ChREBP downregulates SNAT2 amino acid transporter expression through interactions with SMRT in response to a high-carbohydrate diet.

ChREBP downregulates SNAT2 amino acid transporter expression through interactions with SMRT in response to a high-carbohydrate diet. Am J Physiol Endocrinol Metab. 2020 Nov 23;: Authors: Velázquez-Villegas L, Noriega LG, López-Barradas A, Tobon-Cornejo S, Méndez-García AL, Tovar AR, Torres N, Ortiz-Ortega VM Abstract 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 SNAT2 in response to a high-sucrose diet in rats by binding to a ChoRE site located -160 bp upstream of the transcriptional start site in the SNAT2 promoter region. Additionally, immunoprecipitation assays revealed that ChREBP and 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 ChIP 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. PMID: 33225719 [PubMed - as supp...
Source: Am J Physiol Endocri... - Category: Endocrinology Authors: Tags: Am J Physiol Endocrinol Metab Source Type: research