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The Deubiquitinase OTUB1 Is a Key Regulator of Energy Metabolism

Dysregulated energy metabolism is a major contributor to a multitude of pathologies, including obesity and diabetes. Understanding the regulation of metabolic homeostasis is of utmost importance for the identification of therapeutic targets for the treatment of metabolically driven diseases. We prev...

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Autores principales: Ruiz-Serrano, Amalia, Boyle, Christina N., Monné Rodríguez, Josep M., Günter, Julia, Jucht, Agnieszka E., Pfundstein, Svende, Bapst, Andreas M., Lutz, Thomas A., Wenger, Roland H., Scholz, Carsten C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8836018/
https://www.ncbi.nlm.nih.gov/pubmed/35163456
http://dx.doi.org/10.3390/ijms23031536
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author Ruiz-Serrano, Amalia
Boyle, Christina N.
Monné Rodríguez, Josep M.
Günter, Julia
Jucht, Agnieszka E.
Pfundstein, Svende
Bapst, Andreas M.
Lutz, Thomas A.
Wenger, Roland H.
Scholz, Carsten C.
author_facet Ruiz-Serrano, Amalia
Boyle, Christina N.
Monné Rodríguez, Josep M.
Günter, Julia
Jucht, Agnieszka E.
Pfundstein, Svende
Bapst, Andreas M.
Lutz, Thomas A.
Wenger, Roland H.
Scholz, Carsten C.
author_sort Ruiz-Serrano, Amalia
collection PubMed
description Dysregulated energy metabolism is a major contributor to a multitude of pathologies, including obesity and diabetes. Understanding the regulation of metabolic homeostasis is of utmost importance for the identification of therapeutic targets for the treatment of metabolically driven diseases. We previously identified the deubiquitinase OTUB1 as substrate for the cellular oxygen sensor factor-inhibiting HIF (FIH) with regulatory effects on cellular energy metabolism, but the physiological relevance of OTUB1 is unclear. Here, we report that the induced global deletion of OTUB1 in adult mice (Otub1 iKO) elevated energy expenditure, reduced age-dependent body weight gain, facilitated blood glucose clearance and lowered basal plasma insulin levels. The respiratory exchange ratio was maintained, indicating an unaltered nutrient oxidation. In addition, Otub1 deletion in cells enhanced AKT activity, leading to a larger cell size, higher ATP levels and reduced AMPK phosphorylation. AKT is an integral part of insulin-mediated signaling and Otub1 iKO mice presented with increased AKT phosphorylation following acute insulin administration combined with insulin hypersensitivity. We conclude that OTUB1 is an important regulator of metabolic homeostasis.
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spelling pubmed-88360182022-02-12 The Deubiquitinase OTUB1 Is a Key Regulator of Energy Metabolism Ruiz-Serrano, Amalia Boyle, Christina N. Monné Rodríguez, Josep M. Günter, Julia Jucht, Agnieszka E. Pfundstein, Svende Bapst, Andreas M. Lutz, Thomas A. Wenger, Roland H. Scholz, Carsten C. Int J Mol Sci Article Dysregulated energy metabolism is a major contributor to a multitude of pathologies, including obesity and diabetes. Understanding the regulation of metabolic homeostasis is of utmost importance for the identification of therapeutic targets for the treatment of metabolically driven diseases. We previously identified the deubiquitinase OTUB1 as substrate for the cellular oxygen sensor factor-inhibiting HIF (FIH) with regulatory effects on cellular energy metabolism, but the physiological relevance of OTUB1 is unclear. Here, we report that the induced global deletion of OTUB1 in adult mice (Otub1 iKO) elevated energy expenditure, reduced age-dependent body weight gain, facilitated blood glucose clearance and lowered basal plasma insulin levels. The respiratory exchange ratio was maintained, indicating an unaltered nutrient oxidation. In addition, Otub1 deletion in cells enhanced AKT activity, leading to a larger cell size, higher ATP levels and reduced AMPK phosphorylation. AKT is an integral part of insulin-mediated signaling and Otub1 iKO mice presented with increased AKT phosphorylation following acute insulin administration combined with insulin hypersensitivity. We conclude that OTUB1 is an important regulator of metabolic homeostasis. MDPI 2022-01-28 /pmc/articles/PMC8836018/ /pubmed/35163456 http://dx.doi.org/10.3390/ijms23031536 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ruiz-Serrano, Amalia
Boyle, Christina N.
Monné Rodríguez, Josep M.
Günter, Julia
Jucht, Agnieszka E.
Pfundstein, Svende
Bapst, Andreas M.
Lutz, Thomas A.
Wenger, Roland H.
Scholz, Carsten C.
The Deubiquitinase OTUB1 Is a Key Regulator of Energy Metabolism
title The Deubiquitinase OTUB1 Is a Key Regulator of Energy Metabolism
title_full The Deubiquitinase OTUB1 Is a Key Regulator of Energy Metabolism
title_fullStr The Deubiquitinase OTUB1 Is a Key Regulator of Energy Metabolism
title_full_unstemmed The Deubiquitinase OTUB1 Is a Key Regulator of Energy Metabolism
title_short The Deubiquitinase OTUB1 Is a Key Regulator of Energy Metabolism
title_sort deubiquitinase otub1 is a key regulator of energy metabolism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8836018/
https://www.ncbi.nlm.nih.gov/pubmed/35163456
http://dx.doi.org/10.3390/ijms23031536
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