Protein kinase A regulatory subunits in human adipose tissue: Decreased R2B expression and activity in adipocytes from obese subjects

Giovanna Mantovani, Sara Bondioni, Luisella Alberti, Luisa Gilardini, Cecilia Invitti, Sabrina Corbetta, Marco A. Zappa, Stefano Ferrero, Andrea G. Lania, Silvano Bosari, Paolo Beck-Peccoz, Anna Spada

Research output: Contribution to journalArticle

20 Citations (Scopus)

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 lipoly- sis in adipose tissues from obese and nonobese subjects. RESEARCH DESIGN AND METHODS-The expression of the different PKA regulatory subunits was evaluated by immuno- histochemistry, 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.

Original languageEnglish
Pages (from-to)620-626
Number of pages7
JournalDiabetes
Volume58
Issue number3
DOIs
Publication statusPublished - Mar 2009

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Cyclic AMP-Dependent Protein Kinases
Adipocytes
Adipose Tissue
Intra-Abdominal Fat
Lipolysis
Subcutaneous Fat
Adrenergic Agents
Glycerol
Obesity
Messenger RNA
Proteins
Thermogenesis
Waist Circumference
Fatty Liver
Cyclic AMP
Insulin Resistance
Real-Time Polymerase Chain Reaction
Signal Transduction
Protein Isoforms
Homeostasis

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

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.

In: Diabetes, Vol. 58, No. 3, 03.2009, p. 620-626.

Research output: Contribution to journalArticle

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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 lipoly- sis in adipose tissues from obese and nonobese subjects. RESEARCH DESIGN AND METHODS-The expression of the different PKA regulatory subunits was evaluated by immuno- histochemistry, 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.",
author = "Giovanna Mantovani and Sara Bondioni and Luisella Alberti and Luisa Gilardini and Cecilia Invitti and Sabrina Corbetta and Zappa, {Marco A.} and Stefano Ferrero and Lania, {Andrea G.} and Silvano Bosari and Paolo Beck-Peccoz and Anna Spada",
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AU - Mantovani, Giovanna

AU - Bondioni, Sara

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AU - Gilardini, Luisa

AU - Invitti, Cecilia

AU - Corbetta, Sabrina

AU - Zappa, Marco A.

AU - Ferrero, Stefano

AU - Lania, Andrea G.

AU - Bosari, Silvano

AU - Beck-Peccoz, Paolo

AU - Spada, Anna

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N2 - 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 lipoly- sis in adipose tissues from obese and nonobese subjects. RESEARCH DESIGN AND METHODS-The expression of the different PKA regulatory subunits was evaluated by immuno- histochemistry, 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.

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