Carbonyl reductase 1 amplifies glucocorticoid action in adipose tissue and impairs glucose tolerance in lean mice
Objective: Carbonyl reductase 1 (Cbr1), a recently discovered contributor to tissue glucocorticoid metabolism converting corticosterone to 20β-dihydrocorticosterone (20β-DHB), is upregulated in adipose tissue of obese humans and mice and may contribute to cardiometabolic complications of obesity. Th...
Ausführliche Beschreibung
Autor*in: |
Rachel M.B. Bell [verfasserIn] Elisa Villalobos [verfasserIn] Mark Nixon [verfasserIn] Allende Miguelez-Crespo [verfasserIn] Lee Murphy [verfasserIn] Angie Fawkes [verfasserIn] Audrey Coutts [verfasserIn] Matthew G.F. Sharp [verfasserIn] Martha V. Koerner [verfasserIn] Emma Allan [verfasserIn] Onno C. Meijer [verfasserIn] Renè Houtman [verfasserIn] Alex Odermatt [verfasserIn] Katharina R. Beck [verfasserIn] Scott G. Denham [verfasserIn] Patricia Lee [verfasserIn] Natalie Z.M. Homer [verfasserIn] Brian R. Walker [verfasserIn] Ruth A. Morgan [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2021 |
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Übergeordnetes Werk: |
In: Molecular Metabolism - Elsevier, 2015, 48(2021), Seite 101225- |
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Übergeordnetes Werk: |
volume:48 ; year:2021 ; pages:101225- |
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DOI / URN: |
10.1016/j.molmet.2021.101225 |
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Katalog-ID: |
DOAJ001324942 |
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245 | 1 | 0 | |a Carbonyl reductase 1 amplifies glucocorticoid action in adipose tissue and impairs glucose tolerance in lean mice |
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520 | |a Objective: Carbonyl reductase 1 (Cbr1), a recently discovered contributor to tissue glucocorticoid metabolism converting corticosterone to 20β-dihydrocorticosterone (20β-DHB), is upregulated in adipose tissue of obese humans and mice and may contribute to cardiometabolic complications of obesity. This study tested the hypothesis that Cbr1-mediated glucocorticoid metabolism influences glucocorticoid and mineralocorticoid receptor activation in adipose tissue and impacts glucose homeostasis in lean and obese states. Methods: The actions of 20β-DHB on corticosteroid receptors in adipose tissue were investigated first using a combination of in silico, in vitro, and transcriptomic techniques and then in vivo administration in combination with receptor antagonists. Mice lacking one Cbr1 allele and mice overexpressing Cbr1 in their adipose tissue underwent metabolic phenotyping before and after induction of obesity with high-fat feeding. Results: 20β-DHB activated both the glucocorticoid and mineralocorticoid receptor in adipose tissue and systemic administration to wild-type mice induced glucose intolerance, an effect that was ameliorated by both glucocorticoid and mineralocorticoid receptor antagonism. Cbr1 haploinsufficient lean male mice had lower fasting glucose and improved glucose tolerance compared with littermate controls, a difference that was abolished by administration of 20β-DHB and absent in female mice with higher baseline adipose 20β-DHB concentrations than male mice. Conversely, overexpression of Cbr1 in adipose tissue resulted in worsened glucose tolerance and higher fasting glucose in lean male and female mice. However, neither Cbr1 haploinsfficiency nor adipose overexpression affected glucose dyshomeostasis induced by high-fat feeding. Conclusions: Carbonyl reductase 1 is a novel regulator of glucocorticoid and mineralocorticoid receptor activation in adipose tissue that influences glucose homeostasis in lean mice. | ||
650 | 4 | |a Obesity | |
650 | 4 | |a Glucocorticoid | |
650 | 4 | |a Metabolism | |
650 | 4 | |a Glucose | |
650 | 4 | |a Corticosterone | |
650 | 4 | |a Mineralocorticoid receptor | |
653 | 0 | |a Internal medicine | |
700 | 0 | |a Elisa Villalobos |e verfasserin |4 aut | |
700 | 0 | |a Mark Nixon |e verfasserin |4 aut | |
700 | 0 | |a Allende Miguelez-Crespo |e verfasserin |4 aut | |
700 | 0 | |a Lee Murphy |e verfasserin |4 aut | |
