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Differentially Regulated Protein Kinase A (PKA) Activity in Adipose Tissue and Liver Is Associated With Resistance to Diet-Induced Obesity and Glucose Intolerance in Mice That Lack PKA Regulatory Subunit Type IIα

The cAMP-dependent protein kinase A (PKA) signaling system is widely expressed and has a central role in regulating cellular metabolism in all organ systems affected by obesity. PKA has four regulatory (RIα, RIIα, RIβ, RIIβ) and four catalytic (Cα, Cβ, Cγ, Prkx) subunit isoforms that have tissue-spe... Full description

Journal Title: Endocrinology (Philadelphia) 2014-09, Vol.155 (9), p.3397-3408
Main Author: London, Edra
Other Authors: Nesterova, Maria , Sinaii, Ninet , Szarek, Eva , Chanturiya, Tatyana , Mastroyannis, Spyridon A , Gavrilova, Oksana , Stratakis, Constantine A
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: United States: Endocrine Society
ID: ISSN: 0013-7227
Link: https://www.ncbi.nlm.nih.gov/pubmed/24914943
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recordid: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4138573
title: Differentially Regulated Protein Kinase A (PKA) Activity in Adipose Tissue and Liver Is Associated With Resistance to Diet-Induced Obesity and Glucose Intolerance in Mice That Lack PKA Regulatory Subunit Type IIα
format: Article
creator:
  • London, Edra
  • Nesterova, Maria
  • Sinaii, Ninet
  • Szarek, Eva
  • Chanturiya, Tatyana
  • Mastroyannis, Spyridon A
  • Gavrilova, Oksana
  • Stratakis, Constantine A
subjects:
  • Abridged Index Medicus
  • Adipose Tissue - enzymology
  • Adipose Tissue - metabolism
  • Animals
  • Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit - deficiency
  • Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit - genetics
  • Cyclic AMP-Dependent Protein Kinases - genetics
  • Cyclic AMP-Dependent Protein Kinases - metabolism
  • Diet, High-Fat - adverse effects
  • Energy Balance
  • Energy Balance-Obesity
  • Fatty Liver - enzymology
  • Fatty Liver - genetics
  • Fatty Liver - prevention & control
  • Female
  • Glucose Intolerance - enzymology
  • Glucose Intolerance - genetics
  • Glucose Intolerance - prevention & control
  • Humans
  • Liver - enzymology
  • Liver - metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Non-alcoholic Fatty Liver Disease
  • Obesity
  • Obesity - enzymology
  • Obesity - genetics
  • Obesity - prevention & control
ispartof: Endocrinology (Philadelphia), 2014-09, Vol.155 (9), p.3397-3408
description: The cAMP-dependent protein kinase A (PKA) signaling system is widely expressed and has a central role in regulating cellular metabolism in all organ systems affected by obesity. PKA has four regulatory (RIα, RIIα, RIβ, RIIβ) and four catalytic (Cα, Cβ, Cγ, Prkx) subunit isoforms that have tissue-specific expression profiles. In mice, knockout (KO) of RIIβ, the primary PKA regulatory subunit in adipose tissue or knockout of the catalytic subunit Cβ resulted in a lean phenotype that resists diet-induced obesity and associated metabolic complications. Here we report that the disruption of the ubiquitously expressed PKA RIIα subunit in mice (RIIαKO) confers resistance to diet-induced obesity, glucose intolerance, and hepatic steatosis. After 2-week high-fat diet exposure, RIIαKO mice weighed less than wild-type littermates. Over time this effect was more pronounced in female mice that were also leaner than their wild-type counterparts, regardless of the diet. Decreased intake of a high-fat diet contributed to the attenuated weight gain in RIIαKO mice. Additionally, RIIα deficiency caused differential regulation of PKA in key metabolic organs: cAMP-stimulated PKA activity was decreased in liver and increased in gonadal adipose tissue. We conclude that RIIα represents a potential target for therapeutic interventions in obesity, glucose intolerance, and nonalcoholic fatty liver disease.
