According to Science Daily, a collaboration of Baylor College of Medicine, the University of Cambridge, and the University of Exeter Medical School has uncovered a previously undiscovered gene that appears to be linked to obesity and antisocial behavior.
In human and animal models, uncommon mutations in the serotonin 2C receptor gene have been associated with increased susceptibility to obesity and behavioral problems. The results, which were published in Nature Medicine, will likely be used in clinical practice.
“Natural serotonin acts as a neurotransmitter, transmitting information from one section of the brain to another. Serotonin connects to serotonin receptors in brain cells to provide its message.
These brain cells are engaged in various processes, including mood, hunger, and social behavior management.” The study’s co-corresponding author was Dr. Yong Xu of the Baylor University Departments of Pediatrics-Nutrition and Molecular and Cell Biology.
The current study looked at the role of the serotonin 2C receptor in controlling body weight and related behaviors in collaboration with the Xu lab at the University of Cambridge and Dr. I. Sadaf Farooqi’s lab at the University of Oxford.
The team’s claim that the serotonin 2C receptor is a critical regulator of body weight and certain behaviors is backed by research from both the Xu and Farooqi labs, which have concentrated on fundamental and genetic animal studies, as well as human genetics.
The investigation began with the discovery that the serotonin 2C receptor gene was very variable among children with severe obesity. Scientists found 13 variations highly connected to being overweight using data from 19 people with no common ancestry. Following detailed characterization, 11 additional variations were discovered to cause receptor dysfunction.
Xu stated that loss-of-function variation carriers had hyperphagia or an insatiable hunger. They also had a penchant for some form of maladaptive behavior. ‘Emotional lability’ is described by Xu as “rapid, typically dramatic fluctuations in mood.
Animal models expressing one of the human loss-of-function variants in the serotonin 2C receptor gene became fat, validating the team’s hypothesis that loss-of-function mutations in this gene contribute to obesity.
Xu has underlined the diagnostic relevance of this result. Diagnostic gene panels for extreme pediatric obesity should include the serotonin 2C receptor gene. Furthermore, the researchers discovered a possible mechanism through which such mutations lead to weight increase and obesity. According to Xu, the serotonin 2C receptor is required for the regular firing of hypothalamic POMC neurons.
“Due to the disturbance in firing activity in the POMC neurons, animals with a loss-of-function mutation in this receptor are more likely to binge and gain weight. To prevent binge eating, the activity of these neurons must be normal.”
Using a mouse model, the researchers also investigated whether or not loss-of-function mutations altered mouse behavior. The altered mice, according to Xu, displayed less social behavior and more antagonism.
“These findings add to the scant data previously known for the relevance of the serotonin 2C receptor in sustaining socially acceptable conduct and inhibiting aggressive urges. We want to learn more about the methods employed.”
Setmelanotide and other drugs that act directly on downstream pathways may benefit people with obesity caused by this gene’s loss-of-function mutation. More research is needed to evaluate the effectiveness of this method.
