a potential target for future treatments. This discovery sheds light on the underlying factors contributing to childhood obesity and opens up new possibilities for developing effective therapies. The findings of this study, conducted by researchers from Children’s Hospital of Philadelphia (CHOP), could have significant implications for the treatment and prevention of childhood obesity.a druggable target for future therapeutic interventions. The findings were published today in the journal Cell Genomics.
Both environmental and genetic factors play critical roles in the increasing incidence of childhood obesity. While the exact role of genetics in childhood obesity is still not fully understood, prior studies show that neuronal pathways in the hypothalamus control food intake and are key regulators for the disease.
Prior international genome-wide association studies (GWAS) led by CHOP investigators found specific genetic markers, or loci, linked with obesity. Most of these studiThe recent study has discovered genetic sites linked to both childhood and adult obesity, with many of these sites located in regions of the genome that do not code for specific proteins, making it challenging to study their mechanisms. The study specifically focused on a genetic site called chr12q13, which contains the gene FAIM2 and showed a much stronger association with childhood obesity compared to adult obesity. The researchers were able to identify a specific variant associated with childhood obesity at this site, which is one of the strongest genetic signals implicated in childhood obesity.Dr. Sheridan H. Littleton, who worked on this project as part of the Center for Spatial and Functional Genomics team at CHOP, emphasized the potential for further research to uncover new treatments for childhood obesity targeting the specific actions of the variant. The locus under investigation has also been linked to other health issues such as increased risk of type 2 diabetes, higher body fat levels in both children and adults, and earlier onset of menstruation. The researchers employed different methods to analyze these connections.Researchers focused on rs7132908, a single nucleotide polymorphism (SNP), at the locus. Previous CHOP research connected the hypothalamus to appetite, which could be related to childhood obesity. The hypothalamus is deep inside the brain, making it difficult to study. To further study the effects of the rs7132908 variant, the researchers used stem cells that develop into hypothalamic neurons, a key cell type associated with eating behavior. The allele associated with obesity risk influenced the expression of the FAIM2 gene and decreased the proportion.The increase in neurons created as the stem cells changed indicates that the variant is linked to neurodevelopment. According to Struan F.A. Grant, PhD, Director of the Center for Spatial and Functional Genomics and the Daniel B. Burke Endowed Chair for Diabetes Research at CHOP, studies like this show how determination can uncover important information about previously unknown genetic variants and their role in various childhood and adult diseases. This research also emphasizes the significance of the brain in the genetics of obesity and offers a potential approach for dealing with it.The research was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development grants F31 HD105404 and R01 HD056465, the National Institute of Diabetes and Digestive and Kidney Diseases grant UM1 DK126194, and the Daniel B. Burke Endowed Chair for Diabetes Research.
