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Cannabinoid Receptor Stimulation Impairs Mitochondrial Biogenesis in Mouse White Adipose Tissue, Muscle, and Liver: The Role of eNOS, p38 MAPK, and AMPK Pathways
OBJECTIVE: Cannabinoid type 1 (CB1) receptor is involved in whole-body and cellular energy metabolism. We asked whether CB1 receptor stimulation was able to decrease mitochondrial biogenesis in different metabolically active tissues of obese high-fat diet (HFD)-fed mice. RESEARCH DESIGN AND METHODS:...
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2963541/ https://www.ncbi.nlm.nih.gov/pubmed/20739683 http://dx.doi.org/10.2337/db09-1881 |
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author | Tedesco, Laura Valerio, Alessandra Dossena, Marta Cardile, Annalisa Ragni, Maurizio Pagano, Claudio Pagotto, Uberto Carruba, Michele O. Vettor, Roberto Nisoli, Enzo |
author_facet | Tedesco, Laura Valerio, Alessandra Dossena, Marta Cardile, Annalisa Ragni, Maurizio Pagano, Claudio Pagotto, Uberto Carruba, Michele O. Vettor, Roberto Nisoli, Enzo |
author_sort | Tedesco, Laura |
collection | PubMed |
description | OBJECTIVE: Cannabinoid type 1 (CB1) receptor is involved in whole-body and cellular energy metabolism. We asked whether CB1 receptor stimulation was able to decrease mitochondrial biogenesis in different metabolically active tissues of obese high-fat diet (HFD)-fed mice. RESEARCH DESIGN AND METHODS: The effects of selective CB1 agonist arachidonyl-2-chloroethanolamide (ACEA) and endocannabinoids anandamide and 2-arachidonoylglycerol on endothelial nitric oxide synthase (eNOS) expression were examined, as were mitochondrial DNA amount and mitochondrial biogenesis parameters in cultured mouse and human white adipocytes. These parameters were also investigated in white adipose tissue (WAT), muscle, and liver of mice chronically treated with ACEA. Moreover, p38 mitogen-activated protein kinase (MAPK) phosphorylation was investigated in WAT and isolated mature adipocytes from eNOS(−/−) and wild-type mice. eNOS, p38 MAPK, adenosine monophosphate–activated protein kinase (AMPK), and mitochondrial biogenesis were investigated in WAT, muscle, and liver of HFD mice chronically treated with ACEA. RESULTS: ACEA decreased mitochondrial biogenesis and eNOS expression, activated p38 MAPK, and reduced AMPK phosphorylation in white adipocytes. The ACEA effects on mitochondria were antagonized by nitric oxide donors and by p38 MAPK silencing. White adipocytes from eNOS(−/−) mice displayed higher p38 MAPK phosphorylation than wild-type animals under basal conditions, and ACEA was ineffective in cells lacking eNOS. Moreover, mitochondrial biogenesis was downregulated, while p38 MAPK phosphorylation was increased and AMPK phosphorylation was decreased in WAT, muscle, and liver of ACEA-treated mice on a HFD. CONCLUSIONS: CB1 receptor stimulation decreases mitochondrial biogenesis in white adipocytes, through eNOS downregulation and p38 MAPK activation, and impairs mitochondrial function in metabolically active tissues of dietary obese mice. |
format | Text |
id | pubmed-2963541 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-29635412011-11-01 Cannabinoid Receptor Stimulation Impairs Mitochondrial Biogenesis in Mouse White Adipose Tissue, Muscle, and Liver: The Role of eNOS, p38 MAPK, and AMPK Pathways Tedesco, Laura Valerio, Alessandra Dossena, Marta Cardile, Annalisa Ragni, Maurizio Pagano, Claudio Pagotto, Uberto Carruba, Michele O. Vettor, Roberto Nisoli, Enzo Diabetes Obesity Studies OBJECTIVE: Cannabinoid type 1 (CB1) receptor is involved in whole-body and cellular energy metabolism. We asked