Protein Kinase A Regulatory Subunits in Human Adipose Tissue

Decreased R2B Expression and Activity in Adipocytes From Obese Subjects

  1. Giovanna Mantovani1,
  2. Sara Bondioni1,
  3. Luisella Alberti2,
  4. Luisa Gilardini2,
  5. Cecilia Invitti2,
  6. Sabrina Corbetta3,
  7. Marco A. Zappa4,
  8. Stefano Ferrero5,
  9. Andrea G. Lania1,
  10. Silvano Bosari5,
  11. Paolo Beck-Peccoz1 and
  12. Anna Spada1
  1. 1Endocrine Unit, Department of Medical Sciences, University of Milan, Fondazione Ospedale Maggiore Policlinico IRCCS, Milan, Italy
  2. 2Unit for Metabolic Diseases and Diabetes, Istituto Auxologico Italiano IRCCS, Milan, Italy
  3. 3Endocrinology and Diabetology Unit, Department of Medical-Surgical Sciences, University of Milan, Policlinico San Donato IRCCS, Milan, Italy
  4. 4Department of Surgical Sciences, Fondazione Ospedale Maggiore Policlinico IRCCS, Milan, Italy
  5. 5Pathology Unit, Department of Medicine, Surgery and Dentistry, A.O. San Paolo and Fondazione Ospedale Maggiore IRCCS, Milan, Italy
  1. 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 is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted December 5, 2008.
    • Received April 30, 2008.
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  1. Diabetes vol. 58 no. 3 620-626
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