Blunted Vagal Cocaine- and Amphetamine-Regulated Transcript Promotes Hyperphagia and Weight Gain.

Animals Humans Hyperphagia / genetics Male Nerve Tissue Proteins / metabolism Rats Vagus Nerve / drug effects Weight Gain / genetics
NTS cholecystokinin diet-induced obesity food intake ingestion neuropeptide nodose ganglia nucleus tractus solitarii vagal afferent neurons vagus nerve

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
11 02 2020
Historique:
received: 20 08 2019
revised: 06 12 2019
accepted: 15 01 2020
entrez: 13 2 2020
pubmed: 13 2 2020
medline: 9 3 2021
Statut: ppublish

Résumé

The vagus nerve conveys gastrointestinal cues to the brain to control eating behavior. In obesity, vagally mediated gut-brain signaling is disrupted. Here, we show that the cocaine- and amphetamine-regulated transcript (CART) is a neuropeptide synthesized proportional to the food consumed in vagal afferent neurons (VANs) of chow-fed rats. CART injection into the nucleus tractus solitarii (NTS), the site of vagal afferent central termination, reduces food intake. Conversely, blocking endogenous CART action in the NTS increases food intake in chow-fed rats, and this requires intact VANs. Viral-mediated Cartpt knockdown in VANs increases weight gain and daily food intake via larger meals and faster ingestion rate. In obese rats fed a high-fat, high-sugar diet, meal-induced CART synthesis in VANs is blunted and CART antibody fails to increase food intake. However, CART injection into the NTS retains its anorexigenic effect in obese rats. Restoring disrupted VAN CART signaling in obesity could be a promising therapeutic approach.

Identifiants

DOI: 10.1016/j.celrep.2020.01.045 PMID: 32049029 PMC: PMC7063787
pubmed: 32049029
pii: S2211-1247(20)30069-3
doi: 10.1016/j.celrep.2020.01.045
pmc: PMC7063787
mid: NIHMS1560135
pii:
doi:

Substances chimiques

Nerve Tissue Proteins 0
cocaine- and amphetamine-regulated transcript protein 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2028-2039.e4

Subventions

Organisme : NIDDK NIH HHS
ID : K99 DK094871
Pays : United States
Organisme : NIDDK NIH HHS
ID : R00 DK094871
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK116004
Pays : United States

Informations de copyright

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Interests The authors declare no competing interests.

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Auteurs

Shin J Lee (SJ)

Physiology and Behavior Laboratory, ETH Zurich, Schwerzenbach, Switzerland.

Jean-Philippe Krieger (JP)

Physiology and Behavior Laboratory, ETH Zurich, Schwerzenbach, Switzerland; Department of Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.

Macarena Vergara (M)

Department of Pharmacodynamics, Center for Integrative Cardiovascular and Metabolic Disease, University of Florida, Gainesville, FL, USA.

Danielle Quinn (D)

The John B. Pierce Laboratory, New Haven, CT, USA.

Molly McDougle (M)

Department of Pharmacodynamics, Center for Integrative Cardiovascular and Metabolic Disease, University of Florida, Gainesville, FL, USA; The John B. Pierce Laboratory, New Haven, CT, USA.

Alan de Araujo (A)

Department of Pharmacodynamics, Center for Integrative Cardiovascular and Metabolic Disease, University of Florida, Gainesville, FL, USA; The John B. Pierce Laboratory, New Haven, CT, USA; Yale University, New Haven, CT, USA.

Rebecca Darling (R)

Anatomy, Physiology and Cell Biology Department School of Veterinary Medicine, University of California Davis, Davis, CA, USA.

Benjamin Zollinger (B)

The John B. Pierce Laboratory, New Haven, CT, USA; Yale University, New Haven, CT, USA.

Seth Anderson (S)

The John B. Pierce Laboratory, New Haven, CT, USA; Yale University, New Haven, CT, USA.

Annabeth Pan (A)

The John B. Pierce Laboratory, New Haven, CT, USA; Yale University, New Haven, CT, USA.

Emilie J Simonnet (EJ)

Anatomy, Physiology and Cell Biology Department School of Veterinary Medicine, University of California Davis, Davis, CA, USA.

Angelica Pignalosa (A)

Physiology and Behavior Laboratory, ETH Zurich, Schwerzenbach, Switzerland.

Myrtha Arnold (M)

Physiology and Behavior Laboratory, ETH Zurich, Schwerzenbach, Switzerland.

Arashdeep Singh (A)

Department of Pharmacodynamics, Center for Integrative Cardiovascular and Metabolic Disease, University of Florida, Gainesville, FL, USA.

Wolfgang Langhans (W)

Physiology and Behavior Laboratory, ETH Zurich, Schwerzenbach, Switzerland.

Helen E Raybould (HE)

Anatomy, Physiology and Cell Biology Department School of Veterinary Medicine, University of California Davis, Davis, CA, USA.

Guillaume de Lartigue (G)

Department of Pharmacodynamics, Center for Integrative Cardiovascular and Metabolic Disease, University of Florida, Gainesville, FL, USA; The John B. Pierce Laboratory, New Haven, CT, USA; Yale University, New Haven, CT, USA. Electronic address: gdelartigue@ufl.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Blunted Vagal Cocaine- and...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Blunted Vagal Cocaine- and...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Signes et symptômes digestifs › Hyperphagie › Blunted Vagal Cocaine- and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Blunted Vagal Cocaine- and...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › Blunted Vagal Cocaine- and...
questionsmedicales.fr › Système nerveux › Système nerveux périphérique › Nerfs périphériques › Nerfs crâniens › Nerf vague › Blunted Vagal Cocaine- and...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Mensurations corporelles › Poids › Modifications du poids corporel › Prise de poids › Blunted Vagal Cocaine- and...