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Evaluation of the relationship between obesity and ghrelin in a model of inflammation induced by LPS in vivo and in culture of peritoneal macrophages

Grant number: 20/04076-5
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): November 01, 2020
Effective date (End): January 31, 2022
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Angelita Maria Stabile
Grantee:Mariele Lenhari Gonçalves
Host Institution: Escola de Enfermagem de Ribeirão Preto (EERP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Sepsis is characterized by an unregulated immune response that can progress to septic shock, a condition with a greater chance of death. It is known that obesity can increase the risk of morbidities, favoring the occurrence of infectious diseases and sepsis. Ghrelin is an orexigenic hormone that has a lower plasma concentration in obese people and is known to exert regulatory actions in the inflammatory response. This hormone is an endogenous ligand for the GHS-R1a isoform of the growth hormone secretagogue receptor. It is suggested that ghrelin and the GHS-R1a receptor are expressed in macrophages, in addition to the treatment with exogenous ghrelin having anti-inflammatory effects on these cells. Thus, we suggest that ghrelin has an action in the regulation of the immune system during endotoxemia and that obesity reduces the expression of this hormone receptors in macrophages, exacerbating the proinflammatory response to the lipopolysaccharide (LPS) stimulus. Thus, the objective of the study is to evaluate the relationship between obesity and ghrelin in a model of inflammation induced by LPS in vivo and in culture of peritoneal macrophages. The animals will receive specific diets for 10 weeks; at the end of this period, the in vivo group will be treated with LPS or saline and will have blood and liver collected to assess the serum concentration of ghrelin and liver expression of GHS-R1a and INOS; in in vitro studies the macrophages will be treated with ghrelin and LPS and the concentrations of cytokines and nitrate in the culture medium will be evaluated, as well as the expression of iNOS, GHS-R1a and translocation of NF-kB by Western Blot. The data will be expressed as mean and standard error of the mean and statistical analysis will be performed using GraphPad Prism. Values will be considered significant when p <0.05.

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