SF1-specific deletion of the energy sensor AMPKγ2 induces obesity
Objective: AMP-activated protein kinase (AMPK) is a heterotrimer complex consisting of a catalytic α subunit (α1, α2) with a serine/threonine kinase domain, and two regulatory subunits, β (β1, β2) and γ (γ1, γ2, γ3), encoded by different genes. In the hypothalamus, AMPK plays a crucial role in regul...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | Molecular Metabolism |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877824002229 |
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| author | Óscar Freire-Agulleiro Ánxela Estévez-Salguero Vitor Ferreira Cassie Lynn Holleman Julia García-Currás Ismael González-García Rubén Nogueiras Manuel Tena-Sempere Cristina García-Cáceres Carlos Diéguez Miguel López |
| author_facet | Óscar Freire-Agulleiro Ánxela Estévez-Salguero Vitor Ferreira Cassie Lynn Holleman Julia García-Currás Ismael González-García Rubén Nogueiras Manuel Tena-Sempere Cristina García-Cáceres Carlos Diéguez Miguel López |
| author_sort | Óscar Freire-Agulleiro |
| collection | DOAJ |
| description | Objective: AMP-activated protein kinase (AMPK) is a heterotrimer complex consisting of a catalytic α subunit (α1, α2) with a serine/threonine kinase domain, and two regulatory subunits, β (β1, β2) and γ (γ1, γ2, γ3), encoded by different genes. In the hypothalamus, AMPK plays a crucial role in regulating energy balance, including feeding, energy expenditure, peripheral glucose and lipid metabolism. However, most research on hypothalamic AMPK has concentrated on the catalytic subunits AMPKα1 and AMPKα2, with little focus on the regulatory subunits. Methods: To fill this gap of knowledge, we investigated the effects of selectively deleting the regulatory isoform AMPKγ2, which is a primary “energy sensor”, in steroidogenic factor 1 (SF1) neurons of the ventromedial hypothalamic nucleus (VMH). Complete metabolic phenotyping and molecular analyses in brown adipose tissue (BAT), white adipose tissue (WAT) and liver were carried out. Results: Our findings reveal that, in contrast to the obesity-protective effect of the genetic deletion of AMPKα subunits, the loss of AMPKγ2 in SF1 neurons leads to a sex-independent and feeding-independent obesity-prone phenotype due to decreased thermogenesis in brown adipose tissue (BAT) and reduced browning of WAT, resulting in lower energy expenditure. Additionally, SF1-Cre AMPKγ2 mice exhibit hepatic lipid accumulation, but surprisingly maintain normal glucose homeostasis. Conclusions: Overall, these results highlight the distinct roles of AMPK subunits within the hypothalamus. |
| format | Article |
| id | doaj-art-9f0c9c728d3b46e5aea64f03df12a575 |
| institution | Kabale University |
| issn | 2212-8778 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj-art-9f0c9c728d3b46e5aea64f03df12a5752025-02-01T04:11:58ZengElsevierMolecular Metabolism2212-87782025-02-0192102091SF1-specific deletion of the energy sensor AMPKγ2 induces obesityÓscar Freire-Agulleiro0Ánxela Estévez-Salguero1Vitor Ferreira2Cassie Lynn Holleman3Julia García-Currás4Ismael González-García5Rubén Nogueiras6Manuel Tena-Sempere7Cristina García-Cáceres8Carlos Diéguez9Miguel López10Department of Physiology, CiMUS, University of Santiago de Compostela, Santiago de Compostela, 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Santiago de Compostela, 15706, SpainDepartment of Physiology, CiMUS, University of Santiago de Compostela, Santiago de Compostela, 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Santiago de Compostela, 15706, SpainDepartment of Physiology, CiMUS, University of Santiago de Compostela, Santiago de Compostela, 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Santiago de Compostela, 15706, SpainInstitute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, 85764, Neuherberg, Germany; German Center for Diabetes Research (DZD), 85764, Neuherberg, GermanyBiostatech Advice, Training and Innovation in Biostatistics, S.L, Ames, 15895, SpainDepartment of Physiology, CiMUS, University of Santiago de Compostela, Santiago