PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Gruber, T. ; Contreras, R. ; Sánchez Quant, E.S. ; Miok, V. ; Makris, K. ; Le Thuc, O. ; Gonzales García, I. ; Garcia-Clavé, E. ; Althammer, F.* ; Krabichler, Q.* ; DeCamp, L.M.* ; Jones, R.G.* ; Lutter, D. ; Williams, R.H. ; Pfluger, P.T. ; Müller, T.D. ; Woods, S.C.* ; Pospisilik, J.A.* ; Martinez-Jimenez, C.P.* ; Tschöp, M.H. ; Grinevich, V.* ; García-Cáceres, C.

High-calorie diets uncouple hypothalamic oxytocin neurons from a gut-to-brain satiation pathway via κ-opioid signaling.

Cell Rep. 42:113305 (2023)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Oxytocin-expressing paraventricular hypothalamic neurons (PVNOT neurons) integrate afferent signals from the gut, including cholecystokinin (CCK), to adjust whole-body energy homeostasis. However, the molecular underpinnings by which PVNOT neurons orchestrate gut-to-brain feeding control remain unclear. Here, we show that mice undergoing selective ablation of PVNOT neurons fail to reduce food intake in response to CCK and develop hyperphagic obesity on a chow diet. Notably, exposing wild-type mice to a high-fat/high-sugar (HFHS) diet recapitulates this insensitivity toward CCK, which is linked to diet-induced transcriptional and electrophysiological aberrations specifically in PVNOT neurons. Restoring OT pathways in diet-induced obese (DIO) mice via chemogenetics or polypharmacology sufficiently re-establishes CCK's anorexigenic effects. Last, by single-cell profiling, we identify a specialized PVNOT neuronal subpopulation with increased κ-opioid signaling under an HFHS diet, which restrains their CCK-evoked activation. In sum, we document a (patho)mechanism by which PVNOT signaling uncouples a gut-brain satiation pathway under obesogenic conditions.
Impact Factor
Scopus SNIP
Altmetric
8.800
0.000
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Cck ; Cp: Neuroscience ; Nts ; Pvn ; Gut Hormone ; Gut-brain Axis ; Neuropeptide ; Obesity ; Opioids ; Oxytocin ; Paraventricular Hypothalamic Nucleus; High-fat Diet; Paraventricular Nucleus; Food-intake; Noradrenaline Release; Rna-seq; Supraoptic Nucleus; Vagal Afferent; Messenger-rna; Cholecystokinin; Receptor
Sprache englisch
Veröffentlichungsjahr 2023
HGF-Berichtsjahr 2023
ISSN (print) / ISBN 2211-1247
e-ISSN 2211-1247
Zeitschrift Cell Reports
Quellenangaben Band: 42, Heft: 10, Seiten: , Artikelnummer: 113305 Supplement: ,
Verlag Cell Press
Verlagsort 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Obesity (IDO)
Helmholtz Pioneer Campus (HPC)
Institute of Neurogenomics (ING)
POF Topic(s) 90000 - German Center for Diabetes Research
30201 - Metabolic Health
30204 - Cell Programming and Repair
30205 - Bioengineering and Digital Health
Forschungsfeld(er) Helmholtz Diabetes Center
Pioneer Campus
Genetics and Epidemiology
PSP-Element(e) G-501900-224
G-502200-001
G-510005-001
G-501900-221
G-502297-001
G-555100-001
G-502294-001
Förderungen European Union
European 748 Research Council ERC
Helmholtz Pioneer Campus
German Research Foundation (DFG)
Marie Sk1odowska-Curie grant
German Center for Diabetes Research (DZD e.V.)
European Research Council ERC-CoG Trust
Germany-Israel Excellence Program
European Research Council (ERC) (Synergy ERC)
European Research Council (ERC)
Helm-holtz Excellence Network
German Center for Diabetes Research (DZD) twinning grant
DOI 10.1016/j.celrep.2023.113305
WOS ID 001105799000001
Scopus ID 85174456579
PubMed ID 37864798
Erfassungsdatum 2023-11-28
[➜Korrektur melden]