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Protein Kinase A Regulatory Subunits in Human Adipose Tissue: Decreased R2B Expression and Activity in Adipocytes From Obese Subjects
OBJECTIVE—In human adipocytes, the cAMP-dependent pathway mediates signals originating from β-adrenergic activation, thus playing a key role in the regulation of important metabolic processes, i.e., lipolysis and thermogenesis. Cyclic AMP effects are mainly mediated by protein kinase A (PKA), whose...
Autores principales: | , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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American Diabetes Association
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2646060/ https://www.ncbi.nlm.nih.gov/pubmed/19095761 http://dx.doi.org/10.2337/db08-0585 |
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author | Mantovani, Giovanna Bondioni, Sara Alberti, Luisella Gilardini, Luisa Invitti, Cecilia Corbetta, Sabrina Zappa, Marco A. Ferrero, Stefano Lania, Andrea G. Bosari, Silvano Beck-Peccoz, Paolo Spada, Anna |
author_facet | Mantovani, Giovanna Bondioni, Sara Alberti, Luisella Gilardini, Luisa Invitti, Cecilia Corbetta, Sabrina Zappa, Marco A. Ferrero, Stefano Lania, Andrea G. Bosari, Silvano Beck-Peccoz, Paolo Spada, Anna |
author_sort | Mantovani, Giovanna |
collection | PubMed |
description | OBJECTIVE—In human adipocytes, the cAMP-dependent pathway mediates signals originating from β-adrenergic activation, thus playing a key role in the regulation of important metabolic processes, i.e., lipolysis and thermogenesis. Cyclic AMP effects are mainly mediated by protein kinase A (PKA), whose R2B regulatory isoform is the most expressed in mouse adipose tissue, where it protects against diet-induced obesity and fatty liver development. The aim of the study was to investigate possible differences in R2B expression, PKA activity, and lipolysis in adipose tissues from obese and nonobese subjects. RESEARCH DESIGN AND METHODS—The expression of the different PKA regulatory subunits was evaluated by immunohistochemistry, Western blot, and real-time PCR in subcutaneous and visceral adipose tissue samples from 20 nonobese and 67 obese patients. PKA activity and glycerol release were evaluated in total protein extract and adipocytes isolated from fresh tissue samples, respectively. RESULTS—Expression techniques showed that R2B was the most abundant regulatory protein, both at mRNA and protein level. Interestingly, R2B mRNA levels were significantly lower in both subcutaneous and visceral adipose tissues from obese than nonobese patients and negatively correlated with BMI, waist circumference, insulin levels, and homeostasis model assessment of insulin resistance. Moreover, both basal and stimulated PKA activity and glycerol release were significantly lower in visceral adipose tissue from obese patients then nonobese subjects. CONCLUSIONS—Our results first indicate that, in human adipose tissue, there are important BMI-related differences in R2B expression and PKA activation, which might be included among the multiple determinants involved in the different lipolytic response to β-adrenergic activation in obesity. |
format | Text |
id | pubmed-2646060 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-26460602010-03-01 Protein Kinase A Regulatory Subunits in Human Adipose Tissue: Decreased R2B Expression and Activity in Adipocytes From Obese Subjects Mantovani, Giovanna Bondioni, Sara Alberti, Luisella Gilardini, Luisa Invitti, Cecilia Corbetta, Sabrina Zappa, Marco A. Ferrero, Stefano Lania, Andrea G. Bosari, Silvano Beck-Peccoz, Paolo Spada, Anna Diabetes Signal Transduction OBJECTIVE—In human adipocytes, the cAMP-dependent pathway mediates signals originating from β-adrenergic activation, thus playing a key role in the regulation of important metabolic processes, i.e., lipolysis and thermogenesis. Cyclic AMP effects are mainly mediated by protein kinase A (PKA), whose R2B regulatory isoform is the most expressed in mouse adipose tissue, where it protects against diet-induced obesity and fatty liver development. The aim of the study was to investigate possible differences in R2B expression, PKA activity, and lipolysis in adipose tissues from obese and nonobese subjects. RESEARCH DESIGN AND METHODS—The expression of the different PKA regulatory subunits was evaluated by immunohistochemistry, Western blot, and real-time PCR in subcutaneous and visceral adipose tissue samples from 20 nonobese and 67 obese patients. PKA activity and glycerol release were evaluated in total protein extract and adipocytes isolated from fresh tissue samples, respectively. RESULTS—Expression techniques showed that R2B was the most abundant regulatory protein, both at mRNA and protein level. Interestingly, R2B mRNA levels were significantly lower in both subcutaneous and visceral adipose tissues from obese than nonobese patients and negatively correlated with BMI, waist circumference, insulin levels, and homeostasis model assessment of insulin resistance. Moreover, both basal and stimulated PKA activity and glycerol release were significantly lower in visceral adipose tissue from obese patients then nonobese subjects. CONCLUSIONS—Our results first indicate that, in human adipose tissue, there are important BMI-related differences in R2B expression and PKA activation, which might be included among the multiple determinants involved in the different lipolytic response to β-adrenergic activation in obesity. American Diabetes Association 2009-03 /pmc/articles/PMC2646060/ /pubmed/19095761 http://dx.doi.org/10.2337/db08-0585 Text en Copyright © 2009, 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 | Signal Transduction Mantovani, Giovanna Bondioni, Sara Alberti, Luisella Gilardini, Luisa Invitti, Cecilia Corbetta, Sabrina Zappa, Marco A. Ferrero, Stefano Lania, Andrea G. Bosari, Silvano Beck-Peccoz, Paolo Spada, Anna Protein Kinase A Regulatory Subunits in Human Adipose Tissue: Decreased R2B Expression and Activity in Adipocytes From Obese Subjects |
title | Protein Kinase A Regulatory Subunits in Human Adipose Tissue: Decreased R2B Expression and Activity in Adipocytes From Obese Subjects |
title_full | Protein Kinase A Regulatory Subunits in Human Adipose Tissue: Decreased R2B Expression and Activity in Adipocytes From Obese Subjects |
title_fullStr | Protein Kinase A Regulatory Subunits in Human Adipose Tissue: Decreased R2B Expression and Activity in Adipocytes From Obese Subjects |
title_full_unstemmed | Protein Kinase A Regulatory Subunits in Human Adipose Tissue: Decreased R2B Expression and Activity in Adipocytes From Obese Subjects |
title_short | Protein Kinase A Regulatory Subunits in Human Adipose Tissue: Decreased R2B Expression and Activity in Adipocytes From Obese Subjects |
title_sort | protein kinase a regulatory subunits in human adipose tissue: decreased r2b expression and activity in adipocytes from obese subjects |
topic | Signal Transduction |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2646060/ https://www.ncbi.nlm.nih.gov/pubmed/19095761 http://dx.doi.org/10.2337/db08-0585 |
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