Banca de DEFESA: JHONY WILLAMS GUSMÃO DO NASCIMENTO

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : JHONY WILLAMS GUSMÃO DO NASCIMENTO
DATE: 03/11/2023
TIME: 09:00
LOCAL: Videoconferência
TITLE:

TREATMENT WITH LIRAGLUTIDE IN VITRO AND IN VIVO: CELLULAR EFFECTS, ON GASTROINTESTINAL MOTILITY AND ON THE INFLAMMATORY RESPONSE OF INTESTINAL EPITHELIAL TISSUE OF RATS.

KEY WORDS:

 Inflammation, Liraglutide, Cell Migration, Gastrointestinal Tract, Cell Viability.

PAGES: 50
BIG AREA: Ciências da Saúde
AREA: Medicina
SUBÁREA: Clínica Médica
SPECIALTY: Endocrinologia
SUMMARY:

Obesity is a chronic disease, characterized by a state of acute low-grade inflammation, which affects gastrointestinal permeability and motility, and the action of cytokines in this scenario is little reported. Liraglutide is a glucagon-like peptide-1 (GLP-1) analog that induces weight loss by different mechanisms involving the gastrointestinal tract. The objective of this study was to evaluate the effects of Liraglutide on intestinal epithelial cells in vitro and on metabolic, morpho-functional, and inflammatory parameters in the gastrointestinal tract of rats with obesity. Methods: In the in vitro assay, IEC-6 cells were treated with concentrations from 0.25 to 100 µM of Liraglutide and evaluated for cell viability, cell death by apoptosis and necrosis, morphological analysis, actin cytoskeletal reorganization and assay of cell migration for wound healing. In the in vivo assay, Wistar rats with obesity were randomly assigned to receive saline solution, 400 or 1200 µg Liraglutide/kg/day subcutaneously for 30 consecutive days, once a day. Weight gain, feed efficiency, caloric intake, gastric motility, adiposity, histomorphometric, murinometric, and biochemical parameters were evaluated before and after treatment. Results: There was no change in the viability of cells treated with Liraglutide at concentrations of 0.25, 0.5, and 1 μM; moreover, drug treatment decreased the rate of apoptosis of IEC-6 cells relative to control. Treated cells showed a modified actin cytoskeleton, with prominent stress fibers and decreased cell migration. The effects of Liraglutide in treated animals were dose-dependent. The dose of 1200 µg/day/kg provided lower feed efficiency and lower caloric intake, with slower gastric emptying and lower amplitude of gastric contractions. Gastrointestinal effects were accompanied by reductions in muscle layer thickness and crypt depth. Liraglutide reduced retroperitoneal and visceral adipose tissue deposits, decreased TNF-α levels, and increased TGF-β1 levels. There was a reduction in total cholesterol, triglycerides, and liver transaminases. Conclusion: Liraglutide directly affected intestinal cells, decreasing the rate of apoptosis, and the disposition of the actin cytoskeleton, reducing cell migration. In rats, it reduced fat accumulation, improved metabolic parameters, and minimized the expression of inflammatory signaling in the gastrointestinal tract.

COMMITTEE MEMBERS:
Presidente - ***.657.108-** - LUCIANA APARECIDA CORA - UNCISAL
Interno(a) - ***.641.864-** - GUILHERME BENJAMIN BRANDAO PITTA - UNCISAL
Externo(a) à Instituição - JOSE RICARDO DE ARRUDA MIRANDA - UNESP
Externo(a) à Instituição - EDOARDA VASCO DE ALBUQUERQUE ALBUQUERQUE
Externo(a) à Instituição - FERNANDO GOMES ROMEIRO - UNESP