An Alternative Pharmacological Therapy for Obesity Through Modulation of Vagus Nerve Synaptic Receptors
- 1Centro Diabete, Ospedale Sandro Pertini, 00157 Rome, Italy
Abstract
Obesity is a rapidly spreading disease globally. It causes serious complications, including type 2 diabetes, hypertension, dyslipidemia, fatty liver disease, and other serious cardiovascular consequences. Weight loss, the primary driver of the healing process, is extremely difficult to achieve due to the body’s strong resistance, a legacy of an evolutionary process that protected the human species from extinction due to nutritional deficiency. The few drugs currently available and recognized as effective, however, are not free from side effects and, more importantly, do not guarantee a permanent cure, but only a temporary suspension of symptoms during administration. Bariatric surgery, however, has proven highly effective. The ideal goal would be to find an equally effective pharmacological solution that reproduces the same mechanism. Currently, only hypotheses exist. Many clues point to a modified function of the ascending vagal afferent fibers that connect the gastro-intestinal tract to the brain. In this narrative, hypothesis-driven review, it is hypothesized that pharmacological modulation of glutamatergic (NMDA) receptors at the synapses between vagal afferent fibers and their central targets may represent a novel therapeutic strategy for obesity. This approach would target the putative altered mechanism present in obesity, with the hypothetical potential to promote sustained weight loss or durable disease modification, pending experimental and clinical confirmation. There are already some encouraging signs in this direction.
Related
- Pharmacological targeting of bunyavirus-induced synaptic impairment prevents neuronal hyperexcitability
- Pharmacological Analysis of P2Y Purinergic Receptors That Modulate the Rat Vasopressor Sympathetic Tone.
- Positive Allosteric Modulation of mGlu and Muscarinic Receptors Differentially Regulate Nitric Oxide-Dependent Signaling in a Scopolamine-Induced Model of Cognitive Impairment
- Selective excitatory effects of γ‐glutamyl‐glycine, a glutathione metabolite, on GluN1 NMDA and mGlu5 receptors impacting synaptic plasticity
- Editorial: Pharmacological modulation of inflammatory pathways in sepsis: targeting the cytokine storm and septic oxidative stress
BibTeX
@article{blasi2026alternative,
title = {{An Alternative Pharmacological Therapy for Obesity Through Modulation of Vagus Nerve Synaptic Receptors}},
author = {Claudio Blasi},
journal = {Journal of Clinical Medicine},
year = {2026},
month = oct,
doi = {10.3390/jcm15207914},
url = {https://www.mdpi.com/2077-0383/15/20/7914},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - An Alternative Pharmacological Therapy for Obesity Through Modulation of Vagus Nerve Synaptic Receptors
AU - Claudio Blasi
PY - 2026
DA - 2026/10/14
JO - Journal of Clinical Medicine
DO - 10.3390/jcm15207914
UR - https://www.mdpi.com/2077-0383/15/20/7914
AB - Obesity is a rapidly spreading disease globally. It causes serious complications, including type 2 diabetes, hypertension, dyslipidemia, fatty liver disease, and other serious cardiovascular consequences. Weight loss, the primary driver of the healing process, is extremely difficult to achieve due to the body’s strong resistance, a legacy of an evolutionary process that protected the human species from extinction due to nutritional deficiency. The few drugs currently available and recognized as effective, however, are not free from side effects and, more importantly, do not guarantee a permanent cure, but only a temporary suspension of symptoms during administration. Bariatric surgery, however, has proven highly effective. The ideal goal would be to find an equally effective pharmacological solution that reproduces the same mechanism. Currently, only hypotheses exist. Many clues point to a modified function of the ascending vagal afferent fibers that connect the gastro-intestinal tract to the brain. In this narrative, hypothesis-driven review, it is hypothesized that pharmacological modulation of glutamatergic (NMDA) receptors at the synapses between vagal afferent fibers and their central targets may represent a novel therapeutic strategy for obesity. This approach would target the putative altered mechanism present in obesity, with the hypothetical potential to promote sustained weight loss or durable disease modification, pending experimental and clinical confirmation. There are already some encouraging signs in this direction.
SN - 2077-0383
ER -