ECE2007 Poster Presentations (1) (659 abstracts)
Expression of PKA regulatory subunits inversely correlates with BMI and insulin resistance parameters in human adipocytes from lean and obese subjects
Sara Bondioni 1 , Giovanna Mantovani 1 , Luisella Alberti 2 , Sabrina Corbetta 3 , Luisa Gilardini 2 , Cecilia Invitti 2 , Marco Antonio Zappa 4 , Stefano Ferrero 5 , Erika Peverelli 1 , Andrea G Lania 1 , Paolo Beck-Peccoz 1 & Anna Spada 1
1Endocrine Unit, Dpt. of Medical Sciences, Fondazione Ospedale Maggiore Policlinico Mangiagalli e Regina Elena IRCCS, University of Milan, Milan, Italy; 2Lab. of Diabetologic Research, Istituto Auxologico Italiano IRCCS, Milan, Italy; 3Endocrinology and Diabetology Unit, Dpt. of Medical-Surgical Sciences, University of Milan, Policlinico San Donato IRCCS, San Donato Milanese, Milan, Italy; 4General Surgery Unit, Dpt. of Surgical Sciences, University of Milan, Fondazione Ospedale Maggiore Policlinico Mangiagalli e Regina Elena IRCCS, Milan, Italy; 5Pathology Unit, Department of Medicine, Surgery and Dentistry, A.O. San Paolo and Fondazione Ospedale Maggiore Policlinico Mangiagalli e Regina Elena IRCCS, Milan, Italy.
In human adipocytes the cAMP-dependent pathway mediates signals originating from the activation of beta-adrenergic receptors, thus playing a key role in the regulation of important metabolic processes such as lipolysis and thermogenesis. CyclicAMP effects are mainly mediated by cAMP-dependent protein kinase (PKA), a tetrameric enzyme composed by two catalytic subunits associated with two regulatory (R) subunits. There are four different R subunit genes and proteins (R1A, R1B, R2A, R2B) expressed with a tissue-specific pattern and exerting distinct roles in cell differentiation and growth control. Recent studies indicate the R2B isoform as the most expressed in mouse adipose tissue while its presence is limited elsewhere. Moreover, R2B knock-out mice are genetically lean and protected against developing diet-induced obesity and fatty-livers. The aim of this study was to investigate the expression of the different PKA regulatory subunits in 65 human subcutaneous and visceral adipose tissue samples from 10 lean subjects (BMI<25) and 55 obese patients (BMI>30). Real-time PCR showed that, as in mice, R2B is the most abundant transcript, both in obese and normal subjects, with no differences between visceral and subcutaneous adipose tissue. Moreover, a significant negative correlation was observed between R2B expression levels and BMI, insulin levels, HOMA-IR (r=−0.280, r=−0.269, r=−0.255, respectively; P<0.05), with a positive correlation with adiponectin and adiponectin receptors 1&2 mRNA levels (r=+0.636, r=+0.582, r=+0.631 respectively; P<0.001). Moreover, among obese patients, patients with metabolic syndrome showed the lowest R2B levels. Immunohystochemistry and western-blot analysis performed in 15 of the 55 samples from obese patients and in the 10 samples from lean subjects confirmed the same expression pattern. This is the first study evaluating the relative expression of the different PKA isoforms in human adipose tissue. Our results indicating important BMI-related differences in R2B expression suggest that similar differences in PKA activity may modulate the lipolytic response to beta-adrenergic activation.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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