Major finding on the tuberal nucleus broadens our understanding of the brain鈥檚 role in regulating metabolism and food intake, and offers a new avenue of research that can help combat obesity
Researchers at A*STAR鈥檚 Singapore Bioimaging Consortium (SBIC) have identified a new region of the mouse brain called the Tuberal Nucleus (TN), which affects appetite and body weight. It is notable that the TN is of a similar structure to the Nucleus Tuberalis Lateralis (NTL) in the human brain, of which the function is unknown.
Although not the first study in the world on neurons associated with controlling appetite, the roles of the mouse TN remained a mystery until now, and shows potential relevance to people.
This offers an understanding of appetite changes in humans, and potential treatment and prevention of eating disorders such as obesity. The findings were published in Science on 6 July 2018.
Past research has shown a strong correlation between neurodegenerative diseases and eating disorders. While neurodegenerative disease patients often show changes in appetite and metabolism, the neural mechanisms involved are not known. Specific pathological changes in NTL have been found in patients suffering from neurodegenerative diseases, but the functional consequence is unknown. The notion of NTL鈥檚 role in regulating food intake has never been tested either.
Dr Fu Yu and his research team from SBIC found that somatostatin (SST) neurons in TN played a crucial role in regulating feeding in healthy mice. In the team鈥檚 experiments, mice either fasted overnight, or were injected with ghrelin - a gut hormone which triggers hunger sensations. Results showed that these procedures led to a spike in SST neuron activity, indicating that these neurons were activated by hunger and likely involved in feeding regulation.
To validate the findings, the team used the methods of chemogenetics and optogenetics that acted as biological switches to precisely manipulate SST neuron activity in the TN of another group of mice.
These experiments demonstrated that activating SST neurons promoted food intake, suppressing SST neurons reduced food intake, and removal of SST neurons reduced body weight gain. The optogenetic experiment also showed that SST neurons could control various brain regions known to influence feeding regulation, such as the paraventricular nucleus (PVN), and bed nucleus of stria terminalis (BNST).
Moving forward, the team plans to study the genetic profile of SST neurons in TN and their impact on metabolic disregulations in neurodegenerative diseases. This could lead to new therapeutic targets for metabolic diseases.
Click here for the complete issue.