Combined loss of GLP-1R and Y2R does not alter progression of high-fat diet-induced obesity or response to RYGB surgery in mice.
Animals
Bariatric Surgery
Blood Glucose
Body Weight
Diet, High-Fat
/ adverse effects
Energy Metabolism
Gastric Bypass
Gene Expression Regulation
Glucagon-Like Peptide-1 Receptor
/ genetics
Insulin
Insulin Resistance
Male
Metabolic Diseases
/ genetics
Mice
Mice, Inbred C57BL
Mice, Knockout
Obesity
/ genetics
Peptide YY
Receptors, G-Protein-Coupled
/ genetics
Transcriptome
Bariatric surgery
Diabetes
GLP-1
Glucose tolerance
Insulin tolerance
PYY
Journal
Molecular metabolism
ISSN: 2212-8778
Titre abrégé: Mol Metab
Pays: Germany
ID NLM: 101605730
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
13
03
2019
revised:
30
04
2019
accepted:
04
05
2019
pubmed:
28
5
2019
medline:
21
4
2020
entrez:
26
5
2019
Statut:
ppublish
Résumé
Understanding the mechanisms underlying the remarkable beneficial effects of gastric bypass surgery is important for the development of non-surgical therapies or less invasive surgeries in the fight against obesity and metabolic disease. Although the intestinal L-cell hormones glucagon-like peptide-1 (GLP-1) and peptide tyrosine-tyrosine (PYY) have attracted the most attention, direct tests in humans and rodents with pharmacological blockade or genetic deletion of either the GLP1-receptor (GLP1R) or the Y2-receptor (Y2R) were unable to confirm their critical roles in the beneficial effects gastric bypass surgery on body weight and glucose homeostasis. However, new awareness of the power of combinatorial therapies in the treatment of metabolic disease would suggest that combined blockade of more than one signaling pathway may be necessary to reverse the beneficial effects of bariatric surgery. The metabolic effects of high-fat diet and the ability of Roux-en-Y gastric bypass surgery to lower food intake and body weight, as well as improve glucose handling, was tested in GLP1R and Y2R-double knockout (GLP1RKO/Y2RKO) and C57BL6J wildtype (WT) mice. GLP1RKO/Y2RKO and WT mice responded similarly for up to 20 weeks on high-fat diet and 16 weeks after RYGB. There were no significant differences in loss of body and liver weight, fat mass, reduced food intake, relative increase in energy expenditure, improved fasting insulin, glucose tolerance, and insulin tolerance between WT and GLP1RKO/Y2RKO mice after RYGB. Combined loss of GLP1R and Y2R-signaling was not able to negate or attenuate the beneficial effects of RYGB on body weight and glucose homeostasis in mice, suggesting that a larger number of signaling pathways is involved or that the critical pathway has not yet been identified.
Identifiants
pubmed: 31126840
pii: S2212-8778(19)30233-9
doi: 10.1016/j.molmet.2019.05.004
pmc: PMC6600699
pii:
doi:
Substances chimiques
Blood Glucose
0
Glp1r protein, mouse
0
Glucagon-Like Peptide-1 Receptor
0
Insulin
0
Receptors, G-Protein-Coupled
0
Peptide YY
106388-42-5
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
64-72Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK047348
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK105032
Pays : United States
Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier GmbH.. All rights reserved.
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