Endotoxin, zymosan, and cytokines decrease the expression of the transcription factor, carbohydrate response element binding protein, and its target genes.

Abstract

Carbohydrate response element binding protein (ChREBP) is a recently discovered transcription factor whose levels and activity are increased by glucose leading to the activation of target genes, which include acetyl-CoA carboxylase, fatty acid synthase, and liver-type pyruvate kinase. Here, we demonstrate that lipopolysaccharide (LPS) treatment causes a marked decrease in ChREBP mRNA and protein levels in the liver of mice fed a normal chow diet or in mice fasted for 24 h and then re-fed a high carbohydrate diet. This decrease occurs rapidly and is a sensitive response (half-maximal dose 0.1 μg/mouse). The decrease in ChREBP is accompanied by a decrease in the expression of ChREBP target genes. Zymosan and turpentine treatment also decrease hepatic ChREBP levels and the expression of its target genes. Additionally, tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) decrease liver ChREBP expression both in vivo and in Hep3B cells in culture. Finally, LPS decreased ChREBP expression in muscle and adipose tissue. These studies demonstrate that ChREBP is down-regulated during the acute phase response resulting in alterations in the expression of ChREBP regulated target genes. Thus, ChREBP joins a growing list of transcription factors that are regulated during the acute phase response.

• Authors: Kenneth R Feingold, Judy K Shigenaga, Sophie M Patzek, Lisa G Chui, Arthur Moser, Carl Grunfeld
• Journal: Innate immunity (Innate Immun) Vol. 17 Issue 2 Pg. 174-82 (Apr 2011) ISSN: 1753-4267 [Electronic] United States
• PMID: 20100709 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
• Dietary Carbohydrates
• Endotoxins
• Interleukin-1beta
• Lipopolysaccharides
• Mlxipl protein, mouse
• Nuclear Proteins
• Transcription Factors
• Tumor Necrosis Factor-alpha
• Zymosan
• Acetyl-CoA Carboxylase
• Turpentine

Topics

• Acetyl-CoA Carboxylase (metabolism)
• Animals
• Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
• Cell Line
• Dietary Carbohydrates (administration & dosage)
• Endotoxins (immunology, metabolism)
• Gene Expression Regulation (drug effects, immunology)
• Interleukin-1beta (immunology, metabolism)
• Lipopolysaccharides (pharmacology)
• Liver (drug effects, metabolism)
• Mice
• Mice, Inbred C57BL
• Nuclear Proteins (genetics, immunology, metabolism)
• Transcription Factors (genetics, immunology, metabolism)
• Tumor Necrosis Factor-alpha (immunology, metabolism)
• Turpentine (metabolism)
• Zymosan (immunology, metabolism)