700 | 0 | |a Angie Fawkes |e verfasserin |4 aut | |
700 | 0 | |a Audrey Coutts |e verfasserin |4 aut | |
700 | 0 | |a Matthew G.F. Sharp |e verfasserin |4 aut | |
700 | 0 | |a Martha V. Koerner |e verfasserin |4 aut | |
700 | 0 | |a Emma Allan |e verfasserin |4 aut | |
700 | 0 | |a Onno C. Meijer |e verfasserin |4 aut | |
700 | 0 | |a Renè Houtman |e verfasserin |4 aut | |
700 | 0 | |a Alex Odermatt |e verfasserin |4 aut | |
700 | 0 | |a Katharina R. Beck |e verfasserin |4 aut | |
700 | 0 | |a Scott G. Denham |e verfasserin |4 aut | |
700 | 0 | |a Patricia Lee |e verfasserin |4 aut | |
700 | 0 | |a Natalie Z.M. Homer |e verfasserin |4 aut | |
700 | 0 | |a Brian R. Walker |e verfasserin |4 aut | |
700 | 0 | |a Ruth A. Morgan |e verfasserin |4 aut | |
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10.1016/j.molmet.2021.101225 doi (DE-627)DOAJ001324942 (DE-599)DOAJa6432528238548eaaf19f70db5178bdf DE-627 ger DE-627 rakwb eng RC31-1245 Rachel M.B. Bell verfasserin aut Carbonyl reductase 1 amplifies glucocorticoid action in adipose tissue and impairs glucose tolerance in lean mice 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objective: Carbonyl reductase 1 (Cbr1), a recently discovered contributor to tissue glucocorticoid metabolism converting corticosterone to 20β-dihydrocorticosterone (20β-DHB), is upregulated in adipose tissue of obese humans and mice and may contribute to cardiometabolic complications of obesity. This study tested the hypothesis that Cbr1-mediated glucocorticoid metabolism influences glucocorticoid and mineralocorticoid receptor activation in adipose tissue and impacts glucose homeostasis in lean and obese states. Methods: The actions of 20β-DHB on corticosteroid receptors in adipose tissue were investigated first using a combination of in silico, in vitro, and transcriptomic techniques and then in vivo administration in combination with receptor antagonists. Mice lacking one Cbr1 allele and mice overexpressing Cbr1 in their adipose tissue underwent metabolic phenotyping before and after induction of obesity with high-fat feeding. Results: 20β-DHB activated both the glucocorticoid and mineralocorticoid receptor in adipose tissue and systemic administration to wild-type mice induced glucose intolerance, an effect that was ameliorated by both glucocorticoid and mineralocorticoid receptor antagonism. Cbr1 haploinsufficient lean male mice had lower fasting glucose and improved glucose tolerance compared with littermate controls, a difference that was abolished by administration of 20β-DHB and absent in female mice with higher baseline adipose 20β-DHB concentrations than male mice. Conversely, overexpression of Cbr1 in adipose tissue resulted in worsened glucose tolerance and higher fasting glucose in lean male and female mice. However, neither Cbr1 haploinsfficiency nor adipose overexpression affected glucose dyshomeostasis induced by high-fat feeding. Conclusions: Carbonyl reductase 1 is a novel regulator of glucocorticoid and mineralocorticoid receptor activation in adipose tissue that influences glucose homeostasis in lean mice. Obesity Glucocorticoid Metabolism Glucose Corticosterone Mineralocorticoid receptor Internal medicine Elisa Villalobos verfasserin aut Mark Nixon verfasserin aut Allende Miguelez-Crespo verfasserin aut Lee Murphy verfasserin aut Angie Fawkes verfasserin aut Audrey Coutts verfasserin aut Matthew G.F. Sharp verfasserin aut Martha V. Koerner verfasserin aut Emma Allan verfasserin aut Onno C. Meijer verfasserin aut Renè Houtman verfasserin aut Alex Odermatt verfasserin aut Katharina R. Beck verfasserin aut Scott G. Denham verfasserin aut Patricia Lee verfasserin aut Natalie Z.M. Homer verfasserin aut Brian R. Walker verfasserin aut Ruth A. Morgan verfasserin aut In Molecular Metabolism Elsevier, 2015 48(2021), Seite 101225- (DE-627)739898752 (DE-600)2708735-9 22128778 nnns volume:48 year:2021 pages:101225- https://doi.org/10.1016/j.molmet.2021.101225 kostenfrei https://doaj.org/article/a6432528238548eaaf19f70db5178bdf kostenfrei http://www.sciencedirect.com/science/article/pii/S2212877821000703 kostenfrei https://doaj.org/toc/2212-8778 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 48 2021 101225- |
