Obesity is a medical concern that increases a person’s risk of health problems and comorbidities such as heart disease, high blood pressure, diabetes, and cancers. Unhealthy behavioral practices such as physical inactivity and high caloric intake are widely considered significant culprits of excessive weight.
However, obesity is a heterogeneous and heritable disorder that results from environmental factors and genetic susceptibility, epigenetics, and metagenomics. For instance, DNA methylation in CpG islands plays an essential role in regulating gene expression in obesity-related genes and may relate to obesity risk in adolescents.
An earlier study concluded that aggregated changes of methylation levels in obesity-related genes are significantly associated with obesity in adolescents free of cardiometabolic disease manifestations.
In this study, researchers aimed to identify the relationship between the methylated regions in gene PON3 and the differential responsiveness of people with obesity to hypocaloric diet intervention.
Read the original publication of this study here: [ Differentially methylated regions (DMRs) in PON3 gene between responders and non-responders to a weight-loss dietary intervention: a new tool for precision management of obesity ]
Epigenetic marks such as DNA methylation could potentially be used as personalized biomarkers to predict whether specific weight-loss management and interventions might be effective.
Differentially methylated regions (DMRs) in PON3 gene between responders and non-responders to a weight-loss dietary intervention: a new tool for precision management of obesity
Researchers from the University of Navarra in Spain conducted a study to identify the Differentially methylated regions (DMR) that may determine the response to weight loss dietary intervention and its relations to metabolic variables.
DMRs are genomic locations with different methylation statuses among cells, tissues, and individual samples. These sites are regarded as possible functional regions involved in gene transcriptional regulation. Determining the DMRs among multiple tissues provides extensive information on epigenetic differences among human tissues.
Based on the change in body mass index (BMI), the researchers categorized 201 subjects with obesity and overweight into tertiles according to their response to a hypocaloric diet. Out of the total population, 64 were Responders (R), and 63 were Non-responders (NR).
The PON3 gene is a member of the paraoxonase family on chromosome 7, which encodes protein secreted into the bloodstream and is associated with high-density lipoprotein (HDL). In the baseline DNA methylation analysis, R and NR exhibited a DMR located at PON3 consisting of 13 CpG sites, in which eleven are significantly hypermethylated in R.
To analyze the implication of these 11 CpGs on weight loss, a z-score was performed to measure DMR methylation. This z-score negatively correlated with PON3 protein serum levels. This analysis showed a correlation between PON3 DNA methylation and BMI loss.
The total paraoxonase activity in serum, an enzyme associated with high-density lipoprotein, showed no significant difference between the groups, but PON enzymatic activity positively correlated with oxidized LDL levels.
This study identified a DMR within the PON3 gene related to PON3 protein levels in serum, and that could be used as a potential biomarker to predict the response to weight-loss dietary interventions.
In summary, the authors showed that the methylation status of a DMR at the PON3 gene was associated with study participants’ responsiveness to weight loss after a hypo-caloric diet. This suggests that PON3 might be a useful therapeutic target to reduce body weight. Results may help determine a more precise response to dietary and weight loss management interventions.
Takeaways:
- Obesity is a heterogeneous and heritable disorder, which results not only from environmental factors but also from genetic susceptibility, epigenetics, and metagenomics
- DNA methylation in obesity-related genes, such as PON3, may relate to obesity risk in adolescents.
- DMR within the PON3 gene is linked to PON3 protein levels in serum, and that could be used as a potential biomarker to predict the response to weight-loss dietary interventions.
- [ Differentially methylated regions (DMRs) in PON3 gene between responders and non-responders to a weight-loss dietary intervention: a new tool for precision management of obesity ]
- [ Genetic predictors of weight loss in overweight and obese subjects ]
- [ Association between DNA methylation in obesity-related genes and body mass index percentile in adolescents ]