Attenuation of age-related metabolic dysfunction in mice with a targeted disruption of the Cbeta subunit of protein kinase A
The cyclic adenosine monophosphate-dependent protein kinase A (PKA) pathway helps regulate both cell growth and division, and triglyceride storage and metabolism in response to nutrient status. Studies in yeast show that disruption of this pathway promotes longevity in a manner similar to caloric re...
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Veröffentlicht in: | The journals of gerontology. Series A, Biological sciences and medical sciences Biological sciences and medical sciences, 2009-12, Vol.64 (12), p.1221 |
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container_title | The journals of gerontology. Series A, Biological sciences and medical sciences |
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creator | Enns, Linda C Morton, John F Mangalindan, Ruby Sue McKnight, G Stanley Schwartz, Michael W Kaeberlein, Matt R Kennedy, Brian K Rabinovitch, Peter S Ladiges, Warren C |
description | The cyclic adenosine monophosphate-dependent protein kinase A (PKA) pathway helps regulate both cell growth and division, and triglyceride storage and metabolism in response to nutrient status. Studies in yeast show that disruption of this pathway promotes longevity in a manner similar to caloric restriction. Because PKA is highly conserved, it can be studied in mammalian systems. This report describes the metabolic phenotype of mice lacking the PKA catalytic subunit Cbeta. We confirmed that Cbeta has high levels of expression in the brain but also showed moderate levels in liver. Cbeta-null animals had reduced basal PKA activity while appearing overtly normal when fed standard rodent chow. However, the absence of Cbeta protected mice from diet-induced obesity, steatosis, dyslipoproteinemia, and insulin resistance, without any differences in caloric intake or locomotor activity. These findings have relevant pharmacological implications because aging in mammals is characterized by metabolic decline associated with obesity, altered body fat distribution, and insulin resistance. |
doi_str_mv | 10.1093/gerona/glp133 |
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Series A, Biological sciences and medical sciences</title><addtitle>J Gerontol A Biol Sci Med Sci</addtitle><description>The cyclic adenosine monophosphate-dependent protein kinase A (PKA) pathway helps regulate both cell growth and division, and triglyceride storage and metabolism in response to nutrient status. Studies in yeast show that disruption of this pathway promotes longevity in a manner similar to caloric restriction. Because PKA is highly conserved, it can be studied in mammalian systems. This report describes the metabolic phenotype of mice lacking the PKA catalytic subunit Cbeta. We confirmed that Cbeta has high levels of expression in the brain but also showed moderate levels in liver. Cbeta-null animals had reduced basal PKA activity while appearing overtly normal when fed standard rodent chow. However, the absence of Cbeta protected mice from diet-induced obesity, steatosis, dyslipoproteinemia, and insulin resistance, without any differences in caloric intake or locomotor activity. These findings have relevant pharmacological implications because aging in mammals is characterized by metabolic decline associated with obesity, altered body fat distribution, and insulin resistance.</description><subject>Aging - genetics</subject><subject>Aging - metabolism</subject><subject>Animals</subject><subject>Blood Glucose - metabolism</subject><subject>Body Composition - genetics</subject><subject>Cyclic AMP-Dependent Protein Kinase Catalytic Subunits - deficiency</subject><subject>Cyclic AMP-Dependent Protein Kinase Catalytic Subunits - metabolism</subject><subject>Dietary Carbohydrates - adverse effects</subject><subject>Dietary Fats - adverse effects</subject><subject>Disease Models, Animal</subject><subject>Immunoblotting</subject><subject>Insulin Resistance</subject><subject>Lipid Metabolism - physiology</subject><subject>Longevity</subject><subject>Metabolic Syndrome - genetics</subject><subject>Metabolic Syndrome - metabolism</subject><subject>Metabolic Syndrome - physiopathology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Obesity - genetics</subject><subject>Obesity - metabolism</subject><subject>Obesity - physiopathology</subject><subject>Probability</subject><subject>Random Allocation</subject><subject>Signal Transduction</subject><issn>1758-535X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kMtKw0AUhgdBbK0u3cq8QGzm2mRZijcouOnCXZnLmXQ0mYSZCVLw4W3Uns2Bw_d_cH6E7kj5QMqaLRuIfVDLph0IYxdoTlaiKgQT7zN0ndJHOY2gV2hG6tVKUlLN0fc6Zwijyr4PuHdYNVBEaFUGizvISvetN9gekxuD-YV8wJ03gL98PmCFs4oNTLT1KY7D2ZMPgDf6JMBp1GPweToOsc9wyn_6oBLg9Q26dKpNcPu_F2j39LjbvBTbt-fXzXpbDOL0gFGVlJQrXlHNmSLOcMOAu5orWklOKS-pkJYIK4211GlNLaW2hFpyq6VjC3T_px1G3YHdD9F3Kh735xbYD2xPYGw</recordid><startdate>200912</startdate><enddate>200912</enddate><creator>Enns, Linda