Adipocyte Gs but not Gi signaling regulates whole-body glucose homeostasis.
Adipocytes
/ metabolism
Animals
GTP-Binding Protein alpha Subunits, Gi-Go
/ metabolism
GTP-Binding Protein alpha Subunits, Gs
/ metabolism
Glucose
/ metabolism
Homeostasis
Hypoglycemia
/ metabolism
Insulin
/ metabolism
Leptin
/ metabolism
Male
Mice, Inbred C57BL
Receptors, G-Protein-Coupled
/ metabolism
Signal Transduction
Adipose tissue
DREADD
Glucose
Insulin
Leptin
Lipolysis
Journal
Molecular metabolism
ISSN: 2212-8778
Titre abrégé: Mol Metab
Pays: Germany
ID NLM: 101605730
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
14
05
2019
revised:
20
06
2019
accepted:
20
06
2019
pubmed:
8
7
2019
medline:
14
4
2020
entrez:
8
7
2019
Statut:
ppublish
Résumé
The sympathetic nervous system (SNS) is a key regulator of the metabolic and endocrine functions of adipose tissue. Increased SNS outflow promotes fat mobilization, stimulates non-shivering thermogenesis, promotes browning, and inhibits leptin production. Most of these effects are attributed to norepinephrine activation of the Gs-coupled beta adrenergic receptors located on the surface of the adipocytes. Evidence suggests that other adrenergic receptor subtypes, including the Gi-coupled alpha 2 adrenergic receptors might also mediate the SNS effects on adipose tissue. However, the impact of acute stimulation of adipocyte Gs and Gi has never been reported. We harness the power of chemogenetics to develop unique mouse models allowing the specific and spatiotemporal stimulation of adipose tissue Gi and Gs signaling. We evaluated the impact of chemogenetic stimulation of these pathways on glucose homeostasis, lipolysis, leptin production, and gene expression. Stimulation of Gs signaling in adipocytes induced rapid and sustained hypoglycemia. These hypoglycemic effects were secondary to increased insulin release, likely consequent to increased lipolysis. Notably, we also observed differences in gene regulation and ex vivo lipolysis in different adipose depots. In contrast, acute stimulation of Gi signaling in adipose tissue did not affect glucose metabolism or lipolysis, but regulated leptin production. Our data highlight the significance of adipose Gs signaling in regulating systemic glucose homeostasis. We also found previously unappreciated heterogeneity across adipose depots following acute stimulation. Together, these results highlight the complex interactions of GPCR signaling in adipose tissue and demonstrate the usefulness of chemogenetic technology to better understand adipocyte function.
Identifiants
pubmed: 31279640
pii: S2212-8778(19)30391-6
doi: 10.1016/j.molmet.2019.06.019
pmc: PMC6717754
pii:
doi:
Substances chimiques
Insulin
0
Leptin
0
Receptors, G-Protein-Coupled
0
GTP-Binding Protein alpha Subunits, Gi-Go
EC 3.6.5.1
GTP-Binding Protein alpha Subunits, Gs
EC 3.6.5.1
Glucose
IY9XDZ35W2
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
11-21Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR059847
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK092590
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK118725
Pays : United States
Organisme : NIDDK NIH HHS
ID : K01 DK111644
Pays : United States
Organisme : NIDDK NIH HHS
ID : K99 DK120894
Pays : United States
Organisme : CIHR
Pays : Canada
Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier GmbH.. All rights reserved.
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