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Freire-Agulleiro, Ó.* ; Estévez-Salguero, Á.* ; Ferreira, V.* ; Holleman, C.L. ; García-Currás, J.* ; González-García, I.* ; Nogueiras, R.* ; Tena-Sempere, M.* ; García-Cáceres, C. ; Diéguez, C.* ; López, M.*

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

Mol. Metab. 92:102091 (2024)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Ampk ; Bat ; Sf1 ; Hypothalamus ; Obesity ; Thermogenesis; Activated Protein-kinase; Adipose-tissue Thermogenesis; Hypothalamic Ampk; Ventromedial Hypothalamus; Thyroid-hormones; Nutrient; Neurons; Glucose; Homeostasis; Expression
Sprache englisch
Veröffentlichungsjahr 2024
HGF-Berichtsjahr 2024
ISSN (print) / ISBN 2212-8778
e-ISSN 2212-8778
Zeitschrift Molecular Metabolism
Quellenangaben Band: 92, Heft: , Seiten: , Artikelnummer: 102091 Supplement: ,
Verlag Elsevier
Verlagsort Amsterdam
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Obesity (IDO)
POF Topic(s) 30201 - Metabolic Health
90000 - German Center for Diabetes Research
Forschungsfeld(er) Helmholtz Diabetes Center
PSP-Element(e) G-502200-001
G-501900-224
Förderungen Helmholtz Association-Initiative and Networking Fund (CGC)
European Research Council
La Caixa Foundation
Fundacion Araucaria
Ramon y Cajal from the Ministerio de Ciencia e Innovacion of Spain
German Research Foundation DFG under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology
FEDER Program of EU
Xunta de Galicia
Ministerio de Ciencia e Innovacion
DOI 10.1016/j.molmet.2024.102091
WOS ID 001400621200001
Scopus ID 85214577770
PubMed ID 39746605
Erfassungsdatum 2025-01-10
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