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The Atypical Cannabinoid Abn-CBD Reduces Inflammation and Protects Liver, Pancreas, and Adipose Tissue in a Mouse Model of Prediabetes and Non-alcoholic Fatty Liver Disease
Background and Aims: The synthetic atypical cannabinoid Abn-CBD, a cannabidiol (CBD) derivative, has been recently shown to modulate the immune system in different organs, but its impact in obesity-related meta-inflammation remains unstudied. We investigated the effects of Abn-CBD on metabolic and i...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067697/ https://www.ncbi.nlm.nih.gov/pubmed/32210914 http://dx.doi.org/10.3389/fendo.2020.00103 |
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author | Romero-Zerbo, Silvana Y. García-Fernández, María Espinosa-Jiménez, Vanesa Pozo-Morales, Macarena Escamilla-Sánchez, Alejandro Sánchez-Salido, Lourdes Lara, Estrella Cobo-Vuilleumier, Nadia Rafacho, Alex Olveira, Gabriel Rojo-Martínez, Gemma Gauthier, Benoit R. González-Mariscal, Isabel Bermúdez-Silva, Francisco J. |
author_facet | Romero-Zerbo, Silvana Y. García-Fernández, María Espinosa-Jiménez, Vanesa Pozo-Morales, Macarena Escamilla-Sánchez, Alejandro Sánchez-Salido, Lourdes Lara, Estrella Cobo-Vuilleumier, Nadia Rafacho, Alex Olveira, Gabriel Rojo-Martínez, Gemma Gauthier, Benoit R. González-Mariscal, Isabel Bermúdez-Silva, Francisco J. |
author_sort | Romero-Zerbo, Silvana Y. |
collection | PubMed |
description | Background and Aims: The synthetic atypical cannabinoid Abn-CBD, a cannabidiol (CBD) derivative, has been recently shown to modulate the immune system in different organs, but its impact in obesity-related meta-inflammation remains unstudied. We investigated the effects of Abn-CBD on metabolic and inflammatory parameters utilizing a diet-induced obese (DIO) mouse model of prediabetes and non-alcoholic fatty liver disease (NAFLD). Materials and Methods: Ten-week-old C57Bl/6J mice were fed a high-fat diet for 15 weeks, following a 2-week treatment of daily intraperitoneal injections with Abn-CBD or vehicle. At week 15 mice were obese, prediabetic and developed NAFLD. Body weight and glucose homeostasis were monitored. Mice were euthanized and blood, liver, adipose tissue and pancreas were collected and processed for metabolic and inflammatory analysis. Results: Body weight and triglycerides profiles in blood and liver were comparable between vehicle- and Abn-CBD-treated DIO mice. However, treatment with Abn-CBD reduced hyperinsulinemia and markers of systemic low-grade inflammation in plasma and fat, also promoting white adipose tissue browning. Pancreatic islets from Abn-CBD-treated mice showed lower apoptosis, inflammation and oxidative stress than vehicle-treated DIO mice, and beta cell proliferation was induced. Furthermore, Abn-CBD lowered hepatic fibrosis, inflammation and macrophage infiltration in the liver when compared to vehicle-treated DIO mice. Importantly, the balance between hepatocyte proliferation and apoptosis was improved in Abn-CBD-treated compared to vehicle-treated DIO mice. Conclusions: These results suggest that Abn-CBD exerts beneficial immunomodulatory actions in the liver, pancreas and adipose tissue of DIO prediabetic mice with NAFLD, thus protecting tissues. Therefore, Abn-CBD and related compounds could represent novel pharmacological strategies for managing obesity-related metabolic disorders. |
format | Online Article Text |
id | pubmed-7067697 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-70676972020-03-24 The Atypical Cannabinoid Abn-CBD Reduces Inflammation and Protects Liver, Pancreas, and Adipose Tissue in a Mouse Model of Prediabetes and Non-alcoholic Fatty Liver Disease Romero-Zerbo, Silvana Y. García-Fernández, María Espinosa-Jiménez, Vanesa Pozo-Morales, Macarena Escamilla-Sánchez, Alejandro Sánchez-Salido, Lourdes Lara, Estrella Cobo-Vuilleumier, Nadia Rafacho, Alex Olveira, Gabriel Rojo-Martínez, Gemma Gauthier, Benoit R. González-Mariscal, Isabel Bermúdez-Silva, Francisco J. Front Endocrinol (Lausanne) Endocrinology Background and Aims: The synthetic atypical cannabinoid