👤 L A Velázquez-Villegas

An increased number of low-density lipoprotein particles (LDL-P) is a common feature of patients with Metabolic syndrome (MetS). Increasing the size of these particles is one of the primary therapeutic and dietary interventions goals. However, genetic variability, like single nucleotide polymorphisms (SNPs), modulate the response to dietary strategies. Therefore, we hypothesise that the presence of SNPs in genes associated with MetS may modulate the effect of a dietary intervention on the size of LDL-P. This was a before-and-after clinical study conducted with 146 participants with MetS. The participants underwent a lifestyle intervention for 10 weeks. At baseline the presence of SNPs associated with MetS were determined. Anthropometric, biochemical, hormonal parameters, and lipoprotein analysis were taken before and after the intervention. Results revealed that the common homozygous ATP-binding cassette transporter A1 (ABCA1) genotype was associated with a decreased LDL-C concentration. However, after adjusting for sex, age and baseline weight, polymorphisms in the fat mass and obesity-associated (FTO) gene, the peroxisome proliferator-activated receptor (PPARγ), and the apolipoprotein E (APOE) gene were associated with a better response to the intervention in terms of increasing LDL-P size. Our results revealed changes in LDL-P size associated with polymorphisms in the APOE, FTO and PPARγ genes in response to the dietary intervention. These results highlight the importance of genetic factors in personalized nutritional strategies aimed at improving cardiovascular risk in patients with MetS. NCT03611140, www. gov. Show less

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. Show less