Almost 28% of Spanish children suffer from obesity. This figure makes it the most prevalent chronic disease in children and adolescents. Childhood obesity not only leads to health problems for the child, but also involves the risk of suffering from obesity and other related diseases during adulthood.

Both heredity and environment play crucial roles in the development of obesity, which is why it is defined as a complex disease. However, especially in cases of severe childhood obesity, genetics has an important role. Despite efforts in recent years, the genetic factors underlying the disease are still largely unknown. Now a team of scientists led by Pompeu Fabra University (UPF) and the Autonomous University of Madrid (UAM), has conducted a study on 480 Spanish children revealing new genes involved in severe childhood obesity.

“Most of the identified genetic variants associated with obesity have been inherited from a more moderately obese parent and probably have a dominant effect”, affirms  Luis Alberto Pérez Jurado, head of research and of the Genetics Unit at Pompeu Fabra University and of a group of the Centre for Biomedical Network Research on Rare Diseases (CIBERER) of the Carlos III Health Institute. “The combination of genetic load and the clearly “obesogenic” environment that has emerged in recent years in industrialized societies almost certainly explains the fact that the disease is expressed more evidently in children than in their parents”.

The hypothalamic regulation of appetite and hormonal function, keys to overweight

Several of the genes discovered have functions interrelated with the regulation of appetite, satiety and hormonal processes. GRIK1 and GRM7 are members of the family of glutamate receptors, which play various roles in the physiology of the central nervous system, one of them being to regulate energy balance and intake. According to Pérez Jurado, “in studies on mice it has been seen that the absence of another glutamate receptor of the same family (mGluR5) leads to a considerable decrease in weight”. GRPR is the gene that gives rise to the gastrin receptor, a hormone responsible for facilitating digestion in the stomach and promoting a feeling of satiety”. The malfunctioning of the GRPR gene can hinder the feeling of satiety and, consequently, lead to a greater intake of food”, says Pérez Jurado. In addition, the SLOC4C1 gene is involved, among other functions, in the transport of thyroid hormones. These hormones have been linked on numerous occasions with variations in weight, and hypothyroidism, for example, is a frequent cause of overweight.

Finally, the scientists have found a variation in the NPY gene in a family with multiple cases of severe obesity in at least three generations, where the men have attention deficit disorder and hyperactivity (ADHD). “The NPY gene gives rise to a peptide with modulator functions in the control of energy balance and behaviour, including feeding behaviour. For this reason, it is not surprising that there is a link between ADHD and obesity, since both can be caused by behavioural disorders regulated by the same gene”, comments Clara Serra, first author of the article and a researcher at Pompeu Fabra University and CIBERER.

“For the time being, obesity is one of the major public health problems in the Western world. It is therefore of vital importance that, in addition to promoting good habits, we study their genetic bases. Only in this way will we manage to get a better understanding of the mechanisms and the susceptibility of each person, and contribute to preventing or treating it and to curb the negative impact that the disease has on society”, Serra concludes.

Reference article: Clara Serra-Juhé, Gabriel Á. Martos-Moreno, Francesc Bou de Pieri, Raquel Flores, Juan R. González, Benjamín Rodríguez-Santiago, Jesús Argente, Luis A. Pérez-Jurado. Novel genes involved in severe early-onset obesity revealed by rare copy number and sequence variants. Plos Genetics. https://doi.org/10.1371/journal.pgen.1006657