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...
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Frontiers Media S.A.
2020-03-01
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Online Access: | https://www.frontiersin.org/article/10.3389/fendo.2020.00103/full |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Silvana Y. Romero-Zerbo María García-Fernández Vanesa Espinosa-Jiménez Macarena Pozo-Morales Alejandro Escamilla-Sánchez Lourdes Sánchez-Salido Estrella Lara Nadia Cobo-Vuilleumier Alex Rafacho Gabriel Olveira Gabriel Olveira Gemma Rojo-Martínez Gemma Rojo-Martínez Benoit R. Gauthier Benoit R. Gauthier Isabel González-Mariscal Francisco J. Bermúdez-Silva Francisco J. Bermúdez-Silva |
spellingShingle |
Silvana Y. Romero-Zerbo María García-Fernández Vanesa Espinosa-Jiménez Macarena Pozo-Morales Alejandro Escamilla-Sánchez Lourdes Sánchez-Salido Estrella Lara Nadia Cobo-Vuilleumier Alex Rafacho Gabriel Olveira Gabriel Olveira Gemma Rojo-Martínez Gemma Rojo-Martínez Benoit R. Gauthier Benoit R. Gauthier Isabel González-Mariscal Francisco J. Bermúdez-Silva Francisco J. Bermúdez-Silva 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 Frontiers in Endocrinology cannabinoids inflammation prediabetes NAFLD obesity liver |
author_facet |
Silvana Y. Romero-Zerbo María García-Fernández Vanesa Espinosa-Jiménez Macarena Pozo-Morales Alejandro Escamilla-Sánchez Lourdes Sánchez-Salido Estrella Lara Nadia Cobo-Vuilleumier Alex Rafacho Gabriel Olveira Gabriel Olveira Gemma Rojo-Martínez Gemma Rojo-Martínez Benoit R. Gauthier Benoit R. Gauthier Isabel González-Mariscal Francisco J. Bermúdez-Silva Francisco J. Bermúdez-Silva |
author_sort |
Silvana Y. Romero-Zerbo |
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_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_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_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 |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Endocrinology |
issn |
1664-2392 |
publishDate |
2020-03-01 |
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. |
topic |
cannabinoids inflammation prediabetes NAFLD obesity liver |
url |
https://www.frontiersin.org/article/10.3389/fendo.2020.00103/full |
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doaj-2e3857d829864ea1b67a62e47e1c64612020-11-25T03:07:38ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922020-03-011110.3389/fendo.2020.00103513555The Atypical Cannabinoid Abn-CBD Reduces Inflammation and Protects Liver, Pancreas, and Adipose Tissue in a Mouse Model of Prediabetes and Non-alcoholic Fatty Liver DiseaseSilvana Y. Romero-Zerbo0María García-Fernández1Vanesa Espinosa-Jiménez2Macarena Pozo-Morales3Alejandro Escamilla-Sánchez4Lourdes Sánchez-Salido5Estrella Lara6Nadia Cobo-Vuilleumier7Alex Rafacho8Gabriel Olveira9Gabriel Olveira10Gemma Rojo-Martínez11Gemma Rojo-Martínez12Benoit R. Gauthier13Benoit R. Gauthier14Isabel González-Mariscal15Francisco J. Bermúdez-Silva16Francisco J. Bermúdez-Silva17UGC Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Regional de Málaga, Universidad de Málaga, Málaga, SpainDepartamento de Fisiología Humana, Facultad de Medicina, Instituto de Investigación Biomédica de Málaga-IBIMA, Universidad de Málaga, Málaga, SpainUGC Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Regional de Málaga, Universidad de Málaga, Málaga, SpainUGC Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Regional de Málaga, Universidad de Málaga, Málaga, SpainPlataforma de Microscopía, Instituto de Investigación Biomédica de Málaga-IBIMA, Málaga, SpainUGC Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Regional de Málaga, Universidad de Málaga, Málaga, SpainDepartamento de Fisiología Humana, Facultad de Medicina, Instituto de Investigación Biomédica de Málaga-IBIMA, Universidad de Málaga, Málaga, SpainAndalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), Seville, SpainLaboratory of Investigation in Chronic Diseases - LIDoC, Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina (UFSC), Florianópolis, BrazilUGC Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Regional de Málaga, Universidad de Málaga, Málaga, SpainCentro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, SpainUGC Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Regional de Málaga, Universidad de Málaga, Málaga, SpainCentro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, SpainAndalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), Seville, SpainCentro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, SpainUGC Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Regional de Málaga, Universidad de Málaga, Málaga, SpainUGC Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Regional de Málaga, Universidad de Málaga, Málaga, SpainCentro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, SpainBackground 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.https://www.frontiersin.org/article/10.3389/fendo.2020.00103/fullcannabinoidsinflammationprediabetesNAFLDobesityliver |