Effects mediated by the exercise and metformin on rock protein and the regulation of lipogenesis and glucose production in the liver of rodents with celiac disease

Abstract

Celiac disease (CD) is an autoimmune and multisystem gluten-related disorder that causes symptoms involving the gastrointestinal tract and other organs, including liver. In this context, some relationships have already established and pointed to the intestine-liver axis that has a close anatomical relationship and interconnected by portal circulation as a possible link between celiac disease and liver disease, since an intense immunological (inflammatory biomolecules) and metabolic processes between these two organs occur constantly. Also, the inflammatory process is known to be associated with insulin resistance, which induces increased lipolysis and increased targeting of free fatty acids to the liver, culminating in the accumulation of triacylglycerols in the hepatic tissue and later on the onset of non-alcoholic fatty liver disease (NAFLD). Moreover, insulin resistance favors increased hepatic glucose production (HGP), since insulin can suppress gluconeogenesis and glycogenolysis. Since the resistance to this hormone is still not fully understood, several studies have been conducted to identify new molecules with regulatory actions on insulin signaling pathways and consequently on glucose homeostasis (10). A Rho- kinase (Rock) is a serine/threonine kinase that is involved in various physiological functions, with negative effects on the insulin signaling pathway in the liver. In the order hand, it is very well known that physical exercise and metformin acts as important tools in the prevention and treatment of diabetes arising from obesity to collaborate in restoring insulin signaling in peripheral tissues, suppressing both exacerbated production hepatic glucose and lipogenesis. Therefore, in this study, our main objective is to investigate the effects of physical exercise and metformin on Rock protein and the signaling pathway of lipogenesis and gluconeogenesis in the liver of rodents with celiac disease. After defining the celiac disease model, the animals will undergo a physical training protocol (short period) or metformin treated to evaluate the effects on the lipogenesis and hepatic gluconeogenesis of the animals. Bioinformatics, histological, physiological and molecular biology analyzes will be performed in the different experimental groups. Data will be analyzed by Student t-test, comparing the two groups and an analysis of variance (ANOVA) test followed by Bonferroni multiple means, when appropriate, to compare control and experimental groups. The statistical significance will be set at p < 0.05. (AU)