1. ChREBP downregulates SNAT2 amino acid transporter expression through interactions with SMRT in response to a high-carbohydrate diet
- Author
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Ana Luisa Mendez-Garcia, Victor Manuel Ortiz-Ortega, Laura A. Velázquez-Villegas, Adriana M. López-Barradas, Lilia G. Noriega, Sandra Tobon-Cornejo, Armando R. Tovar, and Nimbe Torres
- Subjects
Blood Glucose ,Male ,0301 basic medicine ,Chromatin Immunoprecipitation ,Sucrose ,medicine.medical_specialty ,Amino Acid Transport System A ,Transcription, Genetic ,Physiology ,Endocrinology, Diabetes and Metabolism ,Primary Cell Culture ,Down-Regulation ,High carbohydrate diet ,03 medical and health sciences ,0302 clinical medicine ,Physiology (medical) ,Internal medicine ,Dietary Carbohydrates ,medicine ,Animals ,Nuclear Receptor Co-Repressor 2 ,Amino acid metabolism ,Amino acid transporter ,Rats, Wistar ,Carbohydrate-responsive element-binding protein ,Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ,Chemistry ,Carbohydrate ,Diet ,Rats ,030104 developmental biology ,Endocrinology ,Biochemistry ,Hepatocytes ,030217 neurology & neurosurgery - Abstract
Carbohydrate responsive element-binding protein (ChREBP) has been identified as a primary transcription factor that maintains energy homeostasis through transcriptional regulation of glycolytic, lipogenic, and gluconeogenic enzymes in response to a high-carbohydrate diet. Amino acids are important substrates for gluconeogenesis, but nevertheless, knowledge is lacking about whether this transcription factor regulates genes involved in the transport or use of these metabolites. Here, we demonstrate that ChREBP represses the expression of the amino acid transporter sodium-coupled neutral amino acid transporter 2 (SNAT2) in response to a high-sucrose diet in rats by binding to a carbohydrate response element (ChoRE) site located -160 bp upstream of the transcriptional start site in the SNAT2 promoter region. Additionally, immunoprecipitation assays revealed that ChREBP and silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) interact with each other, as part of the complex that repress SNAT2 expression. The interaction between these proteins was confirmed by an in vivo chromatin immunoprecipitation assay. These findings suggest that glucogenic amino acid uptake by the liver is controlled by ChREBP through the repression of SNAT2 expression in rats consuming a high-carbohydrate diet.
- Published
- 2021
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