de Compostela, 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Santiago de Compostela, 15706, SpainDepartment of Physiology, CiMUS, University of Santiago de Compostela, Santiago de Compostela, 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Santiago de Compostela, 15706, SpainCIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Santiago de Compostela, 15706, Spain; Department of Cell Biology, Physiology and Immunology, University of Córdoba, Instituto Maimónides de Investigación Biomédica (IMIBIC)/Hospital Universitario Reina Sofía, Córdoba, 14004, SpainInstitute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, 85764, Neuherberg, Germany; German Center for Diabetes Research (DZD), 85764, Neuherberg, Germany; Medizinische Klinik und Poliklinik IV, Klinikum der Universität, Ludwig-Maximilians-Universität München, 80336, Munich, GermanyDepartment of Physiology, CiMUS, University of Santiago de Compostela, Santiago de Compostela, 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Santiago de Compostela, 15706, SpainDepartment of Physiology, CiMUS, University of Santiago de Compostela, Santiago de Compostela, 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Santiago de Compostela, 15706, Spain; Corresponding author. Department of Physiology, CiMUS, University of Santiago de Compostela, Santiago de Compostela, 15782, Spain.Objective: AMP-activated protein kinase (AMPK) is a heterotrimer complex consisting of a catalytic α subunit (α1, α2) with a serine/threonine kinase domain, and two regulatory subunits, β (β1, β2) and γ (γ1, γ2, γ3), encoded by different genes. In the hypothalamus, AMPK plays a crucial role in regulating energy balance, including feeding, energy expenditure, peripheral glucose and lipid metabolism. However, most research on hypothalamic AMPK has concentrated on the catalytic subunits AMPKα1 and AMPKα2, with little focus on the regulatory subunits. Methods: To fill this gap of knowledge, we investigated the effects of selectively deleting the regulatory isoform AMPKγ2, which is a primary “energy sensor”, in steroidogenic factor 1 (SF1) neurons of the ventromedial hypothalamic nucleus (VMH). Complete metabolic phenotyping and molecular analyses in brown adipose tissue (BAT), white adipose tissue (WAT) and liver were carried out. Results: Our findings reveal that, in contrast to the obesity-protective effect of the genetic deletion of AMPKα subunits, the loss of AMPKγ2 in SF1 neurons leads to a sex-independent and feeding-independent obesity-prone phenotype due to decreased thermogenesis in brown adipose tissue (BAT) and reduced browning of WAT, resulting in lower energy expenditure. Additionally, SF1-Cre AMPKγ2 mice exhibit hepatic lipid accumulation, but surprisingly maintain normal glucose homeostasis. Conclusions: Overall, these results highlight the distinct roles of AMPK subunits within the hypothalamus.http://www.sciencedirect.com/science/article/pii/S2212877824002229AMPKBATHypothalamusObesitySF1Thermogenesis |
| spellingShingle | Óscar Freire-Agulleiro Ánxela Estévez-Salguero Vitor Ferreira Cassie Lynn Holleman Julia García-Currás Ismael González-García Rubén Nogueiras Manuel Tena-Sempere Cristina García-Cáceres Carlos Diéguez Miguel López SF1-specific deletion of the energy sensor AMPKγ2 induces obesity Molecular Metabolism AMPK BAT Hypothalamus Obesity SF1 Thermogenesis |
| title | SF1-specific deletion of the energy sensor AMPKγ2 induces obesity |
| title_full | SF1-specific deletion of the energy sensor AMPKγ2 induces obesity |
| title_fullStr | SF1-specific deletion of the energy sensor AMPKγ2 induces obesity |
| title_full_unstemmed | SF1-specific deletion of the energy sensor AMPKγ2 induces obesity |
| title_short | SF1-specific deletion of the energy sensor AMPKγ2 induces obesity |
| title_sort | sf1 specific deletion of the energy sensor ampkγ2 induces obesity |
| topic | AMPK BAT Hypothalamus Obesity SF1 Thermogenesis |
| url | http://www.sciencedirect.com/science/article/pii/S2212877824002229 |
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