spelling |
10.1016/j.molmet.2021.101225 doi (DE-627)DOAJ001324942 (DE-599)DOAJa6432528238548eaaf19f70db5178bdf DE-627 ger DE-627 rakwb eng RC31-1245 Rachel M.B. Bell verfasserin aut Carbonyl reductase 1 amplifies glucocorticoid action in adipose tissue and impairs glucose tolerance in lean mice 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objective: Carbonyl reductase 1 (Cbr1), a recently discovered contributor to tissue glucocorticoid metabolism converting corticosterone to 20β-dihydrocorticosterone (20β-DHB), is upregulated in adipose tissue of obese humans and mice and may contribute to cardiometabolic complications of obesity. This study tested the hypothesis that Cbr1-mediated glucocorticoid metabolism influences glucocorticoid and mineralocorticoid receptor activation in adipose tissue and impacts glucose homeostasis in lean and obese states. Methods: The actions of 20β-DHB on corticosteroid receptors in adipose tissue were investigated first using a combination of in silico, in vitro, and transcriptomic techniques and then in vivo administration in combination with receptor antagonists. Mice lacking one Cbr1 allele and mice overexpressing Cbr1 in their adipose tissue underwent metabolic phenotyping before and after induction of obesity with high-fat feeding. Results: 20β-DHB activated both the glucocorticoid and mineralocorticoid receptor in adipose tissue and systemic administration to wild-type mice induced glucose intolerance, an effect that was ameliorated by both glucocorticoid and mineralocorticoid receptor antagonism. Cbr1 haploinsufficient lean male mice had lower fasting glucose and improved glucose tolerance compared with littermate controls, a difference that was abolished by administration of 20β-DHB and absent in female mice with higher baseline adipose 20β-DHB concentrations than male mice. Conversely, overexpression of Cbr1 in adipose tissue resulted in worsened glucose tolerance and higher fasting glucose in lean male and female mice. However, neither Cbr1 haploinsfficiency nor adipose overexpression affected glucose dyshomeostasis induced by high-fat feeding. Conclusions: Carbonyl reductase 1 is a novel regulator of glucocorticoid and mineralocorticoid receptor activation in adipose tissue that influences glucose homeostasis in lean mice. Obesity Glucocorticoid Metabolism Glucose Corticosterone Mineralocorticoid receptor Internal medicine Elisa Villalobos verfasserin aut Mark Nixon verfasserin aut Allende Miguelez-Crespo verfasserin aut Lee Murphy verfasserin aut Angie Fawkes verfasserin aut Audrey Coutts verfasserin aut Matthew G.F. Sharp verfasserin aut Martha V. Koerner verfasserin aut Emma Allan verfasserin aut Onno C. Meijer verfasserin aut Renè Houtman verfasserin aut Alex Odermatt verfasserin aut Katharina R. Beck verfasserin aut Scott G. Denham verfasserin aut Patricia Lee verfasserin aut Natalie Z.M. Homer verfasserin aut Brian R. Walker verfasserin aut Ruth A. Morgan verfasserin aut In Molecular Metabolism Elsevier, 2015 48(2021), Seite 101225- (DE-627)739898752 (DE-600)2708735-9 22128778 nnns volume:48 year:2021 pages:101225- https://doi.org/10.1016/j.molmet.2021.101225 kostenfrei https://doaj.org/article/a6432528238548eaaf19f70db5178bdf kostenfrei http://www.sciencedirect.com/science/article/pii/S2212877821000703 kostenfrei https://doaj.org/toc/2212-8778 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 48 2021 101225- |
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10.1016/j.molmet.2021.101225 doi (DE-627)DOAJ001324942 (DE-599)DOAJa6432528238548eaaf19f70db5178bdf DE-627 ger DE-627 rakwb eng RC31-1245 Rachel M.B. Bell verfasserin aut Carbonyl reductase 1 amplifies glucocorticoid action in adipose tissue and impairs glucose tolerance in lean mice 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objective: Carbonyl reductase 1 (Cbr1), a recently discovered contributor to tissue glucocorticoid metabolism converting corticosterone to 20β-dihydrocorticosterone (20β-DHB), is upregulated in adipose tissue of obese humans and mice and may contribute to cardiometabolic complications of obesity. This study tested the hypothesis that