Multi-organ systems study reveals Igfbp7 as a suppressor of gluconeogenesis after gastric bypass surgery

ABSTRACT: 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 glycemic profile remain largely unknown. We used the RYGB surgery model in diet-induced obese (DIO) mice to monitor the proteome (with tandem mass tagging) of the Roux and biliopancreatic limbs, the liver and the pancreas up to four weeks after surgery, a time window associated with the early beneficial metabolic effects of the RYGB surgery model. The resulting kinetics were analyzed using high-dimensional cluster analysis that we recently developed (XINA,PMID: 30370770) to infer co-regulated proteins and pathways based on common kinetic profiles. Our analysis revealed the organs exhibited unique and common changes to their proteomes reflecting their specialized physiological roles and potential coordinated inter-organ crosstalk and responses, respectively. Further exploration of the Roux limb proteome kinetics included the identification of relatively unknown proteins found with clusters comprising established protein-protein interaction networks. One such protein was insulin-like growth factor binding protein 7 (Igfbp7) whose subsequent in vitro and in vivo studies supported the role of this secreted protein in suppressing hepatic gluconeogenesis; which in turn, substantiates our systems approach to discover new mechanisms by which the RYGB surgery exerts beneficial effects.

INSTRUMENT(S): Orbitrap Fusion Lumos, Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Intestine, Liver, Pancreas

SUBMITTER: Sasha Singh  

LAB HEAD: Sasha Singh

PROVIDER: PXD015276 | Pride | 2020-01-23

REPOSITORIES: Pride