Impact of caudal hindbrain glycogen metabolism on A2 noradrenergic neuron AMPK activation and ventromedial hypothalamic nucleus norepinephrine activity and glucoregulatory neurotransmitter marker protein expression.
5’-AMP-activated protein kinase
DAB
L-lactate
Neuronal nitric oxide synthase
Norepinephrine
Ventromedial hypothalamic nucleus
Journal
Neuropeptides
ISSN: 1532-2785
Titre abrégé: Neuropeptides
Pays: Netherlands
ID NLM: 8103156
Informations de publication
Date de publication:
Aug 2020
Aug 2020
Historique:
received:
05
04
2020
revised:
11
05
2020
accepted:
12
05
2020
pubmed:
27
5
2020
medline:
2
6
2021
entrez:
27
5
2020
Statut:
ppublish
Résumé
The brain glycogen reserve is a source of oxidizable substrate fuel. Lactoprivic-sensitive hindbrain A2 noradrenergic neurons provide crucial metabolic-sensory input to downstream hypothalamic glucose-regulatory structures. Current research examined whether hindbrain glycogen fuel supply impacts A2 energy stability and governance of ventromedial hypothalamic nucleus (VMN) metabolic transmitter signaling. Male rats were injected into the caudal fourth ventricle (CV4) with the glycogen phosphorylase inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) prior to continuous intra-CV4 infusion of L-lactate or vehicle. Lactate reversed DAB suppression of A2 neuron AMPK protein and up-regulated phosphoAMPK profiles. A2 dopamine-β-hydroxylase expression was refractory to DAB, but elevated by DAB/lactate. Lactate normalized A2 estrogen receptor-alpha and GPER proteins and up-regulated estrogen receptor-beta levels in DAB-treated rats. VMN norepinephrine content was decreased by DAB, but partially restored by lactate. DAB caused lactate-reversible or -irreversible augmentation of VMN glycogen phosphorylase-brain (GPbb) and -muscle type (GPmm) variant profiles, and correspondingly up- or down-regulated VMN protein markers of glucose-stimulatory nitrergic and glucose-inhibitory γ-aminobutyric acid transmission. DAB did not alter plasma glucose, but suppressed or elevated circulating glucagon and corticosterone in that order. Results show that diminished hindbrain glycogen breakdown is communicated to the VMN, in part by NE signaling, to up-regulate VMN glycogen breakdown and trigger neurochemical signaling of energy imbalance in that site. DAB effects on GPmm, VMN glycogen content, and counter-regulatory hormone secretion were unabated by lactate infusion, suggesting that aside from substrate fuel provision rate, additional indicators of glycogen metabolism such as turnover rate may be monitored in the hindbrain.
Identifiants
pubmed: 32451071
pii: S0143-4179(20)30068-8
doi: 10.1016/j.npep.2020.102055
pmc: PMC7354902
mid: NIHMS1597302
pii:
doi:
Substances chimiques
Glycogen
9005-79-2
AMP-Activated Protein Kinases
EC 2.7.11.31
Norepinephrine
X4W3ENH1CV
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
102055Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK109382
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest None.
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