Blocking CB1 receptors in the stomach triggers release of a satiety hormone through a specific cellular pathway
CB1 receptor blockade stimulated gastric production and release of nesfatin-1, a hormone that promotes satiety, through the mTOR/S6k signaling pathway, revealing how the peripheral cannabinoid system regulates food intake via the stomach.
Quick Facts
What This Study Found
When rats were treated with the CB1 inverse agonist rimonabant, food intake decreased and gastric secretion of Nucb2/nesfatin-1 (a satiety peptide) increased. Circulating nesfatin-1 levels in the blood also rose.
Rimonabant activated the mTOR signaling pathway in the stomach, as shown by increased phosphorylated mTOR. When mTOR was blocked with rapamycin, rimonabant could no longer stimulate nesfatin-1 release, confirming that the mTOR/S6k pathway mediates this effect.
The same results were confirmed using a second CB1 antagonist (AM281), strengthening the conclusion that this is specifically a CB1-mediated mechanism.
Key Numbers
Rimonabant increased gastric nesfatin-1 secretion and circulating levels. Rapamycin blocked rimonabant's effect on nesfatin-1 release. mTOR phosphorylation increased in gastric tissue after CB1 blockade. Confirmed with second CB1 antagonist AM281.
How They Did This
Rats received rimonabant, rapamycin, rapamycin plus rimonabant, or vehicle. Gastric tissue was analyzed for Nucb2 mRNA, protein content, and mTOR pathway activation. Gastric secretomes (collected from tissue explants) and plasma were assayed for nesfatin-1 levels.
Why This Research Matters
This study reveals a specific mechanism by which the cannabinoid system in the stomach, not the brain, regulates appetite. The mTOR pathway connection is important because mTOR is a central cellular energy sensor. This peripheral circuit could be targeted to reduce appetite without affecting the brain.
The Bigger Picture
The stomach is not just a digestive organ; it is an endocrine organ that sends satiety signals to the brain. This study shows the cannabinoid system regulates one of these signals (nesfatin-1) through a specific cellular pathway. Understanding this circuit could lead to appetite-controlling medications that work peripherally, avoiding the psychiatric side effects of brain-acting CB1 blockers.
What This Study Doesn't Tell Us
Animal study using injected drugs. Rimonabant was withdrawn from human use due to psychiatric side effects. The gastric mTOR-nesfatin pathway may differ between rats and humans. Only acute effects were measured.
Questions This Raises
- ?Would peripherally restricted CB1 blockers activate this same gastric nesfatin pathway?
- ?Does chronic cannabis use suppress gastric nesfatin-1, contributing to the appetite-stimulating effects of THC?
- ?Could nesfatin-1 itself be developed as an appetite suppressant?
Trust & Context
- Key Stat:
- Stomach CB1 blockade increased the satiety hormone nesfatin-1 through mTOR signaling
- Evidence Grade:
- Animal study with pharmacological confirmation using two CB1 antagonists and pathway inhibition. Strong mechanistic data but animal only.
- Study Age:
- Published in 2017. Peripheral cannabinoid control of appetite hormones continues to be investigated.
- Original Title:
- Pharmacological inhibition of cannabinoid receptor 1 stimulates gastric release of nesfatin-1 via the mTOR pathway.
- Published In:
- World journal of gastroenterology, 23(35), 6403-6411 (2017)
- Authors:
- Folgueira, Cintia, Barja-Fernandez, Silvia, Prado, Laura, Al-Massadi, Omar, Castelao, Cecilia, Pena-Leon, Veronica, Gonzalez-Saenz, Patricia, Baltar, Javier, Baamonde, Ivan, Leis, Rosaura, Dieguez, Carlos, Pagotto, Uberto, Casanueva, Felipe F, Tovar, Sulay A, Nogueiras, Ruben, Seoane, Luisa M
- Database ID:
- RTHC-01382
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
What is nesfatin-1?
Nesfatin-1 is a peptide hormone produced in the stomach (and brain) that promotes satiety and reduces food intake. This study showed that the cannabinoid system in the stomach controls its release through a specific signaling pathway.
Does this explain the "munchies"?
Partially. If CB1 blockade increases nesfatin-1 (promoting fullness), then CB1 activation by THC may decrease nesfatin-1, reducing satiety signals and increasing appetite. This could be one of several peripheral mechanisms contributing to cannabis-induced hunger.
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Cite This Study
https://rethinkthc.com/research/RTHC-01382APA
Folgueira, Cintia; Barja-Fernandez, Silvia; Prado, Laura; Al-Massadi, Omar; Castelao, Cecilia; Pena-Leon, Veronica; Gonzalez-Saenz, Patricia; Baltar, Javier; Baamonde, Ivan; Leis, Rosaura; Dieguez, Carlos; Pagotto, Uberto; Casanueva, Felipe F; Tovar, Sulay A; Nogueiras, Ruben; Seoane, Luisa M. (2017). Pharmacological inhibition of cannabinoid receptor 1 stimulates gastric release of nesfatin-1 via the mTOR pathway.. World journal of gastroenterology, 23(35), 6403-6411. https://doi.org/10.3748/wjg.v23.i35.6403
MLA
Folgueira, Cintia, et al. "Pharmacological inhibition of cannabinoid receptor 1 stimulates gastric release of nesfatin-1 via the mTOR pathway.." World journal of gastroenterology, 2017. https://doi.org/10.3748/wjg.v23.i35.6403
RethinkTHC
RethinkTHC Research Database. "Pharmacological inhibition of cannabinoid receptor 1 stimula..." RTHC-01382. Retrieved from https://rethinkthc.com/research/folgueira-2017-pharmacological-inhibition-of-cannabinoid
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.