Publication:
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

Loading...
Thumbnail Image

Date

2020-03-06

Authors

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

Advisors

Journal Title

Journal ISSN

Volume Title

Publisher

Frontiers
Metrics
Google Scholar
Export

Research Projects

Organizational Units

Journal Issue

Abstract

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.

Description

MeSH Terms

Medical Subject Headings::Anatomy::Tissues::Connective Tissue::Adipose Tissue
Medical Subject Headings::Organisms::Eukaryota::Animals
Medical Subject Headings::Phenomena and Processes::Physiological Phenomena::Pharmacological Phenomena::Pharmacological Processes::Cytoprotection
Medical Subject Headings::Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet::Diet, High-Fat
Medical Subject Headings::Diseases::Animal Diseases::Disease Models, Animal
Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Inflammation
Medical Subject Headings::Anatomy::Digestive System::Liver
Medical Subject Headings::Check Tags::Male
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice
Medical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Laboratory::Animals, Inbred Strains::Mice, Inbred Strains::Mice, Inbred C57BL
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice, Mutant Strains::Mice, Obese
Medical Subject Headings::Diseases::Digestive System Diseases::Liver Diseases::Fatty Liver
Medical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity
Medical Subject Headings::Anatomy::Digestive System::Pancreas
Medical Subject Headings::Diseases::Endocrine System Diseases::Diabetes Mellitus::Prediabetic State
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Benzene Derivatives::Phenols::Resorcinols

DeCS Terms

CIE Terms

Keywords

Cannabinoids, Inflammation, Prediabetes, NAFLD, Obesity, Liver, Islets of langerhans, Adipose tissue, Cannabinoides, Inflamación, Enfermedad del hígado graso no alcohólico, Obesidad, Hígado, Islotes pancreáticos, Tejido adiposo

Citation

Romero-Zerbo SY, García-Fernández M, Espinosa-Jiménez V, Pozo-Morales M, Escamilla-Sánchez A, Sánchez-Salido L, et al. 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. Front Endocrinol. 2020 Mar 6;11:103