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The role of gut-pancreas axis upon glycemic homeostasis maintenance in obese mice submitted to vertical gastrectomy: a molecular and functional approach

Grant number: 19/00728-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): November 01, 2019
Effective date (End): October 31, 2021
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Everardo Magalhães Carneiro
Grantee:Gabriela Moreira Soares
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:13/07607-8 - OCRC - Obesity and Comorbidities Research Center, AP.CEPID

Abstract

Obesity has reached pandemic proportions and it is associated with numerous complications, including insulin resistance and Type 2 Diabetes Mellitus. One of the mechanisms responsible for this relation is the systemic inflammatory state. Recently inflammatory and intestinal immune changes have been investigated as a link between Obesity and insulin resistance. Several strategies have been used in the treatment of Obesity and the inflammatory process, such as restrictive bariatric surgeries like the Vertical Gastrectomy (VG). VG has beneficial effects upon body weight and glucose metabolism in humans and animal experimental models, mediated in part by the increase in incretin concentration. This type of procedure influences pancreatic beta cell function and insulin secretion, an effect related to glucose homeostasis maintenance. However, still remains unclear how this new organic condition leads to a hormonal rearrangement of the gut-pancreas axis, resulting in changes in the levels of some hormones like FGF15/19, GLP-1 and insulin. In this context, the intestinal hormone FGF15/19 has emerged as a target, since it is related to the regulation of lipid and glucose metabolism. However, the molecular and functional mechanisms involved with the actions of FGF15/19 after bariatric surgery and its relation to glycemic homeostasis have not been explored. In this project, we propose to investigate the molecular and functional mechanisms associated with the beneficial effects of VG upon glycemic homeostasis, focusing on the role of gut-pancreas axis via FGF15/19. In addition, we aim to identify possible new molecules involved in this context, focusing on glycemic stability. (AU)