Five genes involved in salt sensitivity may be biomarkers and treatment targets for obesity, according to a study.
The study, “Unraveling the role of salt-sensitivity genes in obesity with integrated network biology and co-expression analysis,” was published in the journal PLOS One.
Obesity is caused by complex interactions between genetics and diet. Yet the specific mechanisms through which diet increases the risk of obesity in genetically susceptible people remain unknown.
Excessive salt intake plays a role in in the development and progression of metabolic diseases.
Salt sensitivity is a trait in which salt intake leads to an increase in blood pressure. However, whether gene expression (the process that leads to protein production) is altered in salt sensitivity genes (SSGs) in adipose, or fat, tissues is not well understood.
A group of researchers from Saudi Arabia set out to figure out the role of SSGs in the development of obesity.
Their study included 16 overweight (body mass index above 25 kg/m2) and 14 lean women.
Results indicated the presence of 2,691 genes with significantly different expression in adipose tissue of obese women compared with the controls.
Researchers then constructed a protein-interaction network of SSGs to evaluate relationships between the genes and help identify specific molecular pathways connected to obesity. This network was composed of 15,474 interactions among the SSGs with altered expression levels.
The scientists conducted a functional enrichment analysis, which helps determine the biological role of genes and their activity.
Overall, 125 obesity-related genes were enriched in adipose tissue, 24 of which were SSGs.
“These findings signifies the critical role of SSGs in … obesity,” the investigators wrote.
A co-expression analysis, which evaluates which genes are expressed together and likely to interact with each other to cause disease, revealed that 23 of these SSGs were co-expressed with enriched obesity-related genes. Eight of these SSGs had not been linked with obesity in prior genetic analysis.
The researchers identified five SSGs – ENPEP, WNK1, CYP3A5, SLC24A3 and CTSA – that were highly co-expressed with obesity-related genes and, as such, may be used as potential biomarkers or treatment target for obesity.
Collectively, these genes are implicated in processes such as blood pressure regulation, metabolism of molecules and therapies, and cellular balance of calcium.
“This study concludes that SSGs could act as molecular signatures for tracing the basis of adipogenesis [formation of fat cells] among obese patients,” the researchers wrote. “Integrated network-centered methods may accelerate the identification of new molecular targets.”
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