Efeito da liraglutida na motilidade e na resposta inflamatória (TGF-β e TNF-ɑ) gastrintestinal em ratos obesos

Abstract

In obesity, the state of chronic low-grade inflammation appears to compromise gastrointestinal functions. Pharmacotherapy is commonly used in the treatment of obesity, although its gastrointestinal actions are poorly understood. The objective was to evaluate the effects of Liraglutide on gastrointestinal motility and on the inflammatory process in these tissues in obese rats. The obesity model adopted was the neonatal administration of monosodium glutamate (MSG) in male Wistar rats and the use of their obese descendants. These obese offspring and adults were treated with 400 μg/kg/day or 1200 μg/kg/day of liraglutide (Saxenda®, Novo Nordisk®, Brazil) or saline, subcutaneously, daily for 30 days. At the end of the experiment, feed intake and weight gain were determined, feces were collected, the oral glucose tolerance test (OGTT) was performed, and gastric emptying and contractility were recorded using Alternating Current Biosusceptometry (BAC). After death, materials were collected for serum biochemical analysis, dosage of tumor necrosis factor-alpha (TNF-α) and growth and transformation factor-beta (TGF-β) in duodenal tissue, gastrointestinal morphometry, adiposity index and weight relative of organs. Data were analyzed by ANOVA, followed by Dunett's post-test (p<0.05) or Kruskal Wallis followed by Dunn's (p <0.05). Treatment with liraglutide caused a significant reduction in weight gain, increased feed efficiency, body fat and provided liver protection and improved serum biochemical markers. At a dose of 1200 μg/kg/day, it led to a reduction in the thickness of the muscle layer and in the amplitude (dB) of gastric contractility, with consequent delay in gastric emptying time. Such effects may be associated with an increase in satiety due to the longer time the food remains in the stomach compared to the control group. The group treated with a higher dose of Liraglutide had a lower intestinal concentration of TNF-α (pg/mL) and a higher intestinal concentration of TGF-β1 (pg/mL) compared to the control group, indicating that the drug has local anti-inflammatory activity. Such alterations probably influenced the gastrointestinal motility and morphometry itself. It is concluded that liraglutide, in rats treated for thirty days with a dose of 1200 μg/kg/day, acts on the gastrointestinal tissue favoring the treatment of obesity not only through endocrine, but also immune and motor pathways.