C</creator><creator>Morton, John F</creator><creator>Mangalindan, Ruby Sue</creator><creator>McKnight, G Stanley</creator><creator>Schwartz, Michael W</creator><creator>Kaeberlein, Matt R</creator><creator>Kennedy, Brian K</creator><creator>Rabinovitch, Peter S</creator><creator>Ladiges, Warren C</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>200912</creationdate><title>Attenuation of age-related metabolic dysfunction in mice with a targeted disruption of the Cbeta subunit of protein kinase A</title><author>Enns, Linda C ; Morton, John F ; Mangalindan, Ruby Sue ; McKnight, G Stanley ; Schwartz, Michael W ; Kaeberlein, Matt R ; Kennedy, Brian K ; Rabinovitch, Peter S ; Ladiges, Warren C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p558-ca86624a482b43a1fc4c3e4f94a28642240256d15d6cdd2fbb2d22d0e964db6f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Aging - genetics</topic><topic>Aging - metabolism</topic><topic>Animals</topic><topic>Blood Glucose - metabolism</topic><topic>Body Composition - genetics</topic><topic>Cyclic AMP-Dependent Protein Kinase Catalytic Subunits - deficiency</topic><topic>Cyclic AMP-Dependent Protein Kinase Catalytic Subunits - metabolism</topic><topic>Dietary Carbohydrates - adverse effects</topic><topic>Dietary Fats - adverse effects</topic><topic>Disease Models, Animal</topic><topic>Immunoblotting</topic><topic>Insulin Resistance</topic><topic>Lipid Metabolism - physiology</topic><topic>Longevity</topic><topic>Metabolic Syndrome - genetics</topic><topic>Metabolic Syndrome - metabolism</topic><topic>Metabolic Syndrome - physiopathology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Obesity - genetics</topic><topic>Obesity - metabolism</topic><topic>Obesity - physiopathology</topic><topic>Probability</topic><topic>Random Allocation</topic><topic>Signal Transduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Enns, Linda C</creatorcontrib><creatorcontrib>Morton, John F</creatorcontrib><creatorcontrib>Mangalindan, Ruby Sue</creatorcontrib><creatorcontrib>McKnight, G Stanley</creatorcontrib><creatorcontrib>Schwartz, Michael W</creatorcontrib><creatorcontrib>Kaeberlein, Matt R</creatorcontrib><creatorcontrib>Kennedy, Brian K</creatorcontrib><creatorcontrib>Rabinovitch, Peter S</creatorcontrib><creatorcontrib>Ladiges, Warren C</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>The journals of gerontology. 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Series A, Biological sciences and medical sciences</jtitle><addtitle>J Gerontol A Biol Sci Med Sci</addtitle><date>2009-12</date><risdate>2009</risdate><volume>64</volume><issue>12</issue><spage>1221</spage><pages>1221-</pages><eissn>1758-535X</eissn><abstract>The cyclic adenosine monophosphate-dependent protein kinase A (PKA) pathway helps regulate both cell growth and division, and triglyceride storage and metabolism in response to nutrient status. Studies in yeast show that disruption of this pathway promotes longevity in a manner similar to caloric restriction. Because PKA is highly conserved, it can be studied in mammalian systems. This report describes the metabolic phenotype of mice lacking the PKA catalytic subunit Cbeta. We confirmed that Cbeta has high levels of expression in the brain but also showed moderate levels in liver. Cbeta-null animals had reduced basal PKA activity while appearing overtly normal when fed standard rodent chow. However, the absence of Cbeta protected mice from diet-induced obesity, steatosis, dyslipoproteinemia, and insulin resistance, without any differences in caloric intake or locomotor activity. These findings have relevant pharmacological implications because aging in mammals is characterized by metabolic decline associated with obesity, altered body fat distribution, and insulin resistance.</abstract><cop>United States</cop><pmid>19776218</pmid><doi>10.1093/gerona/glp133</doi></addata></record> |
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source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection |
subjects | Aging - genetics Aging - metabolism Animals Blood Glucose - metabolism Body Composition - genetics Cyclic AMP-Dependent Protein Kinase Catalytic Subunits - deficiency Cyclic AMP-Dependent Protein Kinase Catalytic Subunits - metabolism Dietary Carbohydrates - adverse effects Dietary Fats - adverse effects Disease Models, Animal Immunoblotting Insulin Resistance Lipid Metabolism - physiology Longevity Metabolic Syndrome - genetics Metabolic Syndrome - metabolism Metabolic Syndrome - physiopathology Mice Mice, Inbred C57BL Obesity - genetics Obesity - metabolism Obesity - physiopathology Probability Random Allocation Signal Transduction |
title | Attenuation of age-related metabolic dysfunction in mice with a targeted disruption of the Cbeta subunit of protein kinase A |
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