language: eng
source:
identifier: ISSN: 0013-7227
fulltext: no_fulltext
issn:
  • 0013-7227
  • 1945-7170
url: Link


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titleDifferentially Regulated Protein Kinase A (PKA) Activity in Adipose Tissue and Liver Is Associated With Resistance to Diet-Induced Obesity and Glucose Intolerance in Mice That Lack PKA Regulatory Subunit Type IIα
creatorLondon, Edra ; Nesterova, Maria ; Sinaii, Ninet ; Szarek, Eva ; Chanturiya, Tatyana ; Mastroyannis, Spyridon A ; Gavrilova, Oksana ; Stratakis, Constantine A
creatorcontribLondon, Edra ; Nesterova, Maria ; Sinaii, Ninet ; Szarek, Eva ; Chanturiya, Tatyana ; Mastroyannis, Spyridon A ; Gavrilova, Oksana ; Stratakis, Constantine A
descriptionThe cAMP-dependent protein kinase A (PKA) signaling system is widely expressed and has a central role in regulating cellular metabolism in all organ systems affected by obesity. PKA has four regulatory (RIα, RIIα, RIβ, RIIβ) and four catalytic (Cα, Cβ, Cγ, Prkx) subunit isoforms that have tissue-specific expression profiles. In mice, knockout (KO) of RIIβ, the primary PKA regulatory subunit in adipose tissue or knockout of the catalytic subunit Cβ resulted in a lean phenotype that resists diet-induced obesity and associated metabolic complications. Here we report that the disruption of the ubiquitously expressed PKA RIIα subunit in mice (RIIαKO) confers resistance to diet-induced obesity, glucose intolerance, and hepatic steatosis. After 2-week high-fat diet exposure, RIIαKO mice weighed less than wild-type littermates. Over time this effect was more pronounced in female mice that were also leaner than their wild-type counterparts, regardless of the diet. Decreased intake of a high-fat diet contributed to the attenuated weight gain in RIIαKO mice. Additionally, RIIα deficiency caused differential regulation of PKA in key metabolic organs: cAMP-stimulated PKA activity was decreased in liver and increased in gonadal adipose tissue. We conclude that RIIα represents a potential target for therapeutic interventions in obesity, glucose intolerance, and nonalcoholic fatty liver disease.
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subjectAbridged Index Medicus ; Adipose Tissue - enzymology ; Adipose Tissue - metabolism ; Animals ; Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit - deficiency ; Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit - genetics ; Cyclic AMP-Dependent Protein Kinases - genetics ; Cyclic AMP-Dependent Protein Kinases - metabolism ; Diet, High-Fat - adverse effects ; Energy Balance ; Energy Balance-Obesity ; Fatty Liver - enzymology ; Fatty Liver - genetics ; Fatty Liver - prevention & control ; Female ; Glucose Intolerance - enzymology ; Glucose Intolerance - genetics ; Glucose Intolerance - prevention & control ; Humans ; Liver - enzymology ; Liver - metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Non-alcoholic Fatty Liver Disease ; Obesity ; Obesity - enzymology ; Obesity - genetics ; Obesity - prevention & control
ispartofEndocrinology (Philadelphia), 2014-09, Vol.155 (9), p.3397-3408
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1Nesterova, Maria
2Sinaii, Ninet
3Szarek, Eva
4Chanturiya, Tatyana
5Mastroyannis, Spyridon A
6Gavrilova, Oksana
7Stratakis, Constantine A
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0Differentially Regulated Protein Kinase A (PKA) Activity in Adipose Tissue and Liver Is Associated With Resistance to Diet-Induced Obesity and Glucose Intolerance in Mice That Lack PKA Regulatory Subunit Type IIα
1Endocrinology (Philadelphia)
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descriptionThe cAMP-dependent protein kinase A (PKA) signaling system is widely expressed and has a central role in regulating cellular metabolism in all organ systems affected by obesity. PKA has four regulatory (RIα, RIIα, RIβ, RIIβ) and four catalytic (Cα, Cβ, Cγ, Prkx) subunit isoforms that have tissue-specific expression profiles. In mice, knockout (KO) of RIIβ, the primary PKA regulatory subunit in adipose tissue or knockout of the catalytic subunit Cβ resulted in a lean phenotype that resists diet-induced obesity and associated metabolic complications. Here we report that the disruption of the ubiquitously expressed PKA RIIα subunit in mice (RIIαKO) confers resistance to diet-induced obesity, glucose intolerance, and hepatic steatosis. After 2-week high-fat diet exposure, RIIαKO mice weighed less than wild-type littermates. Over time this effect was more pronounced in female mice that were also leaner than their wild-type counterparts, regardless of the diet. Decreased intake of a high-fat diet contributed to the attenuated weight gain in RIIαKO mice. Additionally, RIIα deficiency caused differential regulation of PKA in key metabolic organs: cAMP-stimulated PKA activity was decreased in liver and increased in gonadal adipose tissue. We conclude that RIIα represents a potential target for therapeutic interventions in obesity, glucose intolerance, and nonalcoholic fatty liver disease.
