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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)
Publ. Version/Full Text DOI PMC
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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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Publication type Article: Journal article
Document type Scientific Article
Keywords Ampk ; Bat ; Sf1 ; Hypothalamus ; Obesity ; Thermogenesis; Activated Protein-kinase; Adipose-tissue Thermogenesis; Hypothalamic Ampk; Ventromedial Hypothalamus; Thyroid-hormones; Nutrient; Neurons; Glucose; Homeostasis; Expression
Language english
Publication Year 2024
HGF-reported in Year 2024
ISSN (print) / ISBN 2212-8778
e-ISSN 2212-8778
Journal Molecular Metabolism
Quellenangaben Volume: 92, Issue: , Pages: , Article Number: 102091 Supplement: ,
Publisher Elsevier
Publishing Place Amsterdam
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Obesity (IDO)
POF-Topic(s) 30201 - Metabolic Health
90000 - German Center for Diabetes Research
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-502200-001
G-501900-224
Grants 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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