Modulation of carbohydrate response element-binding protein gene expression in 3T3-L1 adipocytes and rat adipose tissue.

Abstract

Carbohydrate response element-binding protein (ChREBP) is a rat homolog of human Williams-Beuren syndrome region 14 and a member of the basic helix-loop-helix leucine zipper transcription factor family. Its activation was found to be inducible by carbohydrate in the liver nuclear extracts from rats fed a high-sucrose diet. ChREBP is able to bind to the carbohydrate response element on the promoter of L-type pyruvate kinase and initiate the gene transcription. The detailed expression profile and transcriptional regulation of the ChREBP gene in adipocytes have not been characterized. In the present study, we provide evidence showing that 1) the ChREBP gene is expressed in differentiated 3T3-L1 adipocytes and rat adipose tissue; 2) insulin, glucose, and the antidiabetic agent troglitazone can significantly upregulate the gene expression of ChREBP in 3T3-L1 adipocytes, whereas free fatty acids suppress its expression in this cell type; 3) fasting followed by refeeding with a high-carbohydrate diet resulted in a 10-fold increase of ChREBP mRNA level in rat adipose tissue; and 4) ChREBP expression in adipose tissue is not significantly affected by the diabetic state. Taken together, the results we present are consistent with the idea that ChREBP is an important modulator of adipocyte biology and that its expression in adipose tissue is subject to combined regulation by glucose and insulin in vivo. The induction of ChREBP may serve as a novel pharmacological pathway for troglitazone-mediated hypoglycemic effects in vivo.

• Authors: Zhibin He, Tao Jiang, Zhuowei Wang, Moshe Levi, Jinping Li
• Journal: American journal of physiology. Endocrinology and metabolism (Am J Physiol Endocrinol Metab) Vol. 287 Issue 3 Pg. E424-30 (Sep 2004) ISSN: 0193-1849 [Print] United States
• PMID: 15100094 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
• Chromans
• DNA-Binding Proteins
• Fatty Acids, Nonesterified
• Hypoglycemic Agents
• Insulin
• Mlxipl protein, rat
• RNA, Messenger
• Thiazolidinediones
• Transcription Factors
• Troglitazone
• Glucose

Topics

• 3T3 Cells
• Adipocytes (cytology, drug effects, metabolism)
• Adipose Tissue (metabolism)
• Animals
• Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
• Cell Differentiation
• Chromans (pharmacology)
• DNA-Binding Proteins (genetics, metabolism)
• Diabetes Mellitus, Experimental (metabolism)
• Eating
• Fatty Acids, Nonesterified (pharmacology)
• Gene Expression (drug effects)
• Glucose (pharmacology)
• Hypoglycemic Agents (pharmacology)
• Insulin (pharmacology)
• Mice
• RNA, Messenger (metabolism)
• Rats
• Rats, Sprague-Dawley
• Stem Cells (cytology, metabolism)
• Thiazolidinediones (pharmacology)
• Transcription Factors (genetics, metabolism)
• Troglitazone