1. 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
- Author
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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, Gemma Rojo-Martínez, Benoit R. Gauthier, Isabel González-Mariscal, Francisco J. Bermúdez-Silva, [Romero-Zerbo,SY, Espinosa-Jiménez,V, Pozo-Morales,M, Sánchez-Salido,L, Olveira,G, Rojo-Martínez,G, González-Mariscal,I, Bermúdez-Silva, FJ] UGC Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Regional de Málaga, Universidad de Málaga, Málaga, Spain. [García-Fernández,M, Lara,E, ] Departamento de Fisiología Humana, Facultad de Medicina, Instituto de Investigación Biomédica de Málaga-IBIMA, Universidad de Málaga, Málaga, Spain. [Escamilla-Sánchez,A] Plataforma de Microscopía, Instituto de Investigación Biomédica de Málaga-IBIMA, Málaga, Spain. [Cobo-Vuilleumier,N, Gauthier,BR] Andalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), Seville, Spain. [Rafacho,A] Laboratory of Investigation in Chronic Diseases - LIDoC, Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina (UFSC), Florianópolis, Brazil. [Olveira,G, Gauthier,BR, Bermúdez-Silva,FJ] Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain., This work was supported by Consejería de Salud de la Junta de Andalucía Andalucía se mueve con Europa (PI-0574-2012 to SR-Z) and Instituto de Salud Carlos III (ISCIII), Ministerio de Sanidad, Gobierno de España Una manera de hacer Europa (13/00309 and 17/01004 to FB-S, co-funded by FEDER, EU). SR-Z was recipient of a postdoctoral fellowship from Consejeria de Salud de la Junta de Andalucia (RH-0070-2013). AR received a short-term stay fellowship from Banco Santander (Programa Bolsas Iberoamericanas Jovens Professores e Pesquisadores) and was funded by a CNPq research grant (Grant No. 306359/2017-0). IG-M was funded by the European Commission Research & Innovation, Horizon2020 program, call H2020-MSCA-IF-2016 (GA: 748749). FB-S belongs to the regional Nicolás Monardes research program of the Consejería de Salud (C-0070-2012 and RC0005-2016, Junta de Andalucía, Spain). BG was supported by the Ministerio de Economia y Competitividad co-funded by FEDER (PI10/00871, PI13/00593 and BFU2017-83588-P). CIBERDEM is an initiative of the Instituto de Salud Carlos III., Junta de Andalucía, European Commission, Instituto de Salud Carlos III, Ministerio de Sanidad (España), Banco Santander, Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brasil), Ministerio de Economía y Competitividad (España), Agencia Estatal de Investigación (España), and Ministerio de Ciencia, Innovación y Universidades (España)
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Male ,0301 basic medicine ,obesity ,Anatomy::Digestive System::Liver [Medical Subject Headings] ,Endocrinology, Diabetes and Metabolism ,Obesidad ,Mice, Obese ,Adipose tissue ,White adipose tissue ,prediabetes ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,Mice ,Endocrinology ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,Organisms::Eukaryota::Animals [Medical Subject Headings] ,Hyperinsulinemia ,Medicine ,Glucose homeostasis ,Original Research ,Anatomy::Digestive System::Pancreas [Medical Subject Headings] ,Hígado ,Fatty liver ,Islets of langerhans ,Enfermedad del hígado graso no alcohólico ,Anatomy::Tissues::Connective Tissue::Adipose Tissue [Medical Subject Headings] ,3. Good health ,medicine.anatomical_structure ,surgical procedures, operative ,Adipose Tissue ,Liver ,Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Benzene Derivatives::Phenols::Resorcinols [Medical Subject Headings] ,Cannabinoides ,Phenomena and Processes::Physiological Phenomena::Pharmacological Phenomena::Pharmacological Processes::Cytoprotection [Medical Subject Headings] ,islets of Langerhans ,medicine.symptom ,Beta cell ,Tejido adiposo ,medicine.medical_specialty ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice, Mutant Strains::Mice, Obese [Medical Subject Headings] ,Check Tags::Male [Medical Subject Headings] ,Diseases::Digestive System Diseases::Liver Diseases::Fatty Liver [Medical Subject Headings] ,030209 endocrinology & metabolism ,Inflammation ,Diet, High-Fat ,liver ,digestive system ,Prediabetic State ,03 medical and health sciences ,cannabinoids ,Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet::Diet, High-Fat [Medical Subject Headings] ,Internal medicine ,NAFLD ,Animals ,Obesity ,Pancreas ,Diseases::Endocrine System Diseases::Diabetes Mellitus::Prediabetic State [Medical Subject Headings] ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice [Medical Subject Headings] ,lcsh:RC648-665 ,Inflamación ,Cannabinoids ,business.industry ,Pancreatic islets ,Resorcinols ,medicine.disease ,digestive system diseases ,Islotes pancreáticos ,Diseases::Animal Diseases::Disease Models, Animal [Medical Subject Headings] ,Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity [Medical Subject Headings] ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,Cytoprotection ,inflammation ,Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Laboratory::Animals, Inbred Strains::Mice, Inbred Strains::Mice, Inbred C57BL [Medical Subject Headings] ,business ,Prediabetes ,Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Inflammation [Medical Subject Headings] - 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., This work was supported by Consejería de Salud de la Junta de Andalucía Andalucía se mueve con Europa (PI-0574-2012 to SR-Z) and Instituto de Salud Carlos III (ISCIII), Ministerio de Sanidad, Gobierno de España Una manera de hacer Europa (13/00309 and 17/01004 to FB-S, co-funded by FEDER, EU). SR-Z was recipient of a postdoctoral fellowship from Consejeria de Salud de la Junta de Andalucia (RH-0070-2013). AR received a short-term stay fellowship from Banco Santander (Programa Bolsas Iberoamericanas Jovens Professores e Pesquisadores) and was funded by a CNPq research grant (Grant No. 306359/2017-0). IG-M was funded by the European Commission Research & Innovation, Horizon2020 program, call H2020-MSCA-IF-2016 (GA: 748749). FB-S belongs to the regional Nicolás Monardes research program of the Consejería de Salud (C-0070-2012 and RC0005-2016; Junta de Andalucía, Spain). BG was supported by the Ministerio de Economia y Competitividad co-funded by FEDER (PI10/00871, PI13/00593 and BFU2017-83588-P). CIBERDEM is an initiative of the Instituto de Salud Carlos III.
- Published
- 2020
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