Researchers have revealed insights into how the gene SH2B1 functions in the brain to regulate food intake.
Obesity is a complex condition influenced by various factors including genetics, environment, behavior, and more.
Throughout history, ensuring an adequate food supply was a challenge for survival and well-being. Nowadays, access to food is as easy as opening a refrigerator.
A gene known as SH2B1 has been identified as playing a crucial role in controlling food consumption.
Mutations in the SH2B1 gene in individuals are linked to obesity, type 2 diabetes, and metabolic dysfunction-related complications like steatotic liver disease.
Dr. Liangyou Rui from the U-M Medical School explains, “This gene manages eating habits and energy expenditure. Obesity stems from a delicate balance: Overeating leads to fat accumulation while insufficient energy expenditure results in fat buildup.”
Research by Rui and colleagues pinpointed the brain region where the gene operates, specifically the paraventricular hypothalamus (PVH), which is involved in regulating blood pressure and fluid levels.
Moreover, the research team found that neurons expressing SH2B1 form a network that communicates with downstream neurons in the dorsal raphe nucleus, situated in the brainstem.
The dorsal raphe nucleus is associated with energy equilibrium, weight control, and behavior driven by emotions.
Activating this neural network reduces appetite in mice. Conversely, suppressing SH2B1-expressing neurons in the PVH leads to obesity.
Additionally, the researchers unraveled the molecular process by which SH2B1 aids in weight maintenance, including enhancing BDNF/TrkB signaling. This signaling fosters brain growth during development and sustains brain health in adulthood. Disruption of this signaling pathway can lead to obesity and metabolic disorders.
Rui suggests that inflammation linked to weight gain may indirectly hinder this pathway, reducing the signals that indicate satiety.
Rui highlights, “The significance of SH2B1 activity is evident as it is highly conserved in various species, from fruit flies to humans. It serves as a fundamental player, boosting cell signaling and hormones like leptin and insulin that regulate appetite and metabolism.”
Furthermore, unlike current medications like Ozempic or Mounjaro that activate glp-1 receptors, there have been no identified adverse effects of enhancing SH2B protein.
Rui concludes, “By finding ways to boost SH2B activity, there is great potential for treating obesity and its associated conditions.”
