For some people, it is a daily battle to keep their weight down, with them struggling and failing to cut down the amount of food they eat. Many studies have shown these hunger pangs are regulated by the brain via sensory cues and peripheral physiological signals, however, the neural basis of this integration remains unclear. Now, a study from researchers at the University of Pennsylvania maps the biological mechanism behind the craving of hunger. The team states while the mere sight or smell of food can temporarily turn off neurons responsible for the drive to eat, their data shows the neurons only stay off if the brain receives a signal from the stomach after calories have been ingested. The opensource study is published in the journal Cell Reports.
Previous studies show the brain’s hypothalamus, known for controlling the sensation of hunger, is home to a population of neurons known as agouti-related protein-expressing neurons, or AgRP neurons. Recent studies from the lab showed these neurons are highly active when an animal is hungry, while their activity is suppressed only upon eating, smelling, or seeing food. Therefore, the group hypothesized these neurons functioned as a way for animals to avoid starvation. The current study distinguishes between the effects of seeing, smelling, and consuming food on reducing the activity of these AgRP neurons.
The current study worked with mice genetically engineered to allow the tracking of AgRP neuronal activity as the animals were presented food and/or fed. Results show nutrients are necessary for sustained reductions in AgRP neuron activity, with this dampening in activity proportional to the calories obtained. Data findings show this change in activity is recapitulated by the exogenous administration of gut-derived satiation signals.
The team states as they were confident the delivery of nutrients is delivering a signal to the brain, they wanted to ascertain how this signal was made possible. Results show giving mice hormones, such as cholecystokinin, peptide tyrosine, and amylin, all of which are normally secreted during digestion, led to dose-dependent decreases in AgRP neuronal activity. Data findings show when low doses of these three peptides were combined, they acted synergistically, leading to a robust decrease in AgRP neuron activity.
The team surmises their data shows the detection of nutrients by the central nervous system is critical for food intake control, controlling hunger cravings. For the future, the researchers state they now plan to further explore how these hormones suppress AgRP neuronal activity, perhaps looking for a way to trigger their release by mimicking the presence of nutrients in the gut.
Source: University of Pennsylvania
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