Abstract
Endocannabinoid Signaling In Spinal Sensory Neurons of the Gut Regulates Food Intake
Obesity (Silver Spring, Md.), Vol.31(S2), pp.35-35
11/01/2023
Abstract
Background: We previously showed that administration of an Endocannabinoid receptor-1 (CB1) inverse agonist (Rimonabant) induced an increase in splanchnic nerve activity, and "browning" of mesenteric fat. Furthermore, we demonstrated that selective splanchnic denervation significantly reduces the response to Rimonabant, specifically on food intake. Hypothesis: we examined if the sensory/spinal branch of the splanchnic nerve mediates the effect on energy balance and food intake. Methods: (1) We explored the localization of peripheral CB1 within the sensory nerve endings of the luminal gut and the effects of CB1-inverse agonist in mouse models of spinal afferent denervation on two obesogenic diets. (2) we also explored whether gastric bypassinduced changes in gut microbiome mediate its energy regulating effects through CB1 -signaling via the spinal/sensory pathway. Results: We found that intestinal CB1 co-localizes mainly with CGRPexpressing cells (sensory neurons) and not epithelial, enteroendocrine, or any immune cell. We found more significant co-localization of CB1 to the sensory/spinal fibers (celiac ganglion and DRG) than vagal sensory fibers (nodose ganglion). Then, using a model of selective afferent splanchnic denervation we found that the effects of Rimonabant were attenuated only in denervated high-fat diet and not high-carb diet induced obese mice. Finally, transferring fecal material from RYGB and Sham -operated mice into naïf recipients induces a significant increase in afferent and efferent splanchnic nerve activity of RYGB-stool recipients compared to their controls. Finally, intestinal CB1 expression was significantly lower in RYGB-stool recipients compared to their controls. Conclusions: Gut microbiome communicate energy signals from the gut to the brain through sensory/spinal afferent neurons via a CB1-depenedent pathway.
Details
- Title: Subtitle
- Endocannabinoid Signaling In Spinal Sensory Neurons of the Gut Regulates Food Intake
- Creators
- Mohamad MokademBenjamin LindenMohammad JarrahHussein HerzYi Chu
- Resource Type
- Abstract
- Publication Details
- Obesity (Silver Spring, Md.), Vol.31(S2), pp.35-35
- Publisher
- Blackwell Publishing Ltd
- ISSN
- 1930-7381
- eISSN
- 1930-739X
- Comment
- (2023), Oral Abstracts. Obesity (Silver Spring), 31: 5-52. https://doi.org/10.1002/oby.23938
- Language
- English
- Date published
- 11/01/2023
- Academic Unit
- Surgery; Gastroenterology and Hepatology; Internal Medicine
- Record Identifier
- 9984628049902771
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