Can the GLP-1 peptide help curb cravings? Keep reading to learn more.
In this article:
Round-up On the Latest GLP-1 Animal and Human Studies
Glucagon-like peptide 1 (GLP-1) is a gut-brain hormone. Scientists are interested in this special peptide because of its metabolic effects.
GLP-1 plays a vital role in metabolic functioning. It coordinates between certain prandial and postprandial functions including:
- Satiation - the point at which one feels full during a meal.
- Gastric emptying - the time it takes food to move from the stomach to the small intestine.
- Incretin effect - when blood sugar levels are lowered because insulin secretion is increased.
Because of its role in these processes, GLP-1 is a potential therapeutic agent for obesity and diabetes conditions. Different animal and human studies explore the underlying GLP-1 mechanisms that clarify its role in promoting obesity and how it can be used to help reduce eating.
There are a good number of preclinical studies that explore GLP-1 mechanisms in rodents. Here are some notable findings:
- GLP-1 is an internal signal for satiation. Meals initiate intestinal GLP-1 secretion and can induce satiation.
- When food is ingested, GLP-1 is released. Humoral or neuronal upper gut signals may trigger this release.
- There are two GLP-1 peaks during mealtime. Once upon initial ingestion and once again, when the food moves transitions into the distal bowel.
- Peripheral injections of physiological doses of GLP-1 help reduce meal size. This also does not induce avoidance.
- Exendin 9–39 (Ex-9) is a GLP-1 antagonist. When the appropriate doses of this are introduced at the right time, it can increase meal size.
- Vagal afferent neurons may mediate the effects of GLP-1 on eating. The initial findings suggest a paracrine mode of action rather than endocrine for intestinal GLP-.
- In lesion studies, satiation effects hinged on the expression of GLP-1 in vagal afferents.
- When there was a GLP-1 receptor (GLP-1R) knockdown in rats, satiation was delayed.
- GLP-1 interacts with vagal GLP-1R to decrease the size and duration of meals
- GLP-1 also increases the gastric emptying rate and glycemic excursion after meals.
- When GLP-1R vagal afferents are activated via optogenetics or chemogenetics, it reduces food intake without affecting other biological variables.
- Chronic GLP1 blockage can lead to weight gain and hyperphagia.
- Depleting GLP-1R in the central nervous system (CNS) does not impair gastric emptying or glucose metabolism. This suggests that intestinal GLP-1 plays a more significant role in triggering satiation rather than the CNS.
- Intestinal GLP-1 may also amplify the satiating effects of gastric distension.
- Satiating effects of GLP-1 and GLP-1R agonists decrease in obese rodents. Researchers believe that it may be due to lower levels of vagal afferent signaling.
Some of these findings don’t match with human studies. On top of the general species difference, computations of the appropriate GLP-1 levels are more difficult in rodents.
While there are more GLP-1 rodent studies, it’s also important to go over the human studies.
Here are the notable findings of GLP-1 in human samples:
- Lowering intestinal GLP-1 secretion can lead to a decrease in endogenous GLP-1R signaling.
- There is an inverse relationship between body mass index and GLP-1 incremental responses in meals.
- Meal-induced GLP-1 secretion is lower in obese and overweight individuals than lean individuals. Compared to individuals within the normal weight range, obese individuals show a 20% reduction in GLP-1 response to oral glucose. In addition, overweight individuals show a 10% reduction in GLP-1 response.
- Administering GLP-1 in obese individuals induces and prolongs the satiation effect.
- The incretin effect of GLP-1 is not seen in human studies.
- Unlike rodents, GLP-1 still has satiating effects on obese individuals.
- Peripheral injections of physiological doses of GLP-1 help reduce meal size. This also does not induce malaise and avoidance.
These human findings further confirm that GLP-1 is an endogenous satiation signal that requires mediation from vagal afferent neurons.
Implications on Pharmacological Treatments
All of these findings suggest that a decrease in endogenous GLP-1R activation contributes to hyperphagia and, in turn, contributes to obesity. Increasing the circulation of GLP-1 can activate GLP-1R in the CNS. Treatments that use GLP-1r agonists may help decrease food intake and may promote weight loss in obese individuals.
Understanding the role of this gut-brain hormone can broaden our understanding of weight gain and obesity. If you’re interested in learning more about how your epigenetic mechanisms can impact your health, visit Tru Diagnostic’s website today.