RT Journal Article
T1 SF1-specific deletion of the energy sensor AMPKγ2 induces obesity
A1 Freire-Agulleiro, Óscar
A1 Estévez Salguero, Ánxela
A1 Ferreira, Vitor
A1 González García, Ismael
A1 Nogueiras Pozo, Rubén
A1 Tena Sempere, Manuel
A1 Diéguez González, Carlos
A1 López Pérez, Miguel A.
K1 AMPK
K1 BAT
K1 Hypothalamus
K1 Obesity
K1 SF1
K1 Thermogenesis
AB ObjectiveAMP-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.MethodsTo 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.ResultsOur 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.ConclusionsOverall, these results highlight the distinct roles of AMPK subunits within the hypothalamus.
PB Elsevier
YR 2025
FD 2025
LK https://hdl.handle.net/10347/42487
UL https://hdl.handle.net/10347/42487
LA eng
NO Molecular Metabolism Volume 92, February 2025, 102091
NO The research leading to these results has received funding from the Xunta de Galicia (IGG and RN: ED431C 2024/10; IGG: ED431F 2024/14; OFA: predoctoral fellowship ED481A-2019026); Ministerio de Ciencia e Innovación co-funded by the FEDER Program of EU (IGG: PID2022-141115NA-I00; RN: RTI2018-099413-B-I00 and RED2018-102379-T; MT-S: PID2020-118660GB-I00; CD: PID2020-116628GB-I00; ML: PID2021-128145NB-I00 and PDC2022-133958-I00); DZD (CGC), the German Research Foundation DFG under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (CGC: EXC 2145 SyNergy–ID 390857198), and Helmholtz Association-Initiative and Networking Fund (CGC); European Research Council (RN: ERC Synergy Grant-2019-WATCH- 810331); 'la Caixa' Foundation (ID 100010434), (ML: LCF/PR/HR19/52160022 and LCF/PR/HR20/52400013); Fundacion Araucaria (ML: PRYGN234908LOPE). IGG is supported by Ramón y Cajal Contract (RYC2021-031225-I) from the Ministerio de Ciencia e Innovación of Spain. CiMUS was supported by the Xunta de Galicia (2020–2023, ED431G/05). CIBER de Fisiopatología de la Obesidad y Nutrición is an initiative of ISCIII. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
DS Minerva
RD 22 abr 2026