Abstract
BHLHB2/DEC1 is a transcription factor implicated in cell proliferation, apoptosis, and metabolism, and is also known to play an important role in the regulation of the mammalian circadian rhythm. However, its precise role in metabolism remains unclear. We investigated the link between BHLHB2 and ChREBP, a glucose-activated transcription factor involved in the regulation of lipogenesis. Glucose stimulation and overexpression of dominant active ChREBP induced Bhlhb2 mRNA expression in rat hepatocytes. Deletion studies showed that ChoRE (-160 to -143bp) in the mouse Bhlhb2 promoter region is functional in vivo. Overexpression of BHLHB2 inhibited glucose and ChREBP-mediated induction of rat Fasn and liver pyruvate kinase (Lpk) mRNA. ChIP assay demonstrated that BHLHB2 bound to ChoRE in the Fasn, Lpk, and Bhlhb2 promoter regions in vivo. In conclusion, BHLHB2 and ChREBP constitute a novel feedback loop involved in the regulation of lipogenesis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / antagonists & inhibitors
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism*
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Basic Helix-Loop-Helix Transcription Factors / antagonists & inhibitors
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / metabolism*
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Feedback, Physiological*
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Gene Expression
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Glucose / metabolism*
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Glucose / pharmacology
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Hepatocytes / drug effects
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Hepatocytes / metabolism
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Homeodomain Proteins / antagonists & inhibitors
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism*
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Lipogenesis* / genetics
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Male
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Mice
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Promoter Regions, Genetic / drug effects
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Rats
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Rats, Wistar
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Transcriptional Activation
Substances
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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Basic Helix-Loop-Helix Transcription Factors
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Bhlhe40 protein, rat
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Homeodomain Proteins
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Mlxipl protein, rat
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Glucose