whether CB1 receptor stimulation was able to decrease mitochondrial biogenesis in different metabolically active tissues of obese high-fat diet (HFD)-fed mice. RESEARCH DESIGN AND METHODS: The effects of selective CB1 agonist arachidonyl-2-chloroethanolamide (ACEA) and endocannabinoids anandamide and 2-arachidonoylglycerol on endothelial nitric oxide synthase (eNOS) expression were examined, as were mitochondrial DNA amount and mitochondrial biogenesis parameters in cultured mouse and human white adipocytes. These parameters were also investigated in white adipose tissue (WAT), muscle, and liver of mice chronically treated with ACEA. Moreover, p38 mitogen-activated protein kinase (MAPK) phosphorylation was investigated in WAT and isolated mature adipocytes from eNOS(−/−) and wild-type mice. eNOS, p38 MAPK, adenosine monophosphate–activated protein kinase (AMPK), and mitochondrial biogenesis were investigated in WAT, muscle, and liver of HFD mice chronically treated with ACEA. RESULTS: ACEA decreased mitochondrial biogenesis and eNOS expression, activated p38 MAPK, and reduced AMPK phosphorylation in white adipocytes. The ACEA effects on mitochondria were antagonized by nitric oxide donors and by p38 MAPK silencing. White adipocytes from eNOS(−/−) mice displayed higher p38 MAPK phosphorylation than wild-type animals under basal conditions, and ACEA was ineffective in cells lacking eNOS. Moreover, mitochondrial biogenesis was downregulated, while p38 MAPK phosphorylation was increased and AMPK phosphorylation was decreased in WAT, muscle, and liver of ACEA-treated mice on a HFD. CONCLUSIONS: CB1 receptor stimulation decreases mitochondrial biogenesis in white adipocytes, through eNOS downregulation and p38 MAPK activation, and impairs mitochondrial function in metabolically active tissues of dietary obese mice. American Diabetes Association 2010-11 2010-08-25 /pmc/articles/PMC2963541/ /pubmed/20739683 http://dx.doi.org/10.2337/db09-1881 Text en © 2010 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Obesity Studies Tedesco, Laura Valerio, Alessandra Dossena, Marta Cardile, Annalisa Ragni, Maurizio Pagano, Claudio Pagotto, Uberto Carruba, Michele O. Vettor, Roberto Nisoli, Enzo Cannabinoid Receptor Stimulation Impairs Mitochondrial Biogenesis in Mouse White Adipose Tissue, Muscle, and Liver: The Role of eNOS, p38 MAPK, and AMPK Pathways |
title | Cannabinoid Receptor Stimulation Impairs Mitochondrial Biogenesis in Mouse White Adipose Tissue, Muscle, and Liver: The Role of eNOS, p38 MAPK, and AMPK Pathways |
title_full | Cannabinoid Receptor Stimulation Impairs Mitochondrial Biogenesis in Mouse White Adipose Tissue, Muscle, and Liver: The Role of eNOS, p38 MAPK, and AMPK Pathways |
title_fullStr | Cannabinoid Receptor Stimulation Impairs Mitochondrial Biogenesis in Mouse White Adipose Tissue, Muscle, and Liver: The Role of eNOS, p38 MAPK, and AMPK Pathways |
title_full_unstemmed | Cannabinoid Receptor Stimulation Impairs Mitochondrial Biogenesis in Mouse White Adipose Tissue, Muscle, and Liver: The Role of eNOS, p38 MAPK, and AMPK Pathways |
title_short | Cannabinoid Receptor Stimulation Impairs Mitochondrial Biogenesis in Mouse White Adipose Tissue, Muscle, and Liver: The Role of eNOS, p38 MAPK, and AMPK Pathways |
title_sort | cannabinoid receptor stimulation impairs mitochondrial biogenesis in mouse white adipose tissue, muscle, and liver: the role of enos, p38 mapk, and ampk pathways |
topic | Obesity Studies |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2963541/ https://www.ncbi.nlm.nih.gov/pubmed/20739683 http://dx.doi.org/10.2337/db09-1881 |
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