The PYY/Y2R-Deficient Mouse Responds Normally to High-Fat Diet and Gastric Bypass Surgery.
body composition
body weight
diabetes
energy expenditure
glucose tolerance
incretin
insulin tolerance
obesity
Journal
Nutrients
ISSN: 2072-6643
Titre abrégé: Nutrients
Pays: Switzerland
ID NLM: 101521595
Informations de publication
Date de publication:
10 Mar 2019
10 Mar 2019
Historique:
received:
10
02
2019
revised:
04
03
2019
accepted:
05
03
2019
entrez:
13
3
2019
pubmed:
13
3
2019
medline:
19
6
2019
Statut:
epublish
Résumé
The gut hormone peptide YY (PYY) secreted from intestinal L-cells has been implicated in the mechanisms of satiation via Y2-receptor (Y2R) signaling in the brain and periphery and is a major candidate for mediating the beneficial effects of bariatric surgery on appetite and body weight. Here we assessed the role of Y2R signaling in the response to low- and high-fat diets and its role in the effects of Roux-en-Y gastric bypass (RYGB) surgery on body weight, body composition, food intake, energy expenditure and glucose handling, in global Y2R-deficient (Y2RKO) and wildtype (WT) mice made obese on high-fat diet. Both male and female Y2RKO mice responded normally to low- and high-fat diet in terms of body weight, body composition, fasting levels of glucose and insulin, as well as glucose and insulin tolerance for up to 30 weeks of age. Contrary to expectations, obese Y2RKO mice also responded similarly to RYGB compared to WT mice for up to 20 weeks after surgery, with initial hypophagia, sustained body weight loss, and significant improvements in fasting insulin, glucose tolerance, insulin resistance (HOMA-IR), and liver weight compared to sham-operated mice. Furthermore, non-surgical Y2RKO mice weight-matched to RYGB showed the same improvements in glycemic control as Y2RKO mice with RYGB that were similar to WT mice. PYY signaling through Y2R is not required for the normal appetite-suppressing and body weight-lowering effects of RYGB in this global knockout mouse model. Potential compensatory adaptations of PYY signaling through other receptor subtypes or other gut satiety hormones such as glucagon-like peptide-1 (GLP-1) remain to be investigated.
Sections du résumé
BACKGROUND/GOALS
OBJECTIVE
The gut hormone peptide YY (PYY) secreted from intestinal L-cells has been implicated in the mechanisms of satiation via Y2-receptor (Y2R) signaling in the brain and periphery and is a major candidate for mediating the beneficial effects of bariatric surgery on appetite and body weight.
METHODS
METHODS
Here we assessed the role of Y2R signaling in the response to low- and high-fat diets and its role in the effects of Roux-en-Y gastric bypass (RYGB) surgery on body weight, body composition, food intake, energy expenditure and glucose handling, in global Y2R-deficient (Y2RKO) and wildtype (WT) mice made obese on high-fat diet.
RESULTS
RESULTS
Both male and female Y2RKO mice responded normally to low- and high-fat diet in terms of body weight, body composition, fasting levels of glucose and insulin, as well as glucose and insulin tolerance for up to 30 weeks of age. Contrary to expectations, obese Y2RKO mice also responded similarly to RYGB compared to WT mice for up to 20 weeks after surgery, with initial hypophagia, sustained body weight loss, and significant improvements in fasting insulin, glucose tolerance, insulin resistance (HOMA-IR), and liver weight compared to sham-operated mice. Furthermore, non-surgical Y2RKO mice weight-matched to RYGB showed the same improvements in glycemic control as Y2RKO mice with RYGB that were similar to WT mice.
CONCLUSIONS
CONCLUSIONS
PYY signaling through Y2R is not required for the normal appetite-suppressing and body weight-lowering effects of RYGB in this global knockout mouse model. Potential compensatory adaptations of PYY signaling through other receptor subtypes or other gut satiety hormones such as glucagon-like peptide-1 (GLP-1) remain to be investigated.
Identifiants
pubmed: 30857366
pii: nu11030585
doi: 10.3390/nu11030585
pmc: PMC6471341
pii:
doi:
Substances chimiques
Receptors, Gastrointestinal Hormone
0
peptide YY receptor
0
Peptide YY
106388-42-5
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK047348
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK105032
Pays : United States
Organisme : NIH HHS
ID : DK047348
Pays : United States
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