Cbr1-mediated glucocorticoid metabolism influences glucocorticoid and mineralocorticoid receptor activation in adipose tissue and impacts glucose homeostasis in lean and obese states. Methods: The actions of 20β-DHB on corticosteroid receptors in adipose tissue were investigated first using a combination of in silico, in vitro, and transcriptomic techniques and then in vivo administration in combination with receptor antagonists. Mice lacking one Cbr1 allele and mice overexpressing Cbr1 in their adipose tissue underwent metabolic phenotyping before and after induction of obesity with high-fat feeding. Results: 20β-DHB activated both the glucocorticoid and mineralocorticoid receptor in adipose tissue and systemic administration to wild-type mice induced glucose intolerance, an effect that was ameliorated by both glucocorticoid and mineralocorticoid receptor antagonism. Cbr1 haploinsufficient lean male mice had lower fasting glucose and improved glucose tolerance compared with littermate controls, a difference that was abolished by administration of 20β-DHB and absent in female mice with higher baseline adipose 20β-DHB concentrations than male mice. Conversely, overexpression of Cbr1 in adipose tissue resulted in worsened glucose tolerance and higher fasting glucose in lean male and female mice. However, neither Cbr1 haploinsfficiency nor adipose overexpression affected glucose dyshomeostasis induced by high-fat feeding. Conclusions: Carbonyl reductase 1 is a novel regulator of glucocorticoid and mineralocorticoid receptor activation in adipose tissue that influences glucose homeostasis in lean mice. Obesity Glucocorticoid Metabolism Glucose Corticosterone Mineralocorticoid receptor Internal medicine Elisa Villalobos verfasserin aut Mark Nixon verfasserin aut Allende Miguelez-Crespo verfasserin aut Lee Murphy verfasserin aut Angie Fawkes verfasserin aut Audrey Coutts verfasserin aut Matthew G.F. Sharp verfasserin aut Martha V. Koerner verfasserin aut Emma Allan verfasserin aut Onno C. Meijer verfasserin aut Renè Houtman verfasserin aut Alex Odermatt verfasserin aut Katharina R. Beck verfasserin aut Scott G. Denham verfasserin aut Patricia Lee verfasserin aut Natalie Z.M. Homer verfasserin aut Brian R. Walker verfasserin aut Ruth A. Morgan verfasserin aut In Molecular Metabolism Elsevier, 2015 48(2021), Seite 101225- (DE-627)739898752 (DE-600)2708735-9 22128778 nnns volume:48 year:2021 pages:101225- https://doi.org/10.1016/j.molmet.2021.101225 kostenfrei https://doaj.org/article/a6432528238548eaaf19f70db5178bdf kostenfrei http://www.sciencedirect.com/science/article/pii/S2212877821000703 kostenfrei https://doaj.org/toc/2212-8778 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 48 2021 101225- |
allfieldsGer |
10.1016/j.molmet.2021.101225 doi (DE-627)DOAJ001324942 (DE-599)DOAJa6432528238548eaaf19f70db5178bdf DE-627 ger DE-627 rakwb eng RC31-1245 Rachel M.B. Bell verfasserin aut Carbonyl reductase 1 amplifies glucocorticoid action in adipose tissue and impairs glucose tolerance in lean mice 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objective: Carbonyl reductase 1 (Cbr1), a recently discovered contributor to tissue glucocorticoid metabolism converting corticosterone to 20β-dihydrocorticosterone (20β-DHB), is upregulated in adipose tissue of obese humans and mice and may contribute to cardiometabolic complications of obesity. This study tested the hypothesis that Cbr1-mediated glucocorticoid metabolism influences glucocorticoid and mineralocorticoid receptor activation in adipose tissue and impacts glucose homeostasis in lean and obese states. Methods: The actions of 20β-DHB on corticosteroid receptors in adipose tissue were investigated first using a combination of in silico, in vitro, and transcriptomic techniques and then in vivo administration in combination with receptor antagonists. Mice lacking one Cbr1 allele and mice overexpressing Cbr1 in their adipose tissue underwent metabolic phenotyping before and after induction of obesity with high-fat feeding. Results: 20β-DHB activated both the glucocorticoid and mineralocorticoid receptor in adipose tissue and systemic administration to wild-type mice