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1Adipose Tissue - enzymology
2Adipose Tissue - metabolism
3Animals
4Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit - deficiency
5Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit - genetics
6Cyclic AMP-Dependent Protein Kinases - genetics
7Cyclic AMP-Dependent Protein Kinases - metabolism
8Diet, High-Fat - adverse effects
9Energy Balance
10Energy Balance-Obesity
11Fatty Liver - enzymology
12Fatty Liver - genetics
13Fatty Liver - prevention & control
14Female
15Glucose Intolerance - enzymology
16Glucose Intolerance - genetics
17Glucose Intolerance - prevention & control
18Humans
19Liver - enzymology
20Liver - metabolism
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24Mice, Knockout
25Non-alcoholic Fatty Liver Disease
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29Obesity - prevention & control
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titleDifferentially Regulated Protein Kinase A (PKA) Activity in Adipose Tissue and Liver Is Associated With Resistance to Diet-Induced Obesity and Glucose Intolerance in Mice That Lack PKA Regulatory Subunit Type IIα
authorLondon, Edra ; Nesterova, Maria ; Sinaii, Ninet ; Szarek, Eva ; Chanturiya, Tatyana ; Mastroyannis, Spyridon A ; Gavrilova, Oksana ; Stratakis, Constantine A
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1Adipose Tissue - enzymology
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3Animals
4Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit - deficiency
5Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit - genetics
6Cyclic AMP-Dependent Protein Kinases - genetics
7Cyclic AMP-Dependent Protein Kinases - metabolism
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9Energy Balance
10Energy Balance-Obesity
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13Fatty Liver - prevention & control
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atitleDifferentially Regulated Protein Kinase A (PKA) Activity in Adipose Tissue and Liver Is Associated With Resistance to Diet-Induced Obesity and Glucose Intolerance in Mice That Lack PKA Regulatory Subunit Type IIα
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notesThis work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
abstractThe cAMP-dependent protein kinase A (PKA) signaling system is widely expressed and has a central role in regulating cellular metabolism in all organ systems affected by obesity. PKA has four regulatory (RIα, RIIα, RIβ, RIIβ) and four catalytic (Cα, Cβ, Cγ, Prkx) subunit isoforms that have tissue-specific expression profiles. In mice, knockout (KO) of RIIβ, the primary PKA regulatory subunit in adipose tissue or knockout of the catalytic subunit Cβ resulted in a lean phenotype that resists diet-induced obesity and associated metabolic complications. Here we report that the disruption of the ubiquitously expressed PKA RIIα subunit in mice (RIIαKO) confers resistance to diet-induced obesity, glucose intolerance, and hepatic steatosis. After 2-week high-fat diet exposure, RIIαKO mice weighed less than wild-type littermates. Over time this effect was more pronounced in female mice that were also leaner than their wild-type counterparts, regardless of the diet. Decreased intake of a high-fat diet contributed to the attenuated weight gain in RIIαKO mice. Additionally, RIIα deficiency caused differential regulation of PKA in key metabolic organs: cAMP-stimulated PKA activity was decreased in liver and increased in gonadal adipose tissue. We conclude that RIIα represents a potential target for therapeutic interventions in obesity, glucose intolerance, and nonalcoholic fatty liver disease.
copUnited States
pubEndocrine Society
pmid24914943
doi10.1210/en.2014-1122
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