Cannabidiol - A phytocannabinoid that widely affects sphingolipid metabolism under conditions of brain insulin resistance.

Abstract

Obesity-related insulin resistance (IR) and attenuated brain insulin signaling are significant risk factors for neurodegenerative disorders, e.g., Alzheimer's disease. IR and type 2 diabetes correlate with an increased concentration of sphingolipids, a class of lipids that play an essential structural role in cellular membranes and cell signaling pathways. Cannabidiol (CBD) is a nonpsychoactive constituent of Cannabis sativa plant that interacts with the endocannabinoidome. Despite known positive effects of CBD on improvement in diabetes and its aftermath, e.g., anti-inflammatory and anti-oxidant effects, there are no studies evaluating the effect of phytocannabinoids on the brain insulin resistance and sphingolipid metabolism. Our experiment was carried out on Wistar rats that received a high-fat diet and/or intraperitoneal CBD injections. In our study, we indicated inhibition of de novo synthesis and salvage pathways, which resulted in significant changes in the concentration of sphingolipids, e.g., ceramide and sphingomyelin. Furthermore, we observed reduced brain IR and decreased tau protein phosphorylation what might be protective against neuropathologies development. We believe that our research will concern a new possible therapeutic approach with Cannabis -plant derived compounds and within a few years, cannabinoids would be considered as prominent substances for targeting both metabolic and neurodegenerative pathologies.

• Authors: Tomasz Charytoniuk, Klaudia Sztolsztener, Ewa Harasim-Symbor, Klaudia Berk, Adrian Chabowski, Karolina Konstantynowicz-Nowicka
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 142 Pg. 112057 (Oct 2021) ISSN: 1950-6007 [Electronic] France
• PMID: 34435590 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Ceramides
• Insulin
• Neuroprotective Agents
• Receptors, Cannabinoid
• Sphingolipids
• Sphingomyelins
• tau Proteins
• Cannabidiol

Topics

• Animals
• Brain (metabolism)
• Cannabidiol (administration & dosage, pharmacology)
• Ceramides (biosynthesis)
• Cerebral Cortex (drug effects, metabolism)
• Diabetes Mellitus, Experimental (chemically induced, complications)
• Diet, High-Fat (adverse effects)
• Insulin (metabolism)
• Insulin Resistance
• Lipid Metabolism (drug effects)
• Male
• Neurodegenerative Diseases (complications, drug therapy)
• Neuroprotective Agents (administration & dosage, pharmacology)
• Obesity (chemically induced, complications)
• Phosphorylation (drug effects)
• Rats, Wistar
• Receptors, Cannabinoid (metabolism)
• Signal Transduction (drug effects)
• Sphingolipids (metabolism)
• Sphingomyelins (metabolism)
• tau Proteins (metabolism)
• Rats