Protein Kinase A Regulatory Subunits in Human Adipose Tissue
Decreased R2B Expression and Activity in Adipocytes From Obese Subjects
Giovanna Mantovani 1 ,
Sara Bondioni 1 ,
Luisella Alberti 2 ,
Luisa Gilardini 2 ,
Cecilia Invitti 2 ,
Sabrina Corbetta 3 ,
Marco A. Zappa 4 ,
Stefano Ferrero 5 ,
Andrea G. Lania 1 ,
Silvano Bosari 5 ,
Paolo Beck-Peccoz 1 and
Anna Spada 1
1 Endocrine Unit, Department of Medical Sciences, University of Milan, Fondazione Ospedale Maggiore Policlinico IRCCS, Milan,
Italy
2 Unit for Metabolic Diseases and Diabetes, Istituto Auxologico Italiano IRCCS, Milan, Italy
3 Endocrinology and Diabetology Unit, Department of Medical-Surgical Sciences, University of Milan, Policlinico San Donato IRCCS,
Milan, Italy
4 Department of Surgical Sciences, Fondazione Ospedale Maggiore Policlinico IRCCS, Milan, Italy
5 Pathology Unit, Department of Medicine, Surgery and Dentistry, A.O. San Paolo and Fondazione Ospedale Maggiore IRCCS, Milan,
Italy
Corresponding author: Giovanna Mantovani, giovanna.mantovani{at}unimi.it
Abstract
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.
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 18 December 2008.
G.M. and S.B. contributed equally to this work.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work
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10.2337/db08-0585