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 language | English |
|---|---|
| Pages (from-to) | 620-626 |
| Number of pages | 7 |
| Journal | Diabetes |
| Volume | 58 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 2009 |
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ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
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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 journal › Article
}
TY - JOUR
T1 - Protein kinase A regulatory subunits in human adipose tissue
T2 - Decreased R2B expression and activity in adipocytes from obese subjects
AU - Mantovani, Giovanna
AU - Bondioni, Sara
AU - Alberti, Luisella
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
PY - 2009/3
Y1 - 2009/3
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.
AB - 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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U2 - 10.2337/db08-0585
DO - 10.2337/db08-0585
M3 - Article
C2 - 19095761
AN - SCOPUS:62749164774
VL - 58
SP - 620
EP - 626
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 3
ER -