Most people have had the experience of being full, yet still eyeing the plate of fries sitting at the end of the table. As friends and families continue to chat around the dinner table after a three-course meal, hands continue to subconsciously reach out, time after time, for more food. But what physiological process actually takes place when someone becomes excessively full from food?
Recently a team of research scientists at the University of Michigan’s Molecular and Behavioral Neuroscience Institute (MBNI) were able to identify two classes of peptide-producing neurons that play opposing roles in the generation of feeding behaviors: anorexigenic neurons and orexigenic neurons.
Peptide-producing neurons are neurons that produce neuropeptides, which are short chains of peptides that can act as neurotransmitters.
Neuropeptides, on the other hand, are protein-like molecules that influence activity in the nervous system and act as signaling molecules to facilitate communication between neurons.
Huda Akil, research professor and co-director of MBNI, shared her team’s research approach in a recent press release.
“We used a transgenic approach to specifically address the POMC [pro-opiomelanocortin] neurons for optogenetic stimulation, and we expected to see a decrease in appetite. Instead, we saw a really remarkable effect,” Akil said.
Anorexigenic neurons express the gene POMC which inhibits feeding behavior. POMC is cleaved into several peptides such as alpha-melanocyte-stimulating hormones (α-MSH), a stress hormone known as adrenocorticotropic hormone and natural opioid β-endorphins.
When produced by neurons in the arcuate nucleus, α-MSH helps regulate eating behavior by blocking appetite.
β-endorphins, with their opioid analgesic properties of reducing pain, work alongside α-MSH to decrease feelings of “hunger” when POMC neurons are stimulated.
Orexigenic neurons, the other class of peptide-producing neurons, co-express genes that synthesize agouti-related peptide (AgRP) and neuropeptide Y (NPY) which act as appetite stimulators to enhance feelings of “hunger.”
Together POMC and AgRP neurons consolidate the numerous signals going through your body related to food intake, effectively controlling feeding behavior and maintaining homeostasis.
“POMC acts like a brake on feeding when it gets certain signals from the body, and AgRP acts like an accelerator pedal,” according to ScienceDaily.
But what happens when there are conflicting signals from the POMC and AgRP cells?
The close proximity of POMC and AgRP cells in the arcuate nucleus means that stimulation of one may inadvertently stimulate cells of the others residing close by.
“When both are stimulated at once, AgRP steals the show,” Akil said, according to ScienceDaily.
In research done on mice, when POMC and AgRP sent opposing signals that affect feeding behavior, AgRP ultimately won, leading to a significantly noticeable increase in appetite.
Akil’s team then continued to follow the downstream pathway starting from POMC and AgRP activation.
In doing so, they were able to find that activation of AgRP and POMC triggered the release of the opioid β-endorphins. However, upon administering naloxone — an opioid antagonist that reverses the effects of opioid medication — the “hunger” in the mice decreased, and their feeding behavior stopped.
“This suggests that the brain’s own endogenous opioid system may play a role in wanting to eat beyond what is needed,” Akil said. “Our work shows that the signals of satiety — of having had enough food — are not powerful enough to work against the strong drive to eat, which has strong evolutionary value.”
Akil and several other researchers are looking into the potential use of opioid antagonists as a potential method in addressing the global epidemic of obesity. Meanwhile, Akil hopes to unravel the underlying metabolic and psychological mechanisms that drive feeding behavior.
