ChREBP downregulates SNAT2 amino acid transporter expression through interactions with SMRT in response to a high-carbohydrate diet
| Autor: | 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, Nimbe Torres |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
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 |
| Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 320:E102-E112 |
| ISSN: | 1522-1555 0193-1849 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|