Multiorgan Systems Study Reveals Igfbp7 as a Suppressor of Gluconeogenesis after Gastric Bypass Surgery.
bariatric surgery
diabetes
insulin-like growth factor binding protein 7
metabolic syndrome
obesity
protein−protein interactions
proteomics
tandem mass tagging
Journal
Journal of proteome research
ISSN: 1535-3907
Titre abrégé: J Proteome Res
Pays: United States
ID NLM: 101128775
Informations de publication
Date de publication:
03 01 2020
03 01 2020
Historique:
pubmed:
30
10
2019
medline:
22
6
2021
entrez:
30
10
2019
Statut:
ppublish
Résumé
Roux-en-Y gastric bypass (RYGB) surgery reduces weight in obese patients. A marked decrease in blood glucose levels occurs before weight loss; however, key molecules that improve the glycemic profile remain largely unknown. Using a murine RYGB surgery model, we performed multiorgan proteomics and bioinformatics to monitor the proteins and molecular pathways that change in this early glycemic response. Multiplexed proteomic kinetics data analysis revealed that the Roux limb, biliopancreatic limb, liver, and pancreas each exhibited unique temporal and molecular responses to the RYGB surgery. In addition, protein-protein network analysis indicated that the changes to the microbial environment in the intestine may play a crucial role in the beneficial effects of RYGB surgery. Furthermore, insulin-like growth factor binding protein 7 (Igfbp7) was identified as an early induced protein in the Roux limb. Known secretory properties of Igfbp7 prompted us to further investigate its role as a remote organ regulator of glucose metabolism. Igfbp7 overexpression decreased blood glucose levels in diet-induced obese mice and attenuated gluconeogenic gene expression in the liver. Secreted Igfbp7 appeared to mediate these beneficial effects. These results demonstrate that organs responded differentially to RYGB surgery and indicate that Igfbp7 may play an important role in improving blood glucose levels.
Identifiants
pubmed: 31661273
doi: 10.1021/acs.jproteome.9b00441
doi:
Substances chimiques
Blood Glucose
0
Insulin-Like Growth Factor Binding Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
129-143Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL126901
Pays : United States