SF1-specific deletion of the energy sensor AMPKγ2 induces obesity
Year: 2024
Type: article
Abstract: 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.
Source: Molecular Metabolism
Institutions: Universidade de Santiago de Compostela, Center for Research in Molecular Medicine and Chronic Diseases, Helmholtz Munich, German Center for Diabetes Research, Instituto Maimónides de Investigación Biomédica de Córdoba, Hospital Universitario Reina Sofía, University of Córdoba, Ludwig-Maximilians-Universität München
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,870
Funders: Deutsches Krebsforschungszentrum, Fundacion Araucaria, Deutsche Forschungsgemeinschaft, Ministerio de Ciencia e Innovación, Helmholtz Association, Xunta de Galicia, Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición, European Research Council, Instituto de Salud Carlos III, H2020 European Research Council
Awards: G1044294895, G1098384179, G1241847824, G140035165, G1496055848, G1650125035, G1690154432, G1789099517, G2085528529, G2290189609, G238895617, G289143459, G2951169516, G33163370, G3787221488, G3876637791, EXC 2145: Munich Cluster for Systems Neurology (SyNergy), G4008533023, G412886171, G4462967385, G4944594896, G5122703620, G526084217, G5280119642, G5555642676, G559812186, G5683724937, G5805502524, G5879698894, G6815693670, G6837718744, G7036029898, G7061792836, G7915813472, G8079636847, G8347645112, G8612360239, G8727666142, G891209587, G8920660035
OpenAlex ID: W4405926187