induced glucose intolerance, an effect that was ameliorated by both glucocorticoid and mineralocorticoid receptor antagonism. Cbr1 haploinsufficient lean male mice had lower fasting glucose and improved glucose tolerance compared with littermate controls, a difference that was abolished by administration of 20β-DHB and absent in female mice with higher baseline adipose 20β-DHB concentrations than male mice. Conversely, overexpression of Cbr1 in adipose tissue resulted in worsened glucose tolerance and higher fasting glucose in lean male and female mice. However, neither Cbr1 haploinsfficiency nor adipose overexpression affected glucose dyshomeostasis induced by high-fat feeding. Conclusions: Carbonyl reductase 1 is a novel regulator of glucocorticoid and mineralocorticoid receptor activation in adipose tissue that influences glucose homeostasis in lean mice. Obesity Glucocorticoid Metabolism Glucose Corticosterone Mineralocorticoid receptor Internal medicine Elisa Villalobos verfasserin aut Mark Nixon verfasserin aut Allende Miguelez-Crespo verfasserin aut Lee Murphy verfasserin aut Angie Fawkes verfasserin aut Audrey Coutts verfasserin aut Matthew G.F. Sharp verfasserin aut Martha V. Koerner verfasserin aut Emma Allan verfasserin aut Onno C. Meijer verfasserin aut Renè Houtman verfasserin aut Alex Odermatt verfasserin aut Katharina R. Beck verfasserin aut Scott G. Denham verfasserin aut Patricia Lee verfasserin aut Natalie Z.M. Homer verfasserin aut Brian R. Walker verfasserin aut Ruth A. Morgan verfasserin aut In Molecular Metabolism Elsevier, 2015 48(2021), Seite 101225- (DE-627)739898752 (DE-600)2708735-9 22128778 nnns volume:48 year:2021 pages:101225- https://doi.org/10.1016/j.molmet.2021.101225 kostenfrei https://doaj.org/article/a6432528238548eaaf19f70db5178bdf kostenfrei http://www.sciencedirect.com/science/article/pii/S2212877821000703 kostenfrei https://doaj.org/toc/2212-8778 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 48 2021 101225- |
allfieldsSound |
10.1016/j.molmet.2021.101225 doi (DE-627)DOAJ001324942 (DE-599)DOAJa6432528238548eaaf19f70db5178bdf DE-627 ger DE-627 rakwb eng RC31-1245 Rachel M.B. Bell verfasserin aut Carbonyl reductase 1 amplifies glucocorticoid action in adipose tissue and impairs glucose tolerance in lean mice 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objective: Carbonyl reductase 1 (Cbr1), a recently discovered contributor to tissue glucocorticoid metabolism converting corticosterone to 20β-dihydrocorticosterone (20β-DHB), is upregulated in adipose tissue of obese humans and mice and may contribute to cardiometabolic complications of obesity. This study tested the hypothesis that Cbr1-mediated glucocorticoid metabolism influences glucocorticoid and mineralocorticoid receptor activation in adipose tissue and impacts glucose homeostasis in lean and obese states. Methods: The actions of 20β-DHB on corticosteroid receptors in adipose tissue were investigated first using a combination of in silico, in vitro, and transcriptomic techniques and then in vivo administration in combination with receptor antagonists. Mice lacking one Cbr1 allele and mice overexpressing Cbr1 in their adipose tissue underwent metabolic phenotyping before and after induction of obesity with high-fat feeding. Results: 20β-DHB activated both the glucocorticoid and mineralocorticoid receptor in adipose tissue and systemic administration to wild-type mice induced glucose intolerance, an effect that was ameliorated by both glucocorticoid and mineralocorticoid receptor antagonism. Cbr1 haploinsufficient lean male mice had lower fasting glucose and improved glucose tolerance compared with littermate controls, a difference that was abolished by administration of 20β-DHB and absent in female mice with higher baseline adipose 20β-DHB concentrations than male mice. Conversely, overexpression of Cbr1 in adipose tissue resulted in worsened glucose tolerance and higher fasting glucose in lean male and female mice. However, neither Cbr1 haploinsfficiency nor adipose overexpression affected glucose dyshomeostasis induced by high-fat feeding. Conclusions: Carbonyl reductase 1 is a novel regulator of