HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 291/2/E358    most recent 00027.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (16) Citing Articles via Google Scholar Google Scholar Articles by Iizuka, K. Articles by Uyeda, K. Search for Related Content PubMed PubMed Citation Articles by Iizuka, K. Articles by Uyeda, K.

Deficiency of carbohydrate-activated transcription factor ChREBP prevents obesity and improves plasma glucose control in leptin-deficient (ob/ob) mice

Departments of ¹Biochemistry and ²Internal Medicine, University of Texas Southwestern Medical School; and ³Veterans Affairs Medical Center, Dallas, Texas

Submitted 19 January 2006 ; accepted in final form 13 March 2006

The transcription factor carbohydrate response element-binding protein (ChREBP) mediates insulin-independent, glucose-stimulated gene expression of multiple liver enzymes responsible for converting excess carbohydrate to fatty acids for long-term storage. To investigate ChREBP's role in the development of obesity and obesity-associated metabolic dysregulation, ChREBP-deficient mice were intercrossed with ob/ob mice. As a result of deficient leptin expression, ob/ob mice overeat, become obese and resistant to insulin, and display marked elevations in hepatic lipogenesis, gluconeogenesis, and plasma glucose and triglycerides. mRNA expression of all hepatic lipogenic enzymes was significantly lower in ob/ob-ChREBP^–/– than in ob/ob mice, resulting in decreased hepatic fatty acid synthesis and normalization of plasma free fatty acid and triglyceride levels. Overall weight gain in addition to adiposity was reduced in the doubly deficient mice. The former was largely attributable to decreased food intake and may result from decreased hypothalamic expression of the appetite-stimulating neuropeptide agouti-related protein. mRNA expression and activity of gluconeogenic enzymes also was lower in the doubly deficient mice, contributing to significantly lower blood glucose levels. The results of this study suggest that inactivation of ChREBP expression not only reduces fat synthesis and obesity in ob/ob mice but also results in improved glucose tolerance and appetite control.

carbohydrate response element-binding protein

This article has been cited by other articles:

				A. Perilhou, C. Tourrel-Cuzin, I. Kharroubi, C. Henique, V. Fauveau, T. Kitamura, C. Magnan, C. Postic, C. Prip-Buus, and M. Vasseur-Cognet The Transcription Factor COUP-TFII Is Negatively Regulated by Insulin and Glucose via Foxo1- and ChREBP-Controlled Pathways Mol. Cell. Biol., November 1, 2008; 28(21): 6568 - 6579. [Abstract] [Full Text] [PDF]