISULFIDE EXCHANGE J. Biol. Chem., August 4, 2006; 281(31): 21884 - 21891. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Kolbe, A. Tiessen, H. Schluepmann, M. Paul, S. Ulrich, and P. Geigenberger Trehalose 6-phosphate regulates starch synthesis via posttranslational redox activation of ADP-glucose pyrophosphorylase PNAS, August 2, 2005; 102(31): 11118 - 11123. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Geigenberger, A. Kolbe, and A. Tiessen Redox regulation of carbon storage and partitioning in response to light and sugars J. Exp. Bot., June 1, 2005; 56(416): 1469 - 1479. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. H. Minn, C. Hafele, and A. Shalev Thioredoxin-Interacting Protein Is Stimulated by Glucose through a Carbohydrate Response Element and Induces {beta}-Cell Apoptosis Endocrinology, May 1, 2005; 146(5): 2397 - 2405. [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 |