glucocorticoid and mineralocorticoid receptor activation in adipose tissue that influences glucose homeostasis in lean mice. Obesity Glucocorticoid Metabolism Glucose Corticosterone Mineralocorticoid receptor Internal medicine Elisa Villalobos verfasserin aut Mark Nixon verfasserin aut Allende Miguelez-Crespo verfasserin aut Lee Murphy verfasserin aut Angie Fawkes verfasserin aut Audrey Coutts verfasserin aut Matthew G.F. Sharp verfasserin aut Martha V. Koerner verfasserin aut Emma Allan verfasserin aut Onno C. Meijer verfasserin aut Renè Houtman verfasserin aut Alex Odermatt verfasserin aut Katharina R. Beck verfasserin aut Scott G. Denham verfasserin aut Patricia Lee verfasserin aut Natalie Z.M. Homer verfasserin aut Brian R. Walker verfasserin aut Ruth A. Morgan verfasserin aut In Molecular Metabolism Elsevier, 2015 48(2021), Seite 101225- (DE-627)739898752 (DE-600)2708735-9 22128778 nnns volume:48 year:2021 pages:101225- https://doi.org/10.1016/j.molmet.2021.101225 kostenfrei https://doaj.org/article/a6432528238548eaaf19f70db5178bdf kostenfrei http://www.sciencedirect.com/science/article/pii/S2212877821000703 kostenfrei https://doaj.org/toc/2212-8778 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 48 2021 101225- |
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Bell</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Carbonyl reductase 1 amplifies glucocorticoid action in adipose tissue and impairs glucose tolerance in lean mice</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2021</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Objective: Carbonyl reductase 1 (Cbr1), a recently discovered contributor to tissue glucocorticoid metabolism converting corticosterone to 20β-dihydrocorticosterone (20β-DHB), is upregulated in adipose tissue of obese humans and mice and may contribute to cardiometabolic complications of obesity. This study tested the hypothesis that Cbr1-mediated glucocorticoid metabolism influences glucocorticoid and mineralocorticoid receptor activation in adipose tissue and impacts glucose homeostasis in lean and obese states. Methods: The actions of 20β-DHB on corticosteroid receptors in adipose tissue were investigated first using a combination of in silico, in vitro, and transcriptomic techniques and then in vivo administration in combination with receptor antagonists. Mice lacking one Cbr1 allele and mice overexpressing Cbr1 in their adipose tissue underwent metabolic phenotyping before and after induction of obesity with high-fat feeding. Results: 20β-DHB activated both the glucocorticoid and mineralocorticoid receptor in adipose tissue and systemic administration to wild-type mice induced glucose intolerance, an effect that was ameliorated by both glucocorticoid and mineralocorticoid receptor antagonism. Cbr1 haploinsufficient lean male mice had lower fasting glucose and improved glucose tolerance compared with littermate controls, a difference that was abolished by administration of 20β-DHB and absent in female mice with higher baseline adipose 20β-DHB concentrations than male mice. Conversely, overexpression of Cbr1 in adipose tissue resulted in worsened glucose tolerance and higher fasting glucose in lean male and female mice. However, neither Cbr1 haploinsfficiency nor adipose overexpression affected glucose dyshomeostasis induced by high-fat feeding. 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R - Medicine |
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Rachel M.B. Bell |
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Rachel M.B. Bell misc RC31-1245 misc Obesity misc Glucocorticoid misc Metabolism misc Glucose misc Corticosterone misc Mineralocorticoid receptor misc Internal medicine Carbonyl reductase 1 amplifies glucocorticoid action in adipose tissue and impairs glucose tolerance in lean mice |
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RC31-1245 Carbonyl reductase 1 amplifies glucocorticoid action in adipose tissue and impairs glucose tolerance in lean mice Obesity Glucocorticoid Metabolism Glucose Corticosterone Mineralocorticoid receptor |
