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

• Published in: American journal of physiology: endocrinology and metabolism 2004-09, Vol.287 (3), p.E424-E430
• Main Authors: He, Zhibin, Jiang, Tao, Wang, Zhuowei, Levi, Moshe, Li, Jinping
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Adipocytes - cytology; Adipocytes - drug effects; Adipocytes - metabolism; Adipose Tissue - metabolism; Animals; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Cell Differentiation; Chromans - pharmacology; Diabetes Mellitus, Experimental - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Eating; Fatty Acids, Nonesterified - pharmacology; Gene Expression - drug effects; Glucose - pharmacology; Hypoglycemic Agents - pharmacology; Insulin - pharmacology; Mice; Rats; Rats, Sprague-Dawley; RNA, Messenger - metabolism; Stem Cells - cytology; Stem Cells - metabolism; Thiazolidinediones - pharmacology; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00568.2003

1 Division of Renal Diseases and Hypertension, Department of Medicine, and 2 Department of Physiology and Biophysics, University of Colorado Health Science Center, Denver, Colorado 80262 Submitted 12 December 2003 ; accepted in final form 10 April 2004 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. adipogenesis; lipogenesis Address for reprint requests and other correspondence: J. Li, 4200 East 9th Ave., C281, Denver, CO 80262 (E-mail: jinping.li{at}uchsc.edu ).