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Appetite regulation in the brain is complex, controlled by the effects of various neurotransmitters. While the appetite control pathways have been well-studied over the years, ongoing research describes the opposing messages in the brain impacting our relationship with food. One side tells us to eat, while the other tells us that we have eaten enough. Considering the opposing appetite pathways may have a significant impact on weight loss approaches and medications, helping to maintain weight loss and reduce medication side effects.
New research maps the areas of the brain responsible for cravings and hunger
New studies from Rutgers Health researchers give a new insight into the mechanisms in the brain involved in hunger and satiety. One study, led by Zhiping Pang, focused on a pathway of neurons that regulate satiety, the feeling that signals to us to stop eating. The other study, led by Mark Rossi, looked at a different neural pathway that triggers hunger.
Satiety pathway
In Pang’s study, the satiety pathway that was studied, involving neurons from the hypothalamus to the brainstem, includes many GLP-1 receptors. GLP-1 (glucagon-like peptide-1) is a naturally produced hormone that is released after eating to prompt the secretion of insulin, which lowers blood sugar. [1]
Drugs like semaglutide (which are used to treat diabetes and promote weight loss) are GLP-1 receptor agonists. They help reduce blood sugar levels and decrease appetite and cravings.
Pang’s study on mice shows that, when this satiety pathway is lit up, the mice stop eating, and when it is silenced or the receptors are deleted, the mice eat a lot. When the mice haven’t eaten for a while, the response signals in the pathway are weakened, reducing the satiety effect of GLP-1. In contrast, when they eat regularly and feel hungry in between, the response to GLP-1 is stronger. [1]
As such, when the pathway signals are kept consistently high, such as is the case with taking GLP-1 drugs like Ozempic, the feeling of satiety is maintained, meaning the individual rarely feels hungry. These drugs can prevent the natural rhythms and fluctuations of this pathway, which can contribute to weight regain upon drug discontinuation, as well as cause side effects, such as nausea, diarrhea, and constipation. [2]
Hunger pathway
Rossi’s pathway, including neurons from the stria terminalis to the lateral hypothalamus, functions in parallel yet with opposite effects. When these neural connections are triggered, mice suddenly become hungry and eat, whereas when the connections are blocked, the mice make no attempt to eat, regardless of the duration without food. [3]
Working in parallel
Various appetite pathways act on different parts of the brain, but they work in parallel to either release hunger signals (causing a desire to eat) or satiety signals (stopping the desire to eat). The strength of the neural signals in these pathways is also influenced in similar but opposing ways: [2]
- During a fasting period, the satiety pathway connections become weaker, while the hunger pathway connections become stronger.
- After eating, the satiety pathway connections become stronger, while the hunger pathway connections become weaker.
This means that both pathways require periods of satiety and hunger in order to have strong neural connections and hormone responses. Because of this, diets or medications that only impact one of these pathways have a limited duration of impact. [2]
Appetite vs. Cravings
Appetite refers to a general desire to eat, which can be caused by physical feelings of hunger. Cravings for food tend to be psychological and can be linked to certain neurotransmitters, food addictions, or other food-related disorders.
Unlike hunger and appetite, cravings are not due to the body’s necessary intake of food for energy and functioning. Often, cravings involve an intense desire for unhealthy foods, such as foods high in sugar, fat, or salt. These types of food impact dopamine levels, which are linked to the brain’s reward system and can contribute to the development of addiction or unhealthy or harmful behaviors. [4]
How these findings may benefit future GLP-1 drugs
These studies from Rutgers Health can influence the development of future GLP-1 receptor agonists and other weight management drugs that act on additional receptors. The findings indicate that allowing the body to rebalance hormones naturally, rather than removing neural responses or changing the ways hunger pathways function, can be a more sustainable way to manage hunger and cravings. [2]
For example, these scientists express interest in exploring the potential to create medications that provide short bursts of GLP-1, suggesting that this could help reduce appetite better over time than a constant release of GLP-1, which can help sustain weight loss and prevent certain side effects. [2]
These findings highlight a need to create drugs that target hunger and satiety pathways, rather than just one, as the two work in parallel. This might help maintain natural and synthetic hormone responses that become lessened over time with prolonged use of current GLP-1 medications.
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