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Häusl, A.S.* ; Bajaj, T.* ; Brix, L.M.* ; Pöhlmann, M.L.* ; Hafner, K.* ; de Angelis, M. ; Nagler, J. ; Dethloff, F.* ; Balsevich, G.* ; Schramm, K.-W. ; Giavalisco, P.* ; Chen, A.* ; Schmidt, M.V.* ; Gassen, N.C.*

Mediobasal hypothalamic FKBP51 acts as a molecular switch linking autophagy to whole-body metabolism.

Sci. Adv. 8:eabi4797 (2022)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The mediobasal hypothalamus (MBH) is the central region in the physiological response to metabolic stress. The FK506-binding protein 51 (FKBP51) is a major modulator of the stress response and has recently emerged as a scaffolder regulating metabolic and autophagy pathways. However, the detailed protein-protein interactions linking FKBP51 to autophagy upon metabolic challenges remain elusive. We performed mass spectrometry-based metabolomics of FKBP51 knockout (KO) cells revealing an increased amino acid and polyamine metabolism. We identified FKBP51 as a central nexus for the recruitment of the LKB1/AMPK complex to WIPI4 and TSC2 to WIPI3, thereby regulating the balance between autophagy and mTOR signaling in response to metabolic challenges. Furthermore, we demonstrated that MBH FKBP51 deletion strongly induces obesity, while its overexpression protects against high-fat diet (HFD)-induced obesity. Our study provides an important novel regulatory function of MBH FKBP51 within the stress-adapted autophagy response to metabolic challenges.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Diet-induced Obesity; Chain Amino-acids; Food-intake; Signaling Pathway; Mass-spectrometry; Adipose-tissue; Ampk; Expression; Stress; Mtor
Sprache englisch
Veröffentlichungsjahr 2022
HGF-Berichtsjahr 2022
ISSN (print) / ISBN 2375-2548
e-ISSN 2375-2548
Zeitschrift Science Advances
Quellenangaben Band: 8, Heft: 10, Seiten: , Artikelnummer: eabi4797 Supplement: ,
Verlag American Association for the Advancement of Science (AAAS)
Verlagsort Washington, DC [u.a.]
Begutachtungsstatus Peer reviewed
Institut(e) PPM-MEX-Molecular EXposomics (MEX)
POF Topic(s) 30202 - Environmental Health
Forschungsfeld(er) Environmental Sciences
PSP-Element(e) G-509100-001
Förderungen "Kids2Health"grant of the Federal Ministry of Education and Research
"GUTMOM" grant of the Federal Ministry of Education and Research
BioM M4 award "PROCERA" of the Bavarian State Ministry
Federal Ministry of Education and Research
DOI 10.1126/sciadv.abi4797
WOS ID WOS:000766438000018
Scopus ID 85126079185
PubMed ID 35263141
Erfassungsdatum 2022-05-02
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