Abn-CBD, a cannabidiol (CBD) derivative, has been recently shown to modulate the immune system in different organs, but its impact in obesity-related meta-inflammation remains unstudied. We investigated the effects of Abn-CBD on metabolic and inflammatory parameters utilizing a diet-induced obese (DIO) mouse model of prediabetes and non-alcoholic fatty liver disease (NAFLD). Materials and Methods: Ten-week-old C57Bl/6J mice were fed a high-fat diet for 15 weeks, following a 2-week treatment of daily intraperitoneal injections with Abn-CBD or vehicle. At week 15 mice were obese, prediabetic and developed NAFLD. Body weight and glucose homeostasis were monitored. Mice were euthanized and blood, liver, adipose tissue and pancreas were collected and processed for metabolic and inflammatory analysis. Results: Body weight and triglycerides profiles in blood and liver were comparable between vehicle- and Abn-CBD-treated DIO mice. However, treatment with Abn-CBD reduced hyperinsulinemia and markers of systemic low-grade inflammation in plasma and fat, also promoting white adipose tissue browning. Pancreatic islets from Abn-CBD-treated mice showed lower apoptosis, inflammation and oxidative stress than vehicle-treated DIO mice, and beta cell proliferation was induced. Furthermore, Abn-CBD lowered hepatic fibrosis, inflammation and macrophage infiltration in the liver when compared to vehicle-treated DIO mice. Importantly, the balance between hepatocyte proliferation and apoptosis was improved in Abn-CBD-treated compared to vehicle-treated DIO mice. Conclusions: These results suggest that Abn-CBD exerts beneficial immunomodulatory actions in the liver, pancreas and adipose tissue of DIO prediabetic mice with NAFLD, thus protecting tissues. Therefore, Abn-CBD and related compounds could represent novel pharmacological strategies for managing obesity-related metabolic disorders. Frontiers Media S.A. 2020-03-06 /pmc/articles/PMC7067697/ /pubmed/32210914 http://dx.doi.org/10.3389/fendo.2020.00103 Text en Copyright © 2020 Romero-Zerbo, García-Fernández, Espinosa-Jiménez, Pozo-Morales, Escamilla-Sánchez, Sánchez-Salido, Lara, Cobo-Vuilleumier, Rafacho, Olveira, Rojo-Martínez, Gauthier, González-Mariscal and Bermúdez-Silva. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Endocrinology Romero-Zerbo, Silvana Y. García-Fernández, María Espinosa-Jiménez, Vanesa Pozo-Morales, Macarena Escamilla-Sánchez, Alejandro Sánchez-Salido, Lourdes Lara, Estrella Cobo-Vuilleumier, Nadia Rafacho, Alex Olveira, Gabriel Rojo-Martínez, Gemma Gauthier, Benoit R. González-Mariscal, Isabel Bermúdez-Silva, Francisco J. The Atypical Cannabinoid Abn-CBD Reduces Inflammation and Protects Liver, Pancreas, and Adipose Tissue in a Mouse Model of Prediabetes and Non-alcoholic Fatty Liver Disease |
title | The Atypical Cannabinoid Abn-CBD Reduces Inflammation and Protects Liver, Pancreas, and Adipose Tissue in a Mouse Model of Prediabetes and Non-alcoholic Fatty Liver Disease |
title_full | The Atypical Cannabinoid Abn-CBD Reduces Inflammation and Protects Liver, Pancreas, and Adipose Tissue in a Mouse Model of Prediabetes and Non-alcoholic Fatty Liver Disease |
title_fullStr | The Atypical Cannabinoid Abn-CBD Reduces Inflammation and Protects Liver, Pancreas, and Adipose Tissue in a Mouse Model of Prediabetes and Non-alcoholic Fatty Liver Disease |
title_full_unstemmed | The Atypical Cannabinoid Abn-CBD Reduces Inflammation and Protects Liver, Pancreas, and Adipose Tissue in a Mouse Model of Prediabetes and Non-alcoholic Fatty Liver Disease |
title_short | The Atypical Cannabinoid Abn-CBD Reduces Inflammation and Protects Liver, Pancreas, and Adipose Tissue in a Mouse Model of Prediabetes and Non-alcoholic Fatty Liver Disease |
title_sort | atypical cannabinoid abn-cbd reduces inflammation and protects liver, pancreas, and adipose tissue in a mouse model of prediabetes and non-alcoholic fatty liver disease |
topic | Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067697/ https://www.ncbi.nlm.nih.gov/pubmed/32210914 http://dx.doi.org/10.3389/fendo.2020.00103 |
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