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misc RC31-1245 misc Obesity misc Glucocorticoid misc Metabolism misc Glucose misc Corticosterone misc Mineralocorticoid receptor misc Internal medicine |
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misc RC31-1245 misc Obesity misc Glucocorticoid misc Metabolism misc Glucose misc Corticosterone misc Mineralocorticoid receptor misc Internal medicine |
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Carbonyl reductase 1 amplifies glucocorticoid action in adipose tissue and impairs glucose tolerance in lean mice |
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Rachel M.B. Bell Elisa Villalobos Mark Nixon Allende Miguelez-Crespo Lee Murphy Angie Fawkes Audrey Coutts Matthew G.F. Sharp Martha V. Koerner Emma Allan Onno C. Meijer Renè Houtman Alex Odermatt Katharina R. Beck Scott G. Denham Patricia Lee Natalie Z.M. Homer Brian R. Walker Ruth A. Morgan |
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carbonyl reductase 1 amplifies glucocorticoid action in adipose tissue and impairs glucose tolerance in lean mice |
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Carbonyl reductase 1 amplifies glucocorticoid action in adipose tissue and impairs glucose tolerance in lean mice |
abstract |
Objective: Carbonyl reductase 1 (Cbr1), a recently discovered contributor to tissue glucocorticoid metabolism converting corticosterone to 20β-dihydrocorticosterone (20β-DHB), is upregulated in adipose tissue of obese humans and mice and may contribute to cardiometabolic complications of obesity. This study tested the hypothesis that Cbr1-mediated glucocorticoid metabolism influences glucocorticoid and mineralocorticoid receptor activation in adipose tissue and impacts glucose homeostasis in lean and obese states. Methods: The actions of 20β-DHB on corticosteroid receptors in adipose tissue were investigated first using a combination of in silico, in vitro, and transcriptomic techniques and then in vivo administration in combination with receptor antagonists. Mice lacking one Cbr1 allele and mice overexpressing Cbr1 in their adipose tissue underwent metabolic phenotyping before and after induction of obesity with high-fat feeding. Results: 20β-DHB activated both the glucocorticoid and mineralocorticoid receptor in adipose tissue and systemic administration to wild-type mice induced glucose intolerance, an effect that was ameliorated by both glucocorticoid and mineralocorticoid receptor antagonism. Cbr1 haploinsufficient lean male mice had lower fasting glucose and improved glucose tolerance compared with littermate controls, a difference that was abolished by administration of 20β-DHB and absent in female mice with higher baseline adipose 20β-DHB concentrations than male mice. Conversely, overexpression of Cbr1 in adipose tissue resulted in worsened glucose tolerance and higher fasting glucose in lean male and female mice. However, neither Cbr1 haploinsfficiency nor adipose overexpression affected glucose dyshomeostasis induced by high-fat feeding. Conclusions: Carbonyl reductase 1 is a novel regulator of glucocorticoid and mineralocorticoid receptor activation in adipose tissue that influences glucose homeostasis in lean mice. |
abstractGer |
Objective: Carbonyl reductase 1 (Cbr1), a recently discovered contributor to tissue glucocorticoid metabolism converting corticosterone to 20β-dihydrocorticosterone (20β-DHB), is upregulated in adipose tissue of obese humans and mice and may contribute to cardiometabolic complications of obesity. This study tested the hypothesis that Cbr1-mediated glucocorticoid metabolism influences glucocorticoid and mineralocorticoid receptor activation in adipose tissue and impacts glucose homeostasis in lean and obese states. Methods: The actions of 20β-DHB on corticosteroid receptors in adipose tissue were investigated first using a combination of in silico, in vitro, and transcriptomic techniques and then in vivo administration in combination with receptor antagonists. Mice lacking one Cbr1 allele and mice overexpressing Cbr1 in their adipose tissue underwent metabolic phenotyping before and after induction of obesity with high-fat feeding. Results: 20β-DHB activated both the glucocorticoid and