SF1-specific deletion of the energy sensor AMPKγ2 induces obesity.

Autor:	Freire-Agulleiro Ó; Department 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., Estévez-Salguero Á; Department 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., Ferreira V; Department 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., Holleman CL; Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, 85764 Neuherberg, Germany; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany., García-Currás J; Biostatech Advice, Training and Innovation in Biostatistics, S.L Santiago de Compostela, 15782, Spain., González-García I; Department 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., Nogueiras R; Department 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., Tena-Sempere M; CIBER 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, Spain., García-Cáceres C; Institute 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, Germany., Diéguez C; Department 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., López M; Department 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. Electronic address: m.lopez@usc.es.
Jazyk:	angličtina
Zdroj:	Molecular metabolism [Mol Metab] 2024 Dec 31, pp. 102091. Date of Electronic Publication: 2024 Dec 31.
DOI:	10.1016/j.molmet.2024.102091
Abstrakt:	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 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. (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)
Databáze:	MEDLINE
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