The neutrophil migration on kidney-liver axis in a diet-induced NASH zebrafish model

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a metabolic syndrome with high incidence in the population, especially in western society. Overfeeding and large portions of fatty meats, saturated fat, and low levels of fibers are associated with a higher risk of NAFLD. The increased consumption of industrialized food is also one of the main factors in unbalanced diets. In industrialized food, fructose is found as one of the main sweeteners used. With the increased number of patients with metabolic syndrome and consumption of fructose, understanding the metabolic effects of this sugar in the body became eessential. Fructose is absorbed into the cells of the intestine and liver by GLUT5 and GLUT2 transporters. However, when consumed in high portions, fructose is metabolized in other organs, such as kidney and adipose tissue. As a result of a rich fructose diet, there is an increased production of uric acid, proinflammatory factors, and body fat, all factors that can trigger NAFLD. One of the hallmarks of NAFLD is the imbalance of proinflammatory cytokines in the liver, with activation of T cell helper 1 and Kupffer cells with M1-like phenotype, as demonstrated in zebrafish. Moreover, the liver regulates lipoprotein metabolism and is capable of coordinating the metabolism and inflammation of the whole body. It is already known that there is a crosstalk between the liver and kidney. In that sense, the systemic inflammatory process of NAFLD overflows to the kidney through cytokines and immune cells. As it has already been demonstrated, the neutrophils migrate through the body from the liver, and after diet-induced-NASH, show an inflammatory profile that affects other tissues, such as the tail. In that sense, the migration of inflammatory neutrophils can inflict kidney injury. However, it is important to point out that fructose can generate inflammation directly in the kidney, once it can be absorbed in the tubular renal cells. Therefore, this project aims to understand the effects of high fructose intake in the NAFLD, and how this organ communicates with the kidney by migration of neutrophils. (AU)