mineralocorticoid receptor in adipose tissue and systemic administration to wild-type mice induced glucose intolerance, an effect that was ameliorated by both glucocorticoid and mineralocorticoid receptor antagonism. Cbr1 haploinsufficient lean male mice had lower fasting glucose and improved glucose tolerance compared with littermate controls, a difference that was abolished by administration of 20β-DHB and absent in female mice with higher baseline adipose 20β-DHB concentrations than male mice. Conversely, overexpression of Cbr1 in adipose tissue resulted in worsened glucose tolerance and higher fasting glucose in lean male and female mice. However, neither Cbr1 haploinsfficiency nor adipose overexpression affected glucose dyshomeostasis induced by high-fat feeding. Conclusions: Carbonyl reductase 1 is a novel regulator of glucocorticoid and mineralocorticoid receptor activation in adipose tissue that influences glucose homeostasis in lean mice. |
abstract_unstemmed |
Objective: Carbonyl reductase 1 (Cbr1), a recently discovered contributor to tissue glucocorticoid metabolism converting corticosterone to 20β-dihydrocorticosterone (20β-DHB), is upregulated in adipose tissue of obese humans and mice and may contribute to cardiometabolic complications of obesity. This study tested the hypothesis that Cbr1-mediated glucocorticoid metabolism influences glucocorticoid and mineralocorticoid receptor activation in adipose tissue and impacts glucose homeostasis in lean and obese states. Methods: The actions of 20β-DHB on corticosteroid receptors in adipose tissue were investigated first using a combination of in silico, in vitro, and transcriptomic techniques and then in vivo administration in combination with receptor antagonists. Mice lacking one Cbr1 allele and mice overexpressing Cbr1 in their adipose tissue underwent metabolic phenotyping before and after induction of obesity with high-fat feeding. Results: 20β-DHB activated both the glucocorticoid and mineralocorticoid receptor in adipose tissue and systemic administration to wild-type mice induced glucose intolerance, an effect that was ameliorated by both glucocorticoid and mineralocorticoid receptor antagonism. Cbr1 haploinsufficient lean male mice had lower fasting glucose and improved glucose tolerance compared with littermate controls, a difference that was abolished by administration of 20β-DHB and absent in female mice with higher baseline adipose 20β-DHB concentrations than male mice. Conversely, overexpression of Cbr1 in adipose tissue resulted in worsened glucose tolerance and higher fasting glucose in lean male and female mice. However, neither Cbr1 haploinsfficiency nor adipose overexpression affected glucose dyshomeostasis induced by high-fat feeding. Conclusions: Carbonyl reductase 1 is a novel regulator of glucocorticoid and mineralocorticoid receptor activation in adipose tissue that influences glucose homeostasis in lean mice. |
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title_short |
Carbonyl reductase 1 amplifies glucocorticoid action in adipose tissue and impairs glucose tolerance in lean mice |
url |
https://doi.org/10.1016/j.molmet.2021.101225 https://doaj.org/article/a6432528238548eaaf19f70db5178bdf http://www.sciencedirect.com/science/article/pii/S2212877821000703 https://doaj.org/toc/2212-8778 |
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Elisa Villalobos Mark Nixon Allende Miguelez-Crespo Lee Murphy Angie Fawkes Audrey Coutts Matthew G.F. Sharp Martha V. Koerner Emma Allan Onno C. Meijer Renè Houtman Alex Odermatt Katharina R. Beck Scott G. Denham Patricia Lee Natalie Z.M. Homer Brian R. Walker Ruth A. Morgan |
author2Str |
Elisa Villalobos Mark Nixon Allende Miguelez-Crespo Lee Murphy Angie Fawkes Audrey Coutts Matthew G.F. Sharp Martha V. Koerner Emma Allan Onno C. Meijer Renè Houtman Alex Odermatt Katharina R. Beck Scott G. Denham Patricia Lee Natalie Z.M. Homer Brian R. Walker Ruth A. Morgan |
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10.1016/j.molmet.2021.101225 |
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up_date |
2024-07-03T